Author Archives: Paul Cacciatore

ASCO 2011: Novel Multi-targeted Agent Cabozantinib (XL184) Has Significant Effect on Several Advanced Solid Tumors

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Cabozantinib (XL184) demonstrated high rates of disease control in patients with prostate, ovarian and liver cancers. The investigators concluded that cabozantinib exhibits clinical activity in ovarian cancer patients with advanced disease, regardless of prior platinum drug status, as reflected by the high rates of response. 

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a phase II clinical trial involving cabozantinib (XL184) were highlighted today in the ASCO press briefing, as summarized below.

Novel Multi-targeted Agent Cabozantinib (XL184) Has Significant Effect on Several Advanced Solid Tumors, and Can Shrink or Eliminate Bone Metastases 

Cabozantinib (XL184) – an oral inhibitor of MET and VEGFR2 kinases involved in the development and progression of many cancers – showed strong responses in patients with various advanced cancers in a phase II trial. The drug demonstrated particularly high rates of disease control for advanced prostate, ovarian and liver cancers, which are historically resistant to available therapies. The drug also fully or partially eliminated bone metastases in patients with breast and prostate cancers and melanoma.

Michael S. Gordon, M.D., President & Chief Executive Officer, Pinnacle Oncology Hematology.

“Cabozantinib appears to have significant effects on several treatment-resistant tumors, as well as impressive effects on bone metastases. In addition, these effects are associated with rapid improvement in pain, a reduction in opiate narcotic requirements and improvement in anemia,” said lead author Michael S. Gordon, M.D., a medical oncologist at Pinnacle Oncology Hematology located in Scottsdale, Arizona. “The implications of these results are very exciting—it is unusual to find a targeted therapy, absent of a molecular mutation in tumors, that works in bony disease and has this activity.”

To be eligible for the study, patients had to have advanced, progressive solid tumors, with or without bone metastases. Of 398 evaluable patients (of 483 enrolled in the trial), 39 percent had bone metastases at baseline. Patients received cabozantinib over 12 weeks. The trial was designed as a “discontinuation” trial, in which those who had partial responses stayed on the drug; those with stable disease were randomized to cabozantinib or placebo; and patients with progressive disease were removed from the trial. This novel type of clinical trial design more quickly evaluates the disease-stabilizing activity of growth-inhibitory agents like cabozantinib, compared to the traditional model of randomizing all patients to either the experimental arm or placebo.

Among 398 patients evaluable with all types of cancer included in the trial, the collective overall response rate was 9 percent (34 of 398). The highest disease control rates (partial response and stable disease) at week 12 were 76 percent for liver cancer (22 of 29 patients), 71 percent for prostate cancer (71 of 100 patients), and 58 percent for ovarian cancer (32 of 51 patients). [emphasis added].

Of the 51 evaluable ovarian cancer patients noted above, 28 are platinum drug resistant, 17 are platinum drug sensitive, and 6 have unknown status. The median number of systemic treatments prior to trial enrollment was 2. The overall response rate (complete response and partial response based on modified RECIST criteria) for ovarian cancer was 12/51 (24%).  Upon breakdown, the response rate was 5/28 (18%) for platinum drug resistant patients, and 5/17 (29%) for platinum drug sensitive patients. Five additional partial responses await confirmation. After a median follow-up of 4 months (range: 1 to 11 months), the median duration of response and median progression free survival have not been reached. The most common related adverse events ( ≥grade 3) among ovarian cancer patients were hand-foot syndrome (10%), diarrhea (8%) and fatigue (4%). Drug dose reductions and permanent discontinuations for adverse events occurred in 43% and 10% of the ovarian cancer patients, respectively. Based on these findings, the investigators concluded that cabozantinib exhibits clinical activity in ovarian cancer patients with advanced disease, regardless of prior platinum drug status, as reflected by the high rates of response. [emphasis added] Accordingly, randomization in the ovarian cancer cohort was halted & patients unblinded due to the observed high efficacy.

Fifty-nine of 68 patients with bone metastases (including patients with breast and prostate cancers and melanoma) experienced either partial or complete disappearance of the cancer on bone scans, often with significant pain relief and other improved cancer-related symptoms.

The reduction of bone metastases and pain relief was an unexpected finding in this study, Dr. Gordon said. Independent review by radiologists confirmed that bone metastases disappeared in the majority of patients who had bone metastases when they entered the study. The majority of these patients had castration-resistant prostate cancer (CRPC), but patients with breast cancer and melanoma also had disappearance of bone metastases. Bone metastases greatly contribute to morbidity and mortality in patients with these types of cancer, which typically spread to the bone.

Due to these results, the study has been expanded to include more CRPC patients. Similarly, the high rate of lasting responses in ovarian cancer patients led researchers to also expand the study to evaluate the drug’s effect on patients with a particularly resistant form of the disease known as platinum drug resistant/refractory ovarian cancer. [emphasis added]

This study expansion results will help determine the design of future phase III trials, which will assess whether the drug extends patients lives or has other longer-term benefits among patients with specific cancer types. At present, cabozantinib is being investigated for use as a single agent. Additional studies will evaluate the efficacy and tolerability of appropriate combinations with other agents for future indications.

For the solid tumor patients collectively, the most common grade three or above adverse events were fatigue (9 percent) and hand-foot syndrome (8 percent). Dose reductions were required in 41 percent of patients due to side effects; 12 percent were removed from the trial for adverse events.

Sources:

Resources:

Cabozantinib (XL184) Clinical Trials:

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ASCO 2011: Maintenance Therapy With PARP Inhibitors Could Play Important Role in Treatment of Recurrent Ovarian Cancer

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A randomized phase II clinical trial showed that the oral PARP inhibitor drug olaparib (AZD2281), given after chemotherapy, improved progression-free survival in women with the most common type of recurrent ovarian cancer.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a phase II clinical trial involving maintenance therapy with the PARP (poly (ADP-ribose) polymerase) inhibitor olaparib were highlighted today in the ASCO press briefing, as summarized below.

Randomized Study Shows that Maintenance Therapy With PARP Inhibitors Could Play Important Role in Treatment of Recurrent Ovarian Cancer

A phase II randomized trial showed that maintenance treatment with the oral PARP inhibitor drug olaparib (AZD2281) improved progression-free survival by about four months in women with the most common type of relapsed ovarian cancer. This is the first randomized trial to demonstrate a benefit for maintenance therapy for recurrent ovarian cancer, and the first randomized trial in ovarian cancer of a PARP inhibitor– a novel class of molecularly targeted drugs.

The results of this study, if confirmed in larger trials, could lead to a new treatment approach for recurrent ovarian cancer in which drugs like olaparib are given over a long period of time to prevent recurrences or prolong remissions. This somewhat novel approach, called maintenance therapy, has already proven useful in lung cancer. Standard treatment for ovarian cancer includes platinum-based chemotherapy. After this regimen, patients are observed until recurrence, and then treated with another course of chemotherapy. While some tumors respond well to chemotherapy, the regimens are too toxic for patients to take continuously, and clinical trials have not shown any benefit for extended courses of chemotherapy.

Jonathan A. Ledermann, M.D., Lead Author & Principal Investigator of PARP Maintenance Study; Professor, Medical Oncology, UCL Cancer Institute, University College London

“A well-tolerated antitumor agent that could be used for months or perhaps years as maintenance therapy after standard chemotherapy could be a big step forward and ultimately extend survival,” said lead author Jonathan A. Ledermann, M.D., principal investigator of the study and Professor of Medical Oncology at UCL Cancer Institute, University College London. “This study demonstrates proof of principle for the concept of maintenance therapy in ovarian cancer using a PARP inhibitor. Our progression-free survival difference was very impressive and better than we anticipated.”

The multicenter, international study randomized 265 women with high-grade serous ovarian cancer to either olaparib or placebo. Patients were enrolled in the trial within 8 weeks of having achieved either a complete or partial response to platinum-based treatment. PARP inhibitors have been shown to work better in patients whose tumors have responded to platinum.

In the study, the progression-free survival (PFS) – the amount of time during and after treatment in which the cancer does not return – was significantly longer in the group receiving olaparib than the placebo group, with a median of 8.4 months versus 4.8 months. At the time of data analysis, half the patients randomized to olaparib (68 patients) had not relapsed and were still receiving the drug, while only 16 percent (21 patients) remained on placebo – so overall survival data were not yet available for analysis.

Adverse events were more commonly reported in the group receiving olaparib than placebo, including nausea, fatigue, vomiting, and anemia, but the majority of these were not severe. Dose reductions to manage side effects were allowed in the study and were more prevalent in the olaparib group (23 percent) compared to the placebo group (7 percent).

Olaparib inhibits the enzyme poly (ADP-ribose) polymerase — abbreviated “PARP” — which is involved in DNA (deoxyribonucleic acid) repair. Up to half of women with high-grade serous ovarian cancer – the most common type of ovarian cancer – may have a DNA repair deficiency that makes them more susceptible to treatment with PARP inhibitors.

A number of PARP inhibitors are being studied in phase II and phase III clinical trials, as single agents and in combination with standard chemotherapies and radiation, in some types of breast and ovarian cancers believed to have DNA repair defects.

Sources:

PARP Clinical Trials:
Resources:
Related WORD of HOPE™ Ovarian Cancer Podcasts:
Related Libby’s H*O*P*E*™ Postings:
Related Libby’s H*O*P*E*™ Videos Re PARP Inhibitors


2011 ASCO: Screening With CA-125 & Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives

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Findings from a large, long-term study – the Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial – showed that using a CA-125 blood test and transvaginal ultrasound for early detection of ovarian cancer did not reduce the risk of dying from the disease, and resulted in a large number of false positives and related follow-up procedures.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Ill. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a large clinical trial involving ovarian cancer screening were highlighted in today’s press briefing as summarized below.

Screening with CA-125 and Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives

A randomized, multicenter screening study of nearly 80,000 women in the general population showed that using a CA-125 blood test and transvaginal ultrasound for early detection of ovarian cancer did not reduce the risk of dying from the disease, and resulted in a large number of false positives and related biopsies and follow-up procedures. The results indicate that while these tests are widely and appropriately used to evaluate symptoms, and to gauge disease status and effectiveness of treatment in women already diagnosed with ovarian cancer, they are not useful in screening the general population.

Saundra S. Buys, M.D., Medical Director, Huntsman Cancer Institute’s High Risk Breast Cancer Clinic; Professor, Depart. of Internal Medicine, Univ. of Utah School of Medicine

“There hasn’t been a good method for the early detection of ovarian cancer, and our hypothesis was that CA-125 and transvaginal ultrasound, which are useful in measuring disease, would also identify ovarian cancer early, at a stage in which it is more likely to be cured,” said lead author Saundra Buys, M.D., professor of medicine at the University of Utah and Huntsman Cancer Institute in Salt Lake City. “The results were disappointing, but not necessarily surprising. The study shows that the available tests are not effective and may actually cause harm because of the high number of false positives. These results point to the continued need for more precise and effective screening tools for this disease.”

In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 78,216 women ages 55 to 74 were assigned to either annual screening (39,105 women) or usual care (39,111 women) between 1993 and 2001. Women in the screening arm were offered annual CA-125 testing for six years and transvaginal ultrasound for four, and followed for up to 13 years. Those in the usual care arm were not offered the screening tests.

The results showed no statistically significant difference in ovarian cancer cases or mortality between the two arms. Ovarian cancer was diagnosed in 212 women in the screening group arm compared to 176 in the usual care arm; 118 women in the screening arm died from ovarian cancer, while 100 died from ovarian cancer in the usual care group.

Among women in the screening arm, there were a high number of false positives – 3,285 false positives, compared to just 212 true positives. Of women who had a false positive test, 1,080 underwent surgery for biopsy – the procedure generally required to evaluate positive test results; 163 of them had serious complications.

The authors emphasized that the study results don’t apply to screening women with symptoms or abnormal findings on physical examination. [emphasis added] Physical examination based on symptoms and appropriate follow-up testing remains the best available approach for ovarian cancer detection.

[Note: This summary contains updated data and a correction from the original abstract. Correction:  Of the 3,285 women who received a false positive exam, 1,080 underwent surgery. Of those surgical patients, 163 encountered at least one serious complication.]

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2011 ASCO Annual Meeting Abstracts (Including Ovarian Cancer) Made Publicly Available Today

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More than 30,000 cancer specialists from around the world will gather at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting to discuss the latest innovations in research, quality, practice and technology in cancer.

More than 30,000 cancer specialists from around the world will gather at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting to discuss the latest innovations in research, quality, practice and technology in cancer.

The meeting will be held June 3-7, 2011 at McCormick Place located in Chicago, Illinois. This meeting will be the platform for the release of thousands of scientific abstracts — highly anticipated research news for many people, including patients, caregivers, and the general public. Today, many of those abstracts were made publicly available online (see below).

The 2011 Annual Meeting will center on a theme of “Patients, Pathways, Progress.” The theme, which was selected by ASCO President George W. Sledge, Jr., M.D., promises to:

  • Represent “patients first,” said Dr. Sledge. “Everything we do as a Society has, as its eventual goal, the reduction of cancer mortality and morbidity. We’re on the front line in the war against cancer.”
  • Focus on the molecular, clinical and research pathways that are used to find, develop and implement new treatments for people living with cancer.
  • Celebrate the progress that has already been made in the treatment of cancer, while also reaffirming ASCO’s commitment to aggressive advancements in cancer research in the future.
News announced during the Annual Meeting will include the latest findings from cancer clinical trials, including new drug studies that could change current standards of care. ASCO shares this timely information with the public in a variety of ways. Free patient-friendly summaries of research news highlights from this year’s Annual Meeting will be available via ASCO’s patient information website, Cancer.Net (www.cancer.net). Cancer.Net will post scientific news as soon as it becomes publicly available, on both its homepage and its ASCO Annual Meetings section. The offerings on Cancer.Net include:
  • Easy-to-read summaries that put the top scientific news into context for patients.
  • Videos and podcasts of national and international cancer experts, breaking down the science into specific disease areas and explaining what the studies mean for people with cancer.
  • A news archive from previous ASCO Annual Meetings, which is searchable by year or disease type.

To receive ASCO Annual Meeting breaking news via email, you can sign up now to receive special editions of the newsletter Inside Cancer.Net. You can also follow Cancer.Net on Facebook or Twitter, where real-time updates will also be posted.

Medical abstracts from this year’s meeting were released today at 6:00 P.M. EDT/3:00 P.M. PDT, and additional studies will be released each day of the event in June.

The abstract categories released today, which may be of interest to an ovarian cancer survivor, include the following:

Cancer Prevention/Epidemiology

Developmental Therapeutics – Clinical Pharmacology and Immunotherapy

Gynecologic Cancer

2011 Pharmaceutical Research & Manufacturers of America Report Lists 58 Drugs in Development For Ovarian Cancer

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Currently, 851 medicines are in development for diseases that exclusively or disproportionately affect women, according to a report unveiled today by the Pharmaceutical Research and Manufacturers of America (PhRMA).

Currently, 851 medicines are in development for diseases that exclusively or disproportionately affect women, according to a report unveiled today by the Pharmaceutical Research and Manufacturers of America (PhRMA).  The medicines in the pipeline for women (either in human clinical trials or awaiting review by the Food and Drug Administration) include:

• 139 for cancers affecting women, including 91 for breast cancer, 49 for ovarian cancer,[1] and 9 for cervical cancer.

• 114 for arthritis/musculoskeletal disorders. Approximately 46 million Americans have some type of arthritis or related condition, and 60 percent of them are female.

• 64 for obstetric/gynecologic conditions.

• 110 for autoimmune diseases, which strike women three times more than men.

• 72 for depression and anxiety. Almost twice as many women as men suffer from these disorders.

• 83 for Alzheimer’s disease. Two-thirds (3.4 million) of the 5.4 million Americans living with Alzheimer’s today are women.

The Drug Discovery Process

Ovarian cancer affected an estimated 21,880 U.S. women in 2010 and caused an estimated 13,850 deaths.  The PhRMA report highlighted a potential first-in-class ovarian cancer drug (volasertib/BI 6727) in development which works by selectively inhibiting the polo-like kinase-1 (PLK-1), an enzyme crucial for cell division. PLK-1 is expressed in proliferating cells and most tumors. Inhibiting its activity disrupts cell division, which induces cell death and reduces cancer growth.

The ovarian cancer drugs listed in the PhRMA report are listed below by name (brand name, if available, and generic name), manufacturer, and phase of clinical testing. The ovarian cancer drugs listed in the “Cancer” section of the PhRMA report are set forth below:[2]

A6, Angstrom Pharmaceuticals, Phase II.

Abagovomab (anti-idiotype ovarian cancer vaccine)(Orphan Drug), Menarini, Phase I/II.

Abraxane®/albumin-bound paclitaxel, Celgene, Phase II.

ABT-888/veliparib, Abbott Laboratories, Phase II.

AE-37, Antigen Express, Phase I.

Afinitor®/everolimus, Novartis Pharmaceuticals, Phase I/II.

AMG 386, Amgen, Phase III.

AMG 479, Amgen, Phase II.

Avastin®, bevacizumab, Genentech, Phase III.

BC-819, BioCancell Therapeutics, Phase I/II.

Catumaxomab, Fresenius Biotech, Phase II.

CVac™/MUC-2 cancer vaccine, Prima BioMed, Phase II.

DCVax®-L/ovarian cancer vaccine, Northwest Biotherapeutics, Phase I.

DPX-0907, Immunovaccine, Phase I.

EC-145, Endocyte, Phase II.

EGEN-001 (Orphan Drug), EGEN, Phase I/II.

ENMD-2076, EntreMed, Phase II.

Estybon™/ON-01910.Na, Onconova Therapeutics, Phase II.

Evizon™/squalamine, OHR Pharmaceuticals, Phase II.

farletuzumab/MORAb-003, Eisai, Phase III.

iboctadekin, GlaxoSmithKline, Phase I.

IMT-1012/immunotherapeutic vaccine, Immunotope, Phase I.

iniparib/BSI-201, BiPar Sciences/sanofi-aventis, Phase II.

Karenitecin®/cositecan, BioNumerik Pharmaceuticals, Phase III.

KHK-2866, Kyowa Hakko Kirin Pharma, Phase I.

lenvatinib/E7080, Eisai, Phase II.

MK-2206, Merck, Phase I.

Nexavar®/sorafenib, Bayer HealthCare Pharmaceuticals/Onyx Pharmaceuticals, Phase II.

NKTR-102, Nektar Therapeutics, Phase II.

NOV-002, Novelos Therapeutics, Phase II.

OGX-427, Oncogenex Pharmaceuticals, Phase I.

olaparib/AZD2281, AstraZeneca, Phase II.

Opaxio™/paclitaxel poliglumex, Cell Therapeutics/Novartis Pharmaceuticals, Phase III.

Optisome™/topetecan liposomal, Talon Therapeutics, Phase I.

Oregovomab, Quest Pharmatech, Phase I/II.

OSI-906/linsitinib, OSI Pharmaceuticals, Phase II.

OVax®/ovarian cancer vaccine (Orphan Drug), AVAX Technologies, Phase I/II.

Perifosine/KRX-0401, AEterna Zentaris/Keryx Biopharmaceuticals, Phase I.

PF-01367338, Pfizer, Phase II.

Phenoxodiol (next generation drug will be NV-143), Marshall Edwards, Phase III.

Picoplatin intravenous, Poniard Pharmaceuticals, Phase II.

Quinamed®/amonafide, ChemGenex Pharmaceuticals, Phase II.

Ramucirumab/IMC-1121-B, Eli Lilly/ImClone, Phase I.

Ridaforolimus, Merck/Ariad Pharmaceuticals, Phase I.

Sagopilone, Bayer HealthCare Pharmaceuticals, Phase II.

SAR256212/MM-121, Merrimack Pharmaceuticals/sanofi-aventis, Phase I.

SG2000, Spirogen, Phase II.

Sprycel®/dasatinib, Bristol-Myers Squibb, Phase

Tarceva®/erlotinib, Genentech, Phase II.

Telcyta®/canfosfimide, Telik, Phase III.

Tigatuzumab, Daiichi Sankyo, Phase II.

Tykerb®/lapatinib, GlaxoSmithKline, Phase I/II.

Volasertib, Boehringer Ingelheim Pharmaceuticals, Phase II.

Volociximab, Bigen Idec/Facet Biotech, Phase II.

Vosaroxin™/SNS-595, Sunesis Pharmaceuticals, Phase II.

Votrient®/pazopanib, GlaxoSmithKline, Phase III.

Zolinza®/vorinostat, Merck, Phase II.

Zybrestat™/fosbretabulin, OXiGENE, Phase II.

References:

1/The 2011 PhRMA report lists 49 ovarian cancer drugs in development.  After comparing the entire “Cancer” drug list set forth on pages 16 – 24 of the PhRMA report to the ovarian cancer clinical trials provided at http://www.clinicaltrials.gov, we determined that an additional nine drugs appearing on the PhRMA cancer drug list are being tested in ovarian cancer clinical trials.

2/Please note that the PhRMA cancer drug list does not set forth all ovarian cancer drugs in development.  For a list of all open ovarian cancer clinical trials listed at www.clinicaltrials.gov, click here.

Sources:

Resources:

Blunting the Activity of Protein Abcc10 May Help Counter Taxane Drug Resistance In Ovarian Cancer

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New findings by Fox Chase Cancer Center researchers identify one protein, Abcc10, as being intimately involved in resistance to certain drugs used to treat breast, ovarian, lung, and other cancers. The results suggest that blunting the activity of Abcc10 might help counter resistance and extend the effectiveness of these anticancer drugs.

Today’s anticancer drugs often work wonders against malignancies, but sometimes tumors become resistant to the effects of such drugs, and treatment fails. Medical researchers would like to find ways of counteracting such resistance, but first they must understand why and how it happens. New findings by Fox Chase Cancer Center researchers identify one protein, Abcc10 (ATP-binding cassette transporter 10) (also known as multidrug resistance protein 7 (Mrp7)), as being intimately involved in resistance to certain drugs used to treat breast, ovarian, lung, and other cancers. The results suggest that blunting the activity of Abcc10 might help counter resistance and extend the effectiveness of these anticancer drugs.

The findings appear in the May 15, 2011 issue of the journal Cancer Research.

Elizabeth A. Hopper-Borge, Ph.D., Assistant Professor, Fox Chase Cancer Center, Philadelphia, Pennsylvania

In earlier work, Elizabeth A. Hopper-Borge, Ph.D., an assistant professor at Fox Chase, showed that Abcc10 confers resistance to a number of anticancer agents, particularly taxanes, which include paclitaxel (Taxol) and docetaxel (Taxotere). These drugs––originally derived from the Pacific yew tree––work by disrupting cell division, thus arresting the growth and spread of tumors. The initial finding that Abcc10, a member of a ubiquitous family of proteins called ATP-binding cassette transporters, thwarts taxanes’ anti-tumor activity was something of a surprise, says Hopper-Borge, because none of the other family members seem to have that ability.

In the new research, Hopper-Borge and colleagues wanted to further explore, in both cultured cells and mice, the role of Abcc10. They developed a “knockout” mouse, in which the gene that codes for Abcc10 was missing, or knocked out. These mice appeared normal and healthy in every other respect, suggesting that Abcc10 is not essential for overall health and survival.

The researchers isolated cells from the knockout mice and tested the cells’ reactions to taxanes and two other anticancer drugs, vincristine and Ara-C. Compared to cells from normal mice that still possessed the gene for Abcc10, the knockout mouse cells were much more sensitive to the drugs.

Abcc10 and its ilk work by pumping drugs out of cells, so one might expect to see the drugs accumulating in cells that lack Abcc10, and that’s exactly what Hopper-Borge’s group saw. It had been suggested that other proteins might take over for Abcc10 if that protein were knocked out, but the researchers found no evidence suggesting that had happened.

Next, the research team studied the effects of one particular taxane, paclitaxel, on mice and found that the knockout mice were more sensitive to the drug, as reflected in body weight, white blood cell count, and ability to survive escalating doses of the drug.

“After seeing the effects on white blood cells, we decided to look at the tissue types that produce white blood cells to see if we could actually see differences there,” says Hopper-Borge. As expected, knockout mice treated with paclitaxel had smaller spleens and thymus glands and underdeveloped bone marrow, compared to normal mice treated with the same drug.

The results provide the first evidence from living organisms that Abcc10 is a cell’s built-in protection against the effects of powerful drugs, and raises the possibility of using Abcc10 inhibitors to break down that resistance and sensitize tumor cells to anticancer agents. The fact that mice lacking the protein have no obvious health problems is encouraging, suggesting that Abcc10 inhibitors could be used in human patients without causing side effects that might be expected to result from interfering with the pump’s normal functions.

Several Abcc10 inhibitors already have been identified, but they also inhibit other cellular transporters, which could have deleterious effects. For that reason, Hopper-Borge thinks the best approach may be developing inhibitors that work only in tumor cells or coming up with compounds that modulate, rather than completely inhibit the protein’s activity.

But using such treatments in patients is still far in the future, she emphasizes.

“I’d like to stress that we did this work in a mouse model,” Hopper-Borge says. “Our results so far suggest that this protein may be a clinically relevant target, but we need to do more studies to find out for sure.”

Co-authors on the study include Timothy Churchill, Chelsy Paulose, Emmanuelle Nicolas, Joely D. Jacobs, Olivia Ngo, Andres J. Klein-Szanto and Martin G. Belinsky of Fox Chase; Yehong Kuang of Central South University, Changsha, China; Alex Grinberg and Heiner Westphal of the National Institute of Child Health and Human Development; and Gary D. Kruh of the University of Illinois at Chicago.

The research was supported by the National Institutes of Health.

Sources:

Libby’s H*O*P*E* & Women’s Oncology Research & Dialogue Launch New “WORD of HOPE™” Ovarian Cancer Educational Podcast Series

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WORD OF HOPE™ Ovarian Cancer Podcast Now Available Through New Website, iTunes, YouTube, and Other Online Sources.

A new ovarian cancer educational podcast series, entitled “WORD of HOPE™,” was launched during Women’s Health Awareness Week through a collaborative initiative of Libby’s H*O*P*E*™ (LH) and Women’s Oncology Research & Dialogue (WORD).

The WORD of HOPE™ Ovarian Cancer podcast series will address important topics related to ovarian cancer, including prevention, early detection, diagnosis, groundbreaking treatments, scientific and clinical research information, and related women’s health information for ovarian cancer patients, caregivers and advocates. The WORD of HOPE™ podcast series can be found online at http://www.wordofhopepodcast.com, and is available to viewers and listeners for subscription at the WORD Of HOPE™ podcast website, iTunes, and YouTube.

“From the beginning, WORD has been committed to taking the most important scientific information and providing patients, caregivers and advocates the easily accessible resources to educate and inspire during their journey of care. As a physician, nearly every day we are looking for resources to give newly diagnosed patients and their supporters to help them better understand their diagnosis and treatment options. We are proud to partner with Libby’s H*O*P*E*™ and its founder Paul Cacciatore in the production of these new podcasts,” said Dr. John Geisler, WORD co-founder and Director of Gynecologic Oncology at University of Toledo.

Paul Cacciatore, Libby’s H*O*P*E* founder and podcast co-host said: “The WORD of HOPE™ ovarian cancer podcast series embodies the age old adage that ‘information is power’ — a potentially life-saving concept in the fight against the most lethal gynecologic cancer.” Mr. Cacciatore emphasized that the information featured in the podcast series is easy to understand and accessible from anywhere, including at home, on the job, or on the go through a smartphone or iPad. “WORD of HOPE™ not only raises much-needed ovarian cancer awareness in the minds of the general public, it educates survivors to proactively participate in their treatment through more meaningful dialogue with their doctors. Libby’s H*O*P*E* is proud to partner with WORD through this global form of social media.”

The first podcast installment will feature the following seven episodes (three already posted; four pending) which address ten significant 2010 scientific research and clinical treatment topics within the field of ovarian cancer:

Viewers or listeners of WORD of HOPE™ Ovarian Cancer Podcast can contact Nathan Manahan, WORD Executive Director, via email to provide feedback and ideas for the podcast. To listen, watch or subscribe to the podcast series, visit http://www.wordofhopepodcast.com.

About the WORD of HOPE™ Podcast

Based in Indianapolis, Indiana (WORD) and Los Angeles, California (LH), WORD of HOPE™ serves viewers and listeners interested in up-to-date ovarian cancer information. Hosted by Nathan Manahan and Paul Cacciatore, WORD of HOPE™ ovarian cancer podcasts will be released several times a month and available for subscription through iTunes, RSS and YouTube.

About Women’s Oncology Research & Dialogue

Co-founded by gynecologic oncologists Drs. Kelly Manahan and John Geisler, WORD is an Indianapolis-based nonprofit organization dedicated to helping women conquer gynecologic cancers through catalyzing innovative scientific and clinical research, which results in empowering educational resources for women’s organizations and medical personnel regarding proper prevention, diagnosis and treatment.

About Libby’s H*O*P*E*™

Paul Cacciatore established Libby’s H*O*P*E*(*Helping *Ovarian Cancer Survivors *Persevere Through *Education)™ in March 2008 as an online resource to assist his 26-year-old cousin, Elizabeth “Libby” Remick, who was battling advanced-stage ovarian cancer. Although Libby ultimately lost her battle to the disease, Paul continues to assist ovarian cancer survivors worldwide, and their families and friends, through the website under the principle that “information is power” in the fight against ovarian cancer. Through Libby’s H*O*P*E*™, Paul has published approximately 250 weblog articles relating to ovarian cancer and cancer-related topics. Libby’s H*O*P*E*™ utilizes a variety of online media resources and social networks to disseminate critical information relating to ovarian cancer awareness, including the early warning signs and symptoms of the disease, important medical discoveries, relevant current clinical trials, and most importantly, stories of hope involving ovarian cancer survivors and their families. To learn more, visit https://healthinfoispower.wordpress.com

For more information, contact Executive Producer, Chad Braham at 317-855-8144 or visit the official website: http://www.wordofhopepodcast.com.

OVA1 Blood Test Detects Ovarian Cancer In Women With A Known Ovarian Mass More Accurately Than CA-125

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A study published online in Obstetrics & Gynecology reports that the OVA1 blood test detects ovarian cancer in women with a previously discovered ovarian mass more accurately than the CA-125 blood test. The study also considers OVA1’s place in future surgical referral guidelines.

A study published online ahead of print in the June 2011 edition of Obstetrics & Gynecology demonstrated that American College of Obstetrics and Gynecology (ACOG) guidelines for determining the likelihood that an ovarian mass is cancerous prior to surgery would accurately identify more women with ovarian cancer if the OVA1 blood test were used in place of the currently recommended CA-125 (cancer antigen 125) blood test. The study builds on prior research that shows accurate assessment of an ovarian mass for cancer prior to surgery can affect both treatment decisions and health outcomes for women with ovarian cancer.

… When OVA1 was used in place of CA 125 as recommend in the [ACOG] guidelines, 94% of malignancies in women of all ages in the study were accurately detected compared to 77% with CA-125. In addition, OVA1 improved sensitivity in premenopausal women, accurately detecting 91% of women with ovarian cancer in fewer than 58% with CA125. … The study also showed that the OVA1 test was about two times more likely to incorrectly identify women as high risk for ovarian cancer when they were not (a “false positive“) as compared to the CA-125 test overall. … 

OVA1 is the first test cleared by the U.S. Food and Drug Administration (FDA) for aiding in the pre-surgical evaluation of a woman’s ovarian mass for cancer. Vermillion, Inc., a molecular diagnostics company, developed OVA1, and Quest Diagnostics Incorporated, the world’s leading diagnostic testing company, offers OVA1 testing services in the United States and India. Quest Diagnostics and Vermillion both participated in the study and Vermillion also helped fund the study. Neither company had any involvement in the development of the manuscript.

Clinical practice guidelines recommend that women with ovarian cancer be under the care of a gynecologic oncologist, although only an estimated one-third of initial surgeries for ovarian cancer are performed by these specialists. ACOG guidelines for the management of ovarian masses recommend that physicians evaluate several factors, including menopausal status, imaging findings, family history, and CA 125 blood test levels, to divide women into low- and high-risk categories on which treatment plans, including surgical referral, are based.

The study evaluated the performance of the ACOG guidelines using the CA-125 test versus the OVA1 test in 516 women scheduled for surgery for an ovarian mass across a diverse group of primary and specialty care centers. When OVA1 was used in place of CA-125 as recommend in the guidelines, 94% of malignancies in women of all ages in the study were accurately detected compared to 77% with CA 125. In addition, OVA1 improved sensitivity in premenopausal women, accurately detecting 91% of women with ovarian cancer in fewer than 58% with CA-125.

Rachel Ware Miller, M.D., Assistant Professor, Gynecologic Oncology, Markey Cancer Center, University of Kentucky

“The high sensitivity in premenopausal women and early stage cancers is where CA-125 and the College guidelines have underperformed,” wrote investigator Rachel Ware Miller, M.D., assistant professor gynecologic oncology at the University of Kentucky’s Markey Cancer Center, in the study. ” Identifying these patients for referral is valuable because many are not receiving appropriate surgical staging and treatment. An effective preoperative test, particularly for younger women and early-stage cancers, can have a favorable effect on women’s health as survival is better in these populations.”

OVA1 when used with the College guidelines was also effective at detecting advanced disease, when surgery and chemotherapy can “improve overall survival,” wrote Dr. Miller.

The study also showed that the OVA1 test was about two times more likely to incorrectly identify women as high risk for ovarian cancer when they were not (a “false positive“), as compared to the CA-125 test overall. However, as OVA1 is only indicated for women for whom surgery is already planned, a higher rate of false positives would increase the possibility that a woman’s surgery is performed by a gynecologic oncologist rather than a gynecologist or other non-specialist.

The study follows the March 2011 publication in Obstetrics & Gynecology, the official publication of ACOG, of an updated committee opinion, The Role Of The Obstetrician-Gynecologist In The Early Detection Of Epithelial Ovarian Cancer, by ACOG and Society of Gynecologic Oncologists (SGO) that cited the FDA clearance of OVA1 (in 2009) and indicated that OVA1 “appears to improve the predictability of ovarian cancer in women with pelvic masses” and “may be useful for evaluating women with a pelvic mass.”

“Prior to OVA1’s clearance by the FDA, the only lab test physicians could use to assess the likelihood that an ovarian mass was malignant prior to surgery was CA-125, even though CA-125 is not indicated for this use and its performance is variable,” said Dr. Eric T. Fung, chief science officer, Vermillion, Inc. “These data should give physicians more confidence to refer women whose OVA1 test result indicates a high likelihood of cancer to a gynecologic oncologist for surgery.”

Ovarian cancer is the leading cause of death from gynecologic cancers in the United States and the fifth-leading cause of cancer deaths in women. Ovarian masses affect an estimated one million women and lead to as many 300,000 ovarian mass surgeries in the United States each year, according to an analysis by third parties on behalf of Quest Diagnostics.

About OVA1®

OVA1 is the first test cleared by FDA for aiding in the pre-surgical evaluation of a woman’s ovarian mass for cancer, and also is the first protein-based In Vitro Diagnostic Multi-Variate Index Assays (IVDMIA), a new class of state of the art software-based diagnostics. The test utilizes five well-established biomarkers — transthyretin (TT or prealbumin), apoolipoprotein A-1 (Apo A-1), beta 2-microglobulin (beta 2M), transferrin (Tfr) and cancer antigen 125 (CA-125 II) — and proprietary software to determine the likelihood of malignancy in women with ovarian mass for whom surgery is planned.

OVA1 is indicated for women who meet the following criteria: (i) over age 18, (ii) ovarian adnexal mass present for which surgery is planned, and (iii) not yet referred to an oncologist. It is an aid to further assess the likelihood that malignancy is present when the physician’s independent clinical and radiological evaluation does not indicate malignancy. The test should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of the OVA1 Test carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.

About Quest Diagnostics

Quest Diagnostics is the world’s leading provider of diagnostic testing, information and services that patients and doctors need to make better healthcare decisions. The company offers the broadest access to diagnostic testing services through its network of laboratories and patient service centers, and provides interpretive consultation through its extensive medical and scientific staff. Quest Diagnostics is a pioneer in developing innovative diagnostic tests and advanced healthcare information technology solutions that help improve patient care. Additional company information is available at http://www.questdiagnostics.com/.

About Vermillion, Inc.

Vermillion, Inc. is dedicated to the development and commercialization of novel high-value diagnostic tests that help physicians diagnose, treat and improve outcomes for patients. Vermillion, along with its prestigious scientific collaborators, has diagnostic programs in oncology, cardiology and women’s health. Additional information about Vermillion can be found on the Web at http://www.vermillion.com/.

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Experimental Drug NVP-BEZ235 Slows Ovarian Cancer Growth in Mice; Solid Tumor Clinical Trials Ongoing

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A study conducted recently at UCLA’s Jonsson Comprehensive Cancer Center found that experimental drug NVP-BEZ235, which blocks two points of a crucial cancer cell signaling pathway, inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model.

A study conducted recently at  UCLA’s Jonsson Comprehensive Cancer Center (JCCC) found that an experimental drug, which blocks two points of a crucial cancer cell signaling pathway, inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model.

Oliver Dorigo, M.D., Ph.D., Assistant Professor, Department of Gynecologic Oncology, Division Gynecologic Oncology, UCLA Jonnson Comprehensive Cancer Center; Member, JCCC Cancer Molecular Imaging Program Area

The Novartis Oncology drug, called NVP-BEZ235, also inhibits growth of ovarian cancer cells that have become resistant to the conventional treatment with platinum chemotherapy and helps to resensitize the cancer cells to the therapy. In addition, it enhances the effect of platinum chemotherapy on ovarian cancer cells that are still responding to the therapy, said the study’s senior author, Dr. Oliver Dorigo, an assistant professor of obstetrics and gynecology and a JCCC researcher.

“Platinum-based chemotherapy drugs are effective in treating ovarian cancers as long as the cancer cells remain sensitive to platinum,” Dorigo said. “But once the tumor becomes resistant, treating the cancer becomes very challenging. This is a significant clinical problem, since the majority of ovarian cancer patients develop resistance at some point during treatment. Breaking chemotherapy resistance is a difficult challenge, but crucial if we want to improve long-term survival for our patients.”

The study, performed on cells lines and mouse models, appears in the April 15 issue of the journal Clinical Cancer Research.

Over the last several years, Dorigo has been working in his laboratory to develop new therapies for ovarian cancer. About 22,000 American women are diagnosed each year with ovarian cancer, and more than 14,000 deaths are attributed to the disease annually. Dorigo has focused his research efforts on a pathway called PI3Kinase/Akt/mTOR, which, once activated, promotes ovarian cancer growth. The activated pathway also makes the cancer more aggressive and more likely to spread to other organs, Dorigo said, so targeting it offers great promise for more effective therapies for the disease.

In this two-year study, Dorigo and postdoctoral fellow Chintda Santiskulvong found that inhibiting two checkpoints of the pathway — PI3Kinase and mTOR — with NVP-BEZ235 decreased cancer growth, both in cell culture dishes and in mice with ovarian cancer. It also significantly increased survival in the mice, he said. More importantly, NVP-BEZ235 slowed growth of the ovarian cancer cells that had become resistant to platinum and helped to break that resistance.

“We were very encouraged to find that NPV-BEZ235 could resensitize the ovarian cancer cells to standard platinum treatment,” Dorigo said. “In addition, we found this drug to be more effective in inhibiting ovarian cancer cell growth than other drugs that target only one checkpoint, mTOR, in this pathway. We believe that NVP-BEZ235 has superior efficacy because of the dual effect on PI3Kinase and mTOR.”

The experimental drug is being tested as a single agent at the Jonsson Cancer Center in human clinical trials against other solid tumors. Researchers involved with those studies have said early results are encouraging.

John Glaspy, M.D., M.P.H., Co-Chief, Department of Medicine, Hematology/Oncology, UCLA Jonnson Comprehensive Cancer Center; JCCC Director, JCCC Clinical Research Unit; Member, Stand Up To Cancer Mangement Committee

“This is clearly a promising agent with activity in humans,” said Dr. John Glaspy, a professor of hematology–oncology and a Jonsson Cancer Center scientist involved with the studies. “We are still assessing its tolerability in patients.”

Dorigo said he hopes to initiate a clinical trial for women with ovarian cancer that tests the combination of NVP-BEZ235 with platinum chemotherapy, as he believes that the combination might be more effective than each drug alone.

The study was funded by the Ovarian Cancer Research Foundation/Liz Tilberis Scholarship, the Gynecologic Cancer Foundation/Florence and Marshall Schwid Ovarian Cancer Award, a STOP Cancer Career Development Award and the National Institutes of Health’s Women’s Reproductive Health Research Program.

About the UCLA Jonnson Comprehensive Cancer Center

UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2010, the center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 of the last 11 years.

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Clinical Trial Information:

U.K. NICE Issues New Clinical Guidelines Re Recognition & Initial Management of Ovarian Cancer

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On April 27, 2011, the U.K. National Institute For Health and Clinical Excellence issued new clinical guidelines regarding the recognition and initial management of ovarian cancer.

On April 27, 2011, the U.K. National Institute For Health and Clinical Excellence (NICE) issued new clinical guidelines regarding the recognition and initial management of ovarian cancer.

In the first ever clinical guideline for ovarian cancer, NICE is calling for more initial investigations to take place in primary care settings, such as general practice (GP) surgeries, so that women can be referred to hospital specialists sooner and begin treatment. This guidance updates and replaces recommendation 1.7.4 in Referral guidelines for suspected cancer (NICE clinical guideline 27; published 2005).

NICE also produced a series of tools to help U.K. healthcare professionals put this new guidance into practice, including guidance documents for doctors and patients, podcasts, clinical case scenarios and a slide set. To view a complete list of all NICE-produced guidance materials available to doctors and patients, visit http://guidance.nice.org.uk/CG122.

The full text NICE ovarian cancer clinical guidelines are classified under the following six chapter headings:

  • Epidemiology
  • Detection in Primary Care
  • Establishing the Diagnosis in Primary Care
  • Management of Suspected Early (stage I) Ovarian Cancer
  • Management of Advanced (stage II-IV) Ovarian Cancer
  • Support Needs of Women With Newly Diagnosed Ovarian Cancer

The key priorities identified by NICE for successful implementation of the new ovarian cancer clinical guidelines by primary and secondary healthcare professionals include the topics addressed below.

Awareness of Symptoms & Signs

— Carry out tests in primary care if a woman (especially if 50 or over) reports having any of the following symptoms on a persistent or frequent basis – particularly more than 12 times per month:

  • persistent abdominal distension (women often refer to this as “bloating”);
  • feeling full (early satiety) and/or loss of appetite;
  • pelvic or abdominal pain; and/or
  • increased urinary urgency and/or frequency.

— Carry out appropriate tests for ovarian cancer in any woman of 50 or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS), because IBS rarely presents for the first time in women of this age.

Asking the Right Question – First Tests

— Measure serum CA125 in primary care in women with symptoms that suggest ovarian cancer.

— If serum CA125 is 35 IU/ml or greater, arrange an ultrasound scan of the abdomen and pelvis.

— For any woman who has normal serum CA125 (less than 35 IU/ml), or CA125 of 35 IU/ml or greater but a normal ultrasound:

  • assess her carefully for other clinical causes of her symptoms and investigate if appropriate; and
  • if no other clinical cause is apparent, advise her to return to her general practitioner (GP) if her symptoms become more frequent and/or persistent.

Malignancy Indices

— Calculate a risk of malignancy index I (RMI I) score (after performing an ultrasound) and refer all women with an RMI I score of 250 or greater to a specialist multidisciplinary team.

— Risk of malignancy index I (RMI I): RMI I is a product of the ultrasound scan score (U), menopausal status (M) and serum CA125 level.

— RMI I = U x M x  CA125

  • The ultrasound result is scored 1 point for each of the following characteristics: multilocular cysts, solid areas, metastases, ascites, and bilateral lesions. U = 0 for an ultrasound score of 0 points, U = 1 for an ultrasound score of 1 point, U = 3 for an ultrasound score of 2–5 points.
  • Menopausal status is scored as 1 = pre-menopausal and 3 = post-menopausal. The classification of “post-menopausal” is a woman who has had no period for more than 1 year or a woman over 50 who has had a hysterectomy.
  • Serum CA125 is measured in IU/ml.

Tissue Diagnosis

— If offering cytotoxic chemotherapy to women with suspected advanced ovarian cancer, first obtain a confirmed tissue diagnosis by histology (or by cytology if histology is not appropriate) in all but exceptional cases.

The Role of Systematic Retroperitoneal Lymphadenectomy

— Do not include systematic retroperitoneal lymphadenectomy (block dissection of lymph nodes from the pelvic side walls to the level of the renal veins) as part of standard surgical treatment in women with suspected ovarian cancer whose disease appears to be confined to the ovaries (that is, who appear to have stage I disease).

Adjuvant Systemic Chemotherapy For Stage I Disease

— Do not offer adjuvant chemotherapy to women who have had optimal surgical staging and have low-risk stage I disease ([tumor] grade 1 or 2, stage Ia or Ib).

Support Needs of Women with Newly Diagnosed Ovarian Cancer

— Offer all women with newly diagnosed ovarian cancer information about their disease, including psychosocial and psychosexual issues, that:

  • is available at the time they want it;
  • includes the amount of detail that they want and are able to deal with; and
  • is in a suitable format, including written information.

Source:  Ovarian cancer: the recognition and initial management of ovarian cancer (CG122), Full Guideline, National Institute For Health & Clinical Excellence (NICE), U.K. National Health Service (NHS), April 2011.

Additional Information:

2011 AACR Annual Meeting: Select Ovarian Cancer Presentations & Abstracts Available Online

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The 102nd American Association For Cancer Research (AACR) Annual Meeting will be held from Saturday, April 2 through Wednesday, April 6, 2011, at the Orange County Convention Center located in Orlando, Florida.  Select ovarian cancer presentations and abstracts are available online.

The 102nd American Association For Cancer Research (AACR) Annual Meeting will be held from Saturday, April 2 through Wednesday, April 6, 2011, at the Orange County Convention Center located in Orlando, Florida.  Select ovarian cancer meeting presentations and abstracts are now available online.

Once again, the AACR will host and organize an exciting program on the best and latest in cancer research, in which a large cross section of the cancer research community will participate, to advance the cause of treating and preventing cancer. The meeting program not only reflects the AACR’s strengths in basic, translational, and clinical research, but also emphasizes the productive interfaces emerging between these once-separated disciplines. The program also captures the advances on all of these fronts, with a range of speakers and participants who are leaders in research: cancer mechanisms, systems approaches to cancer biology, diagnostics and therapeutics, translation of advances to the clinic, and cutting-edge science in the prevention and early interception of cancer.

In advance of the actual meeting, you can review select ovarian cancer meeting and poster presentations that relate to basic, clinical, epidemiological, and translational research.

To view all available ovarian cancer meeting and poster presentations, CLICK HERE, and then click the “advanced search button,” and under “Abstract Organ Site,” choose “gynecological cancer:  ovarian cancer,” then click “search” at the top or bottom of the page .

To view a list of all available AACR program ovarian cancer-related webcasts available during and/or after the meeting, CLICK HERE and (i) type in “ovarian cancer” in the search box; (ii) choose “sessions (with details)” under the “Browse By” menu at the top of the page; and (iii) choose only “2011” within the  search filter (i.e., uncheck conference years 2004 – 2010), then click “Update Filter.” (note: you can also search for free and/or paid webcasts by using the search filter on this page).

Libby’s H*O*P*E*™ will post newsworthy ovarian cancer information that is disclosed during the course of the AACR Annual Meeting.

About the American Association For Cancer Research

The mission of the American Association for Cancer Research is to prevent and cure cancer. AACR was founded in 1907 by a group of 11 physicians and scientists interested in research “to further the investigation and spread the knowledge of cancer.” The AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries.

The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. Including Cancer Discovery, the AACR publishes seven major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. AACR journals represented 20 percent of the market share of total citations in 2009. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists.

Phenoxodiol Used In Combination With Platinum or Taxane-Based Chemotherapy Is Active In Platinum & Taxane-Resistant Ovarian Cancer

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Phase II clinical study results suggests phenoxodiol is active in platinum and taxane drug-resistant ovarian cancer patients when administered intravenously in combination with platinum or taxane-based chemotherapy

Marshall Edwards, Inc., an oncology company focused on the clinical development of novel therapeutics targeting cancer metabolism, recently announced the publication of results from a phase II clinical trial of intravenous phenoxodiol in combination with cisplatin or paclitaxel in women with platinum–refractory/resistant ovarian cancer. The publication is now available on the International Journal of Gynecological Cancer website, and the print edition will appear the May issue of the journal.

The study, conducted at Yale-New Haven Hospital, showed that the combination of intravenous phenoxodiol, a novel NADH oxidase inhibitor, with cisplatin (a platinum-based chemotherapy) or paclitaxel (a taxane-based chemotherapy), was well tolerated.

Robert D. Mass, M.D., Acting Chief Medical Officer, Marshall Edwards.

In the study, 32 patients were randomized to one of two treatment arms according to their previous treatment responses: (1) platinum refractory/resistant patients received weekly cisplatin (40 mg/m intravenous), combined with weekly phenoxodiol (3 mg/kg); and (2) taxane refractory/resistant patients received weekly paclitaxel (80 mg/m intravenous), combined with weekly phenoxodiol (3 mg/kg). The study patients continued on treatment until complete response, disease progression, unacceptable toxicity, or voluntary withdrawal.

In the cisplatin study arm, there were 3 partial responses, 9 patients (56%) achieved stable disease, 4 patients (25%) progressed, and the overall best response rate was 19%. In the paclitaxel study arm, there was one complete response and 2 partial responses, 8 patients (53%) achieved stable disease, 4 patients (27%) progressed, and the overall best response rate was 20%. Response rate in this study was defined as the percentage of patients whose tumor demonstrated a radiologically confirmed reduction or disappearance after treatment.

There were no treatment-related deaths in the study, and there was only one treatment-related hospitalization and two grade 4 (i.e., life-threatening or disabling) adverse events.

Based upon the foregoing results, the researchers concluded that the combination of intravenous phenoxodiol with cisplatin or paclitaxel was well tolerated.  Moreover, the researchers stated that the cisplatin-phenoxodiol combination was particularly active and warrants further study in patients with platinum-resistant ovarian cancer.

“These results suggest that the combination of intravenous phenoxodiol with cisplatin has a good safety profile and may be capable of reversing resistance to platinum-based chemotherapy,” said lead author Michael G. Kelly, M.D., a gynecologic oncologist at Tufts Medical Center and former fellow at Yale University School of Medicine.” This study provides early clinical proof-of-concept for the combination of NADH oxidase inhibitors with standard-of-care chemotherapy and lays the groundwork for the development of more potent next-generation compounds.”

To date, phenoxodiol, an investigational drug, has been introduced into more than 400 patients in multiple clinical trials via oral or intravenous routes and has been well tolerated. Marshall Edwards has identified a next-generation compound called “NV-143,” which has demonstrated significantly more activity than phenoxodiol against a broad range of tumor cell lines. In addition to being more active as a single agent, NV-143 appears to be superior in its ability to synergize with platinum-based chemotherapy in pre-clinical studies. As a result, Marshall Edwards plans to initiate a phase I clinical trial of intravenous NV-143 later this year, followed immediately thereafter by randomized phase II trials in combination with chemotherapy.

“These published results combined with data from previous studies reinforce our conclusion that intravenous administration is the optimal route of delivery for this class of drugs and give us added confidence moving forward as we develop our next-generation compound NV-143 for the clinic,” said Robert D. Mass, M.D., Acting Chief Medical Officer of Marshall Edwards.

About Marshall Edwards

Marshall Edwards, Inc. is a San Diego-based oncology company focused on the clinical development of novel anti-cancer therapeutics. The Company’s lead programs focus on two families of small molecules that result in the inhibition of tumor cell metabolism. The first and most advanced is a NADH oxidase inhibitor program that includes lead drug candidate NV-143. The second is a mitochondrial inhibitor program that includes NV-128 and its next-generation candidate NV-344. Both programs are expected to advance into the clinic in 2011. For more information, visit www.marshalledwardsinc.com.

About Novogen Limited

Novogen Limited is an Australian biotechnology company based in Sydney, Australia. Novogen has a consumer healthcare business, and conducts research and development on oncology therapeutics through its 71.3% owned subsidiary, Marshall Edwards, Inc.

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Therapeutic Response To The Angiogenesis Inhibitor Sunitinib In Ovarian Clear Cell Cancer

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A group of international researchers reported sustained responses in two ovarian clear cell cancer (OCCC) patients with chemotherapy-resistant disease, who were treated with the anti-angiogenesis inhibitor sunitinib (Sutent®). The researchers emphasize the growing realization that OCCC is molecularly and clinically distinct as compared to other forms of ovarian cancer, and note significant common scientific characteristics possessed by both OCCC and renal clear cell cancer.

Clear Cell Carcinoma of the Ovary

Ovarian clear cell cancer (OCCC) is a rare form or subtype of epithelial ovarian cancer that is generally refractory to platinum-based chemotherapy. A group of international researchers from the United Kingdom, Australia, Japan, Canada and the United States recently reported results from comprehensive OCCC tumor gene expression and copy number testing, which was designed to identify potential therapeutic targets of OCCC.

Gene expression and DNA copy number testing was performed using primary human OCCC tumor samples, and the test findings were confirmed by immunohistochemistry (IHC) on tissue microarrays. Based on this testing, the researchers identified specific over-expression of the IL6 (interleukin-6)-STAT3 (signal transducer and activator of transcription 3)-HIF (hypoxia-inducible factors) cellular pathway in OCCC tumors, as compared with high-grade serous ovarian cancers. Expression of PTHLH (parathyroid hormone-like hormone) and high levels of circulating IL6 were also found in OCCC patients, and the researchers believe that this finding may explain the frequent occurrence of hypercalcemia and thromboembolic events in OCCC. Notably, the study results set forth a description of amplification of several RTKs (receptor tyrosine kinases), most notably MET (met proto-oncogene [hepatocyte growth factor receptor]), which certainly suggests other potential therapeutic targets for this hard-to-treat subtype of ovarian cancer.

Circulating IL6 levels were measured in the blood serum from patients with OCCC or high-grade serous ovarian cancers and corresponded to progression-free and overall survival. Two OCCC patients were treated with sunitinib and their therapeutic responses were measured clinically and by positron emission tomography (PET). The researchers reported sustained clinical and functional imaging responses in two OCCC patients with chemotherapy-resistant disease who were treated with sunitinib, thereby showing  significant scientific parallels with renal clear cell cancer.

Based upon the findings above, the researchers highlighted the importance of specific therapeutic targets in the treatment of OCCC, and suggested that more extensive clinical trials with sunitinib in OCCC patients are warranted.  The overarching findings of this study provide significant impetus to the growing realization that OCCC is molecularly and clinically distinct as compared to other forms of ovarian cancer.

Source: Anglesio MS, George J, Kulbe H, et. al. IL6-STAT3-HIF Signalling and Therapeutic Response To The Angiogenesis Inhibitor, Sunitinib, In Ovarian Clear Cell Cancer. Clin Cancer Res. 2011 Feb 22. [Epub ahead of print] PubMed PMID: 21343371.

Additional Information:

  • Dedicated Ovarian Clear Cell Cancer Clinical Trials (currently recruiting as of 3/25/11).

A Phase II Evaluation of SU11248 (Sunitinib Malate) (IND #74019, NSC #736511) in the Treatment of Persistent or Recurrent Clear Cell Ovarian Carcinoma, Clinical Trial Summary, NCT00979992, ClinicalTrials.gov.

A Phase II Evaluation of Temsirolimus (CCI-779) [Torisel®] (NCI Supplied Agent: NSC# 683864, IND# 61010) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus (CCI-779) Consolidation as First-Line Therapy in the Treatment of Stage III-IV Clear Cell Carcinoma of the Ovary, Clinical Trial Summary, NCT01196429, ClinicalTrials.gov.

  • Open Ovarian Cancer and Solid Tumor Clinical Trials Testing MET Inhibitors (as of 3/25/11)

We provide below a list of MET inhibitors that are currently available through open ovarian cancer and solid tumor clinical trials.  A few caveats are noteworthy.

First, the association between MET inhibiton and ovarian clear cell cancer inhibition has NOT been established as a form of treatment in large randomized, prospective clinical trials.

Second, most of the clinical trials listed below are phase I studies designed to test the biological activity and safety of the drug — not the effectiveness.  Patients enrolled in a phase I trial are generally the first humans to receive the study drug.

Third, all patients should seek advice from their doctor in advance of deciding to enroll in a clinical trial. Many of the clinical drugs listed below inhibit one or more cellular functions in addition to MET.

List of open solid tumor clinical trials testing AMG 208.

List of open solid tumor clinical trials testing MGCD-265.

List of open solid tumor clinical trials testing PF-2341066 (crizotinib)(NCT01121588 & NCT00585195).

List of open ovarian cancer clinical trials testing sunitinib (SU11274)/Sutent®.

List of open solid tumor clinical trials testing sunitinib (SU11274)/Sutent®.

List of open solid tumor clinical trials testing cabozantinib (a/k/a XL184 or BMS-907351).

List of open solid tumor clinical trials testing ARQ197.

List of open solid tumor clinical trials testing INCB28060.

List of open solid tumor clinical trials testing E7050.

List of open solid tumor clinical trials testing MGCD265.

  • Genetic Similarity Between Ovarian Clear Cell Cancer & Renal Clear Cell Cancer

Yoshida S, Furukawa N, Haruta S, et. al. Theoretical model of treatment strategies for clear cell carcinoma of the ovary: focus on perspectives. Cancer Treat Rev. 2009 Nov;35(7):608-15. Epub 2009 Aug 8. Review. PubMed PMID: 19665848.

Rauh-Hain JA, Penson RT. Potential benefit of Sunitinib in recurrent and refractory ovarian clear cell adenocarcinoma. Int J Gynecol Cancer. 2008 Sep-Oct;18(5):934-6. Epub 2007 Dec 13. PubMed PMID: 18081793.

Zorn KK, Bonome T, Gangi L, et. al. Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res. 2005 Sep 15;11(18):6422-30. PubMed PMID: 16166416.

“If You Are Lucky Enough To Be Irish, Then You Are Lucky Enough”

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Based on the Irish saying set forth above, I am certainly lucky enough — at least half of me is, on my mom’s side of the family.

All things Irish in celebration of St. Patrick's Day. (Photo: ShannonPatrick17)

Based on the Irish saying set forth above, I am certainly lucky enough — at least half of me is, on my mom’s side of the family.  For those of you who were “lucky enough” to be raised by one or two Irish parents, you know what I’m talking about — faith, family, cultural pride, education (Notre Dame, of course), food and drink (with an emphasis on drink), and good old fashion storytelling.

May the blessings of each day be the blessings you need most. — Irish proverb

My mother and one of my best friends (and former college roommate) provided me with my formal education of all things Irish. In fact, when we were in college, my roommate Sean referred to St. Patrick’s Day as the “holiest of holy days” — needless to say, nothing has changed since college.  He considers himself to be “very lucky” because he was raised by two Irish parents. In fact, Sean is so Irish that he founded a highly successful Irish dancing school in 1997 called, The Culkin School of Traditional Irish Dance, which is located in the Washington, D.C. area. Sean’s students have performed at many famous venues, including The John F. Kennedy Center for the Performing Arts.

Stephen: [looking to the sky] Alright, Father, I’ll ask him. …

Hamish: Is your father a ghost, or do you converse with the Almighty?

Stephen: In order to find his equal, an Irishman is forced to talk to God.

— Dialogue from the movie Braveheart (1995 Academy Award-Winning Best Picture).

If you live in an Irish household, today will likely involve a few traditions such as wearing green (bonus points for wearing a lapel pin with an image of a shamrock, Irish flag, or leprechaun); eating corned beef, cabbage, and soda bread; and drinking Guinness stout.  If you know nothing of Ireland, you can “fake it till you make it,” by going to a local Irish pub, or by learning a few fun facts related to St. Patrick’s Day and Irish Americans.

  • St. Patrick’s Day is celebrated on March 17, his religious feast day and the anniversary of his death in the 5th century. The Irish have observed this day as a religious holiday for over a thousand years.
  • The shamrock, which was also called the “seamroy” by the Celts, was a sacred plant in ancient Ireland because it symbolized the rebirth of spring.  By the 17th century, the shamrock had become a symbol of emerging Irish nationalism.
  • Music is often associated with St. Patrick’s Day and Irish culture in general. From the ancient days of the Celts, music has always been an important part of Irish life. The Celts had an oral culture, where religion, legend and history were passed from one generation to the next by way of stories and songs.
  • It has long been recounted that during his mission in Ireland, St. Patrick once stood on a hilltop (which is now called Croagh Patrick) with only a wooden staff by his side, and banished all the snakes from the island. In fact, the island nation was never home to any snakes. The “banishing of the snakes” was really a metaphor for the eradication of pagan ideology from Ireland and the triumph of Christianity. Within 200 years of Patrick’s arrival, Ireland was completely Christianized.
  • In 1959, Walt Disney released a film called Darby O’Gill & the Little People, which introduced America to a very different sort of leprechaun, as compared to the cantankerous little man of Irish folklore. This cheerful, friendly leprechaun is a purely American invention, but has quickly evolved into an easily recognizable symbol of both St. Patrick’s Day and Ireland in general.
  • Though cabbage has long been an Irish food, corned beef only began to be associated with St. Patrick’s Day at the turn of the 20th century. Irish immigrants living on New York City’s Lower East Side substituted corned beef for their traditional dish of Irish bacon to save money.
  • The Irish are not required to be Boston Celtics fans — go with a winner and side with the Los Angeles Lakers. (Sorry, that’s commentary rather than fact!)
  • When the Great Potato Famine hit Ireland in 1845, close to a million poor and uneducated Irish Catholics began pouring into the U.S. to escape starvation.
  • There are 36.9 million U.S. residents with Irish roots. This number is more than eight times the population of Ireland itself (4.5 million).
  • Across the U.S., 12 percent of residents lay claim to Irish ancestry. That number doubles to 24 percent in the state of Massachusetts.
  • The first St. Patrick’s Day parade took place in the U.S., not in Ireland. Irish soldiers serving in the English military marched through New York City on March 17, 1762.
  • The New York City St. Patrick’s Day Parade is the world’s oldest civilian parade and the largest in the U.S., with over 150,000 participants.
  • Chicago is famous for a somewhat peculiar St. Patrick’s Day annual event: dyeing the Chicago River green. The tradition started in 1962, when city pollution-control workers used dyes to trace illegal sewage discharges and realized that the green dye might provide a unique way to celebrate the holiday. That year, they released 100 pounds of green vegetable dye into the river—enough to keep it green for a week!  Today, in order to minimize environmental damage, only 40 pounds of dye are used, making the river green for only several hours.

I would like to take this opportunity to wish my mom (and her sisters) and the Culkin family all the best on this special day.  At Libby’s H*O*P*E*, we also wish you and yours a Happy St. Patrick’s Day.

May you always walk in sunshine. May you never want for more. May Irish angels rest their wings right beside your door.

–Irish Blessing

In the tradition of Irish music on St. Patrick’s Day, we leave you with a song by the Irish-American band Flogging Molly, entitled If I Ever Leave This World Alive.  This song is dedicated to those women who have lost their battle to ovarian cancer, but who inspire us to continue the fight for, and support of, ovarian cancer survivors and their families.

If I Ever Leave This World Alive, by Flogging Molly

2011 NCCN Conference: New Treatment Options Lead to Steady Progress Against Ovarian Cancer

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Recommendations stemming from recent clinical trials highlight notable updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for Ovarian Cancer at the National Comprehensive Cancer Network® (NCCN®) 16th Annual Conference.

Robert J. Morgan, Jr., M.D., Professor of Medical Oncology, City of Hope Comprehensive Cancer Center; Chair, NCCN Guidelines Panel for Ovarian Cancer

Although finding effective screening tools remains a priority, new treatment options for women with ovarian cancer, such as the ones outlined in the updated NCCN Guidelines for Ovarian Cancer,[1] are vital to making steady progress against the disease according to Robert J. Morgan, Jr., M.D., of City of Hope Comprehensive Cancer Center and chair of the NCCN Guidelines Panel for Ovarian Cancer. Dr. Morgan outlined significant updates to the NCCN Guidelines during a recent presentation at the NCCN 16th Annual Conference.

The NCCN Guidelines address epithelial ovarian cancer (including borderline or low malignant potential) and less common histopathologies, including malignant germ neoplasms, carcinosarcomas, and sex cord-stromal tumors. They also discuss fallopian tube cancer and primary peritoneal cancer, which are less common neoplasms that are managed in a similar manner to epithelial ovarian cancer.

“Regardless of the type of cancer, the NCCN Guidelines for Ovarian Cancer reflect the importance of stage and grade of disease on prognosis and treatment recommendations,” said Dr. Morgan.

The NCCN Guidelines continue to recommend that women with borderline epithelial ovarian cancer of low malignant potential be primarily surgically managed. In contrast to patients with frankly invasive ovarian carcinoma, women with borderline disease tend to be younger and are often diagnosed with stage I disease.

“The benefits of postoperative chemotherapy has not been demonstrated for patients who have no microscopically demonstrable invasive implants, said Dr. Morgan. “Even patients with advanced stage disease at presentation have an excellent prognosis and chemotherapy should be avoided.”

The NCCN Guidelines recommend surgery limited to a unilateral salpingo-oophorectomy (USO) (preserving the uterus and contralateral ovary) for women who wish to maintain their fertility, and standard ovarian cancer debulking surgery is recommended for those not concerned about fertility preservation.

On the contrary, in women diagnosed with stage II, III, or IV epithelial ovarian cancer, the NCCN Guidelines recommend intraperitoneal chemotherapy for first-line therapy and have been updated to include dose-dense paclitaxel (Taxol®:, Bristol-Myers Squibb) as a possible treatment option.

Dr. Morgan noted that in a recent clinical trial, dose-dense weekly paclitaxel with carboplatin (Paraplatin®:, Bristol-Myers Squibb) showed an increase in both progression-free survival and overall survival when compared with conventional intraperitoneal chemotherapy of weekly carboplatin/paclitaxel.[2]

“However, the dose-dense regimen is more toxic, and patients discontinued dose-dense paclitaxel therapy more often than those receiving standard therapy,” stated Dr. Morgan. “As with all treatment decisions, the patient needs to weigh the potential benefits and risks and discuss them thoroughly with their physician.”

Dr. Morgan discussed two additional phase 3 trials assessing bevacizumab (Avastin®:, Genentech/Roche) combined with carboplatin/paclitaxel in the upfront setting compared to carboplatin/paclitaxel alone.[3-4] Although data regarding overall survival and quality of life have not been reported yet, the studies did indicate that the median progression-free survival increased in patients receiving bevacizumab as a first line and maintenance therapy.

“Only modest improvements in progression-free survival were observed in both of these trials. The NCCN Guidelines Panel prefers to await mature results of these trials prior to recommending the routine addition of bevacizumab to carboplatin/paclitaxel,” said Dr. Morgan.

As such, the updated NCCN Guidelines includes new language detailing the Panel’s view on bevacizumab encouraging participation in ongoing clinical trials that are further investigating the role of anti-angiogenesis agents in the treatment of ovarian cancer, both in the upfront and recurrence settings.

Biomarkers continue to emerge as an area of interest in predicting future patterns of the disease. In patients with ovarian cancer, Dr. Morgan discussed the value of monitoring CA-125 levels in regards to a recent study[5] comparing early versus delayed treatment of relapsed ovarian cancer.

“Often, levels of CA-125 have been shown to rise prior to a clinical or symptomatic relapse in women with ovarian cancer. This trial looked at whether there was a benefit of early treatment on the basis of increased CA-125 concentrations compared with delayed treatment on the basis of clinical recurrence,” said Dr. Morgan.

The study, which was published in The Lancet, found that there was no survival benefit to early institution of treatment based on increased CA-125 levels and that the quality of life was superior in patients in the late treatment arm.

“The results of the trial suggest that the utility of the routine monitoring of CA-125 levels in limited,” said Dr. Morgan. “The NCCN Guidelines Panel encourages patients and their physicians to actively discuss the pros and cons of CA-125 monitoring based upon these findings and have updated the NCCN Guidelines to include language supporting this recommendation.”

Virtually all drugs used in oncology have the potential to cause adverse drug reactions while being infused, which can be classified as either infusion or allergic reactions. Recently, hypersensitivity to platinum compounds has been recognized as a potential issue for patients being administered these compounds.

“Platinum compounds remain very important in the treatment of ovarian cancer in both the upfront and recurrence settings, so it was important to design strategies to allow for the safe desensitization of these agents in patients who develop allergies,” said Dr. Morgan.

Standard desensitization regimens include slowly increasing infusion concentrations over several hours. However, Dr. Morgan noted that these procedures must be done in a specific manner in order to be safely administered and pointed to the recommendations within the updated NCCN Guidelines discussing the management of drug reactions.

In conclusion, Dr. Morgan emphasized that although steady progress is being made in the treatment of ovarian cancer, further trials are necessary to investigate the role of targeted agents alone and in combination in newly diagnosed and recurrent ovarian cancer. In addition, enrollment of patients with ovarian cancer must be encouraged.

The NCCN Guidelines are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of expert physicians from NCCN Member Institutions. The most recent version of this and all NCCN Guidelines are available free of charge at NCCN.org. The NCCN Guidelines for Patients™: Ovarian Cancer is available at NCCN.com.

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives. For more information, visit NCCN.org.

The NCCN Member Institutions are:

  • City of Hope Comprehensive Cancer Center
  • Dana-Farber/Brigham and Women’s Cancer Center
  • Massachusetts General Hospital Cancer Center
  • Duke Cancer Institute
  • Fox Chase Cancer Center
  • Huntsman Cancer Institute at the University of Utah
  • Fred Hutchinson Cancer Research Center / Seattle Cancer Care Alliance
  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Memorial Sloan-Kettering Cancer Center
  • H. Lee Moffitt Cancer Center & Research Institute
  • The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute
  • Roswell Park Cancer Institute
  • Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
  • St. Jude Children’s Research Hospital / University of Tennessee Cancer Institute
  • Stanford Comprehensive Cancer Center
  • University of Alabama at Birmingham Comprehensive Cancer Center
  • UCSF Helen Diller Family Comprehensive Cancer Center
  • University of Michigan Comprehensive Cancer Center
  • UNMC Eppley Cancer Center at The Nebraska Medical Center
  • The University of Texas MD Anderson Cancer Center
  • Vanderbilt-Ingram Cancer Center

References:

1/ Ovarian Cancer Including Fallopian Tube Cancer & Primary Peritoneal Cancer, Version 2.2011, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™), National Comprehensive Cancer Network. [PDF Adobe Reader Document – requires free registration and log-in at NCCN.org]

2/ Katsumata N, Yasuda M, Takahashi F, et. al. Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. Epub 2009 Sep 18. PubMed PMID: 19767092.

3/ Burger RA, Brady MF, Bookman MA, et. al.  Phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC):  a Gynecologic Oncology Group study.  J Clin Oncol 28:18s, 2010 (suppl; abstr LBA1).

4/ Perren T, Swart AM, Pfisterer J, et. al. ICON7: A phase III randomized gynecologic cancer intergroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab, versus chemotherapy alone in women with newly diagnosed epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC).Ann Oncol 21;viii2, 2010 (suppl 8; abstr LBA4).

5/Rustin G, van der Burg M, Griffin C, et. al. Early versus delayed treatment of relapsed ovarian cancer. Lancet. 2011 Jan 29;377(9763):380-1. PubMed PMID: 21277438.

Source:

Additional 2011 NCCN Annual Meeting Information