2008 ASCO Annual Meeting Abtracts Highlight Several Drugs That Show Promise Against Drug Resistant Ovarian Cancer

There were several drugs highlighted in clinical trial abstracts presented at the 2008 American Society of Clinical Oncology (ASCO) Annual Meeting that demonstrated varying degrees of effectiveness against drug resistant (i.e., recurrence within 6 to 12 months after completion of first line treatment) and/or drug refractory (i.e., recurrence within 6 months after completion of first line treatment) ovarian cancer. By “effectiveness,” we mean generally that the drug or drug combination produced a complete response, partial response, and/or disease stabilization (and in a few cases, a significant drop in the CA-125 tumor marker) in ovarian cancer tumors. To better understand how to intrepret a medical study abstract, click here. The 2008 ASCO Annual Meeting was held in Chicago, Illinois on May 30 – June 3, 2008.

A list of the drugs/drug combinations is provided below. Any drug covered in depth through an earlier H*O*P*E*™ weblog post is noted. We also included 2008 ASCO Annual Meeting abstracts that provide “solid tumor” clinical trial results with respect to studies that enrolled patients with ovarian cancer tumors. When evaluating the potential enrollment in a clinical trial at various treatment points, an ovarian cancer survivor should evaluate trials dedicated to ovarian cancer patients in entirety, as well as general “solid tumor” trials that allow enrollment of ovarian cancer patients. Generally, a patient should give first priority to dedicated ovarian cancer trials and use the solid tumor trials as a “backup” to the ovarian cancer trials. All questions regarding the priority assigned to, or proper sequencing of, clinical trials should be discussed in detail with your doctor(s). Treatment priority and sequencing issues arise, for example, when enrollment in one clinical trial potentially disqualifies the patient for a subsequent second clinical trial based upon the protocol (i.e., inclusion/exclusion criteria) of the second trial. This example assumes that both clinical trials are currently enrolling patients when trial enrollment is being evaluated by you and your doctor.

Abbreviation Legend:

ABSTR=2008 American Society of Clinical Oncology Annual Meeting Abtract; ASCO=American Society of Clinical Oncology; CA-125=cancer antigen 125; CEA=Carcinoembryonic Antigen (Tumor Marker); CR=Complete Response; CT=Computed Tomography

CTC=Common Toxicity Criteria; DCE-MRI=Dynamic Contrast Enhanced Magnetic Resonance Imaging; DLT=Dose Limiting Toxicity; DP=Disease Progression; EOC=Epithelial Ovarian Cancer; G=Grade of Adverse Drug Effect;

GCIG=Gynecologic Cancer Intergroup; GOGGynecologic Oncology Group; MTD=Maximum Tolerable Dose; mg/m²=milligrams per metre squared; NCI=National Cancer Institute; OR=Objective Response; OS=Overall Survival;

PET=Positron Emission Tomography Scanning; PK=Pharmacokinetics; PO=Oral Administration; PR=Partial Response; PFS=Progression Free Survival; RECIST=Response Evaluation Criteria in Solid Tumors; RR=Response Rate; SD=Stable Disease

SNS-595 (Voreloxin®):

NOV-002 & Carboplatin (Paraplatin®):

  • NOV-002 plus carboplatin in platinum-resistant ovarian cancer (2008 ASCO Abstract #5593). Patients were heavily pretreated with 11/15 patients having received 3 prior [treatment] lines. Toxicity was mild-moderate with no G4 toxicity. There was no febrile neutropenia. The most common toxicities were nausea and fatigue, as well as abdominal pain and bowel obstruction thought to be related to underlying disease. To date, there is 1 patient with PR, 7 patients with SD and 5 patients with PD, with 1 patient off-trial for patient discretion. PFS is 14 weeks. Patients tolerated this regimen extremely well, with most toxicity attributable to carboplatin alone. Conclusion: The PFS was longer than expected, with a significant proportion of these platinum resistant patients achieving clinical benefit with prolonged stable disease. [61% disease control (CR+PR+SD) rate]

Picoplatin & Pegylated Liposomal Doxorubicin (Doxil®):

  • Final results of a phase I study of picoplatin and pegylated liposomal doxorubicin [e.g. Doxil™] in advanced solid tumor malignancies (2008 ASCO Annual Mtg. Abstr. #2568 ): Picoplatin is a novel, sterically hindered platinum(II) complex designed to circumvent mechanisms of platinum resistance. Given the single agent activity seen in multiple tumor types, we conducted a phase I study of picoplatin in combination with pegylated liposomal doxorubicin (PLD) in patients with advanced solid tumors. The Phase 1 trial enrolled 16 patients with advanced solid tumors who had received up to three prior regimens for metastatic disease. Patients were administered picoplatin followed by liposomal doxorubicin on day one of a 28-day cycle. Four dose levels of picoplatin and pegylated liposomal doxorubicin were tested: 100/20, 100/30, 100/40 and 120/40 (all mg/m2). A total of 62 courses of treatment were delivered to 16 patients with a median number of four cycles per patient. A total of 12 patients were evaluable for response. One patient experienced a CR (primary peritoneal cancer) and four experienced a PR (including three of five patients with ovarian cancer). Hematologic and non-hematologic toxicity were mild. Conclusion: This study suggests that picoplatin and liposomal doxorubicin is an active combination with promising results and can be given at standard dose levels with a minimal increase in toxicity. [41% disease control (CR+PR+SD) rate among evaluable patients]

Weekly Topotecan (Hycamtin™) Monotherapy:

  • Phase II study of weekly topotecan in recurrent ovarian cancer: duration of response based on a prolonged follow-up (ASCO Annual Mtg. Abstr. #16549). Nineteen patients (median age 52 yrs, range 45-72) with EOC who progressed after 3 (11/19 patients = 57.9%), 4 (7/19 patients= 36.8%) or 5 (1/19 patients= 5.3%) previous lines of chemotherapy were treated with Topotecan at the dose of 2.0 mg/m2 via a 30-minute intravenous infusion once every week until disease progression, unacceptable toxicity or when a stability of disease was reached. Results: All patients were evaluable for toxicity and clinical response. 16/19 patients enrolled (84.2%) had stage III-IV disease. Median number of chemotherapy cycles was 7 (range 3 – 12). A total of 107 cycles were administered. Dose reduction was necessary for 13% of the cycles. Main toxicities included anemia (G1-G2=57.9%), leucopenia (G1-G2=15.8%), thrombocytopenia (G1-G2=10.5%) and asthenia (20%). No one showed a CR, while 5/19 patients experienced a PR (26.4%), 6/19 patients experienced SD (31.5%), and 8/19 patients (42.1%) experienced DP. The median PFS was 12 weeks in patients with PR; SD was maintained for a median time of 14 weeks. Conclusion: The rate of patients with ongoing stable disease (31.5%) suggests that the clinical benefit of weekly topotecan may be expected also in patients with no other viable therapeutic options. [57% disease control (CR+PR+SD) rate among evaluable patients]

Azacitidine & Carboplatin:

Combretastatin A4 Phosphate (Zybrestat™) and Bevacizumab (Avastin™):

BSI-201:

Belinostat (PXD101):

SU11248/Sunitinib (Sutent®):

AZD2281 (KU-0059436):

  • AZD2281, a PARP (poly ADP-ribose polymerase) inhibitor with single agent anticancer activity in patients with BRCA deficient ovarian cancer: Results from a phase I study (2008 ASCO Annual Mtg. Abstr. #5510) Thirty-two patients with BRCA-deficient ovarian cancer (i.e., patients with BRCA gene mutations) the majority of whom were platinum resistant/refractory are so far evaluable for response. All evaluable patients had either received treatment for at least 8 weeks (2 cycles) or progressed prior to completion of 2 cycles. Fourteen patients have achieved PR, 13 patients meeting GCIG- CA125 criteria and 10 patients meeting RECIST criteria. Of the responders, 1 patient has been on drug > 56 weeks whilst 7 patients have maintained responses for > 24 weeks. SD was seen in an additional 8 patients, 7 of whom continue on drug and 3 patients had SD > 16 weeks. Responses were seen at all dose levels from 100mg bd and above. Conclusion: AZD2281 is well tolerated and has demonstrated compelling activity in patients with BRCA deficient ovarian cancer. Responses were seen in all patient groups including platinum resistant disease. Updated efficacy data, together with a correlation of potential predictive factors including platinum free interval will be presented on a total planned cohort of 46 patients with BRCA-deficient ovarian cancer. A randomised study in BRCA-deficient ovarian cancer has been planned. [68% disease control (CR+PR+SD) rate among evaluable patients]

Gemcitibine (Gemzar™) & Epirubicin (Ellence™):

Belinostat/PXD101, Carboplatin (Paraplatin®) & Paclitaxel (Taxol™):

Pegylated Liposomal Doxorubicin (Doxil®) & Gemcitabine (Gemzar®):

Pemetrexed/LY231514 (Altima®):

Sorafenib (Nexavar™):

  • Phase II trial of sorafenib in persistent or recurrent epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC): A Gynecologic Oncology Group (GOG) study (2008 ASCO Annual Mtg. Abstr. #5537). Sorafenib is a tyrosine kinase inhibitor targeting raf and other receptor kinases (VEGF-R, PDGF-R, Flt3, c-KIT). Sorafenib may have anti-angiogenic activity through inhibition of VEGF-R. This phase II study was conducted to assess the activity and tolerability of sorafenib in patients with recurrent EOC. Methods: This was an open label multi-institutional phase II study …. Eligible patients had persistent or recurrent EOC/PPC after 1-2 prior cytotoxic regimens, measurable or detectable (e.g. by CA125) disease, and GOG performance status < 2. Patients were required to have progressed within 12 months of completing platinum based therapy. Treatment consisted of sorafenib 400 mg orally bid until disease progression or prohibitive toxicity. Primary endpoints were PFS at 6 months and toxicity by NCI criteria. Secondary endpoints were tumor response and duration of PFS/OS. Results: 73 patients were enrolled from 10/04 to 5/07 and as of 12/2007, 68 patients are evaluable (2 ineligible and 3 too early) for toxicity. Median age was 60 (range 33-80) years and prior treatment consisted of 1 regimen in 40 patients and 2 regimens in 28 patients. Significant G3 and G4 toxicities included: rash (12 patients), metabolic (10 patients), gastrointestinal (3 patients), cardiovascular (2 patients), and pulmonary (2 patients). No treatment related deaths were recorded. Only patients with measurable disease were used to assess efficacy. Among the 59 patients with measurable disease, 12 survived PFS at least 6 months. Three patients are yet to be determined. Two patients had PR; 20 had SD; 30 had DP, and 7 could not have their tumor assessed. Conclusions: Preliminary results suggest that sorafenib is tolerated in patients with recurrent EOC with dermatologic and metabolic abnormalities being the most common toxicities. Efficacy data is expected to reach maturity and be analyzed in the spring of 2007, and comprehensive results will be presented. [42% disease control (CR+PR+SD) rate among evaluable patients]

Topotecan (Hycamtin™) & Bevacizumab (Avastin™):

  • Phase II prospective study of weekly topotecan and bevacizumab in platinum refractory ovarian cancer or peritoneal cancer (OC) (2008 ASCO Annual Mtg. Abstr. #5551). Patients (pts) with platinum refractory OC have limited treatment options. Bevacizumab, an anti-angiogenesis agent has demonstrated efficacy in recurrent ovarian cancer. Bevacizumab combined with chemotherapy in other solid tumors has improved efficacy compared with bevacizumab or chemotherapy alone. Topotecan, an active drug in recurrent OC has been used in a weekly fashion with less toxicity and more acceptability than a standard 5 day regimen. Topotecan and bevacizumab have non-overlapping toxicities. We studied the efficacy and tolerability of weekly topotecan and bevacizumab in patients with platinum refractory OC. Methods: The primary objectives of this study were to evaluate PFS, OS, OR rate and toxicity of this combination regimen. Eligible pts included those with platinum refractory OC (recurrence < 6 months of platinum therapy) who had received a maximum of 2 prior chemotherapy regimens. Results: Twenty-two pts have been enrolled to date, with 11 pts remaining on study and 18 now evaluable. Best responses for the 18 evaluable pts were: 22.2% PR (n=4), 27.8% SD (n=5), and 50% DP (n=9). Eleven pts went off study due to DP (based on CT scan RECIST criteria [n=6] or general deterioration and/or bowel obstruction [n=5]). Median duration on study for the 18 evaluable pts was 15 wks (range 5-63 weeks). Four pts have had PFS >5 months. The 18 evaluable pts received a total of 91 treatment cycles. No pt went off study due to treatment related toxicity or suffered a bowel perforation. Conclusions: Combination bevacizumab and topotecan administered in a weekly fashion demonstrate good activity in platinum refractory OC with acceptable toxicity. G3-G4 Hematologic or Hypertensive Toxicities. [50% disease control (CR+PR+SD) rate among evaluable patients]

Lapatinib (Tykerb™), Carboplatin (Paraplatin®) & Paclitaxel (Taxol™):

  • Phase I/II lapatinib plus carboplatin and paclitaxel in stage III or IV relapsed ovarian cancer patients (2008 ASCO Annual Mtg. Abstr. #5556). The purpose of this study was to establish the MTD and evaluate DLTs and response to therapy of combination therapy with carboplatin/paclitaxel and lapatinib, an oral dual tyrosine kinase inhibitor of both ErbB1 and ErbB2, in Stage III /IV relapsed ovarian cancer. Methods: This was an open-label, multicenter, phase I/II study of carboplatin/paclitaxel in combination with single agent lapatinib in Stage III/IV relapsed ovarian cancer patients. Measurable disease, adequate organ function and ECOG performance status of 0-2 were required. Results: 25 ovarian cancer patients are enrolled and four are too early to be evaluable. The median age is 57 (range 39-81). The median number of prior therapeutic regimens is 4 (range 1-10). GI toxicities were primarily < grade 2 and were successfully treated with aggressive bowel management. 10 patients (pts) experienced G3 toxicities. 4 pts- leukopenia, 2 pts-neutropenia, 2 pts-hyperglycemia, 2 pts-allergic reactions to carboplatin, 1 pt-thrombocytopenia, 1 pt-lymphopenia, 1 pt-hypokalemia, 1 pt-nausea, 1 pt-diarrhea, 1 pt-bowel obstruction. Response to therapy to date is: CR=21%, PR=29%, SD=29%, PD=21%. Two patients who were in complete remission both stopped IV chemotherapy and were maintained only with lapatinib. One is still in remission after six months and one relapsed. Conclusions: Lapatinib, an oral targeted molecular therapy which inhibits both EGFR 1 and 2 tyrosine kinase activity, can be safely administered with a weekly regimen of carboplatin and paclitaxel in heavily pretreated, ovarian cancer patients. The high response rates seen warrant further investigation. [79% disease control (CR+PR+SD) rate among evaluable patients]

Ifomide, Epirubicin, & Cisplatin:

NKTR-102 (Pegylated irinotecan):

  • Phase I dose finding and pharmacokinetic study of NKTR-102 (PEGylated irinotecan): Early evidence of anti-tumor activity (2008 ASCO Annual Mtg. Abstr. #13518 ). NKTR-102 is a novel pegylated form of irinotecan with superior efficacy against a range of xenografts compared with irinotecan. Sustained tumor inhibition is associated with increased SN38 exposure. A phase I trial of NKTR-102 was conducted to establish the MTD and to characterize safety and PK in patients (pts) with refractory solid tumors. No CTC Grade 4 toxicity was observed. G3 diarrhea was dose limiting. Other toxicities included transient uncomplicated G3 neutropenia and transient infusion related visual disturbance. PK data are available for 12 pts. Two partial responses were observed in pts with advanced cervical cancer and small cell lung cancer. Anti-tumor activity was seen in 4 other pts; ovarian: CA-125 decreased from 2557 to 518, Hodgkin’s disease: 28% radiologic improvement with symptomatic benefit, adrenocortical: cortisol levels normalized, metabolic response by PET, esophageal: CEA decreased from 35.5 to 13.6, metabolic response by PET. Conclusions: NKTR-102 shows early evidence of activity in a wide spectrum of tumors. Cumulative SN38 exposure is 1.2 to 6.5 fold higher than that predicted for irinotecan. Toxicity is manageable; diarrhea (not neutropenia) is dose limiting.

ON 01910.Na:

  • Phase I study of ON 01910.Na, a novel polo-like kinase 1 pathway modulator, administered as a weekly 24-hour continuous infusion in patients with advanced cancer (2008 ASCO Annual Mtg. Abstr. #2515). ON 01910.Na induces G2/M cell cycle arrest, apoptosis, and cell death in a broad spectrum of cancer cells, but not in non-neoplastic cells. In vitro, cell killing is dependent on drug exposure time. Based on these preclinical findings, a weekly 24hr continuous infusion (CI) study to determine safety and MTD of ON 01910.Na was initiated. Methods: Patients with advanced cancers received ON 01910.Na as a weekly 24hr CI. Twenty-three pts (7:16 M:F, 45-80 yrs) have received ON 01910.Na. G2 toxicities (2-grade increase over baseline) included fatigue (3 pts) and anorexia (1 pt). Fatigue (11/23 pts) was the most common side effect, with no G3 or greater fatigue observed. Overall, three G3 events occurred, none of which were drug-related. The best response was a pt with advanced ovarian cancer who maintained stable disease for 36 wks of treatment. Conclusions: ON 01910.Na is well tolerated as a weekly 24h continuous infusion. In the dose range studied, the drug exhibited non-linear kinetics with rapid attainment of plasma concentrations that are cytotoxic to cancer cells in vitro, but have limited end-organ toxicity in vivo. Study data continues to accrue, and we expect to recommend a phase II dose shortly. Further analysis and combination phase I studies are planned.

BAY 73-4506:

  • Phase I study of BAY 73-4506, an inhibitor of oncogenic and angiogenic kinases, in patients with advanced solid tumors: Final results of a dose-escalation study (2008 ASCO Annual Mtg. Abstr. #2558 ). BAY 73-4506 is a potent tyrosine kinase inhibitor of receptor tyrosine kinases (VEGFR, PDGF, RET, KIT, FGFR) and serine/threonine kinases (raf and p38MAPK). In tumor xenograft models, BAY 73-4506 demonstrated a broad spectrum antitumor activity. Methods: This phase I study was a dose-escalation trial investigating the safety, PK, and pharmacodynamic (PD) profile of BAY 73-4506, given orally in 21 days on/7 days off cycles, until discontinuation due to toxicity or tumor progression. PK was assessed on days 1 and 21 of cycle 1. PD markers including DCE-MRI, soluble VEGFR-2 (sVEGFR-2) and VEGF plasma levels were assessed at each cycle. Tumor response was evaluated as per RECIST. Results: 52 patients (pts) with solid tumors and progressive disease were enrolled and treated with doses of 10 to 220 mg once daily. Frequent tumor types included colorectal cancer (CRC) (31%), malignant melanoma (10%), and ovarian cancer (10%). The median treatment duration was 49.5 days (min. 3, max. 609). Drug-related adverse events (AEs) of all grades reported in >20% of pts were hoarseness (54%), dermatological toxicities (50%; CTC G3-G4: 13%), mucositis (35%), diarrhea (25%; CTC 3: 2%), fatigue (23%; CTC 3: 2%), and hypertension (23%; CTC 3: 6%). Treatment-related AEs leading to dose reduction, interruption or discontinuation were hand foot skin reaction (15%), diarrhea (8%), and thrombopenia (6%). Of the 33 evaluable pts, 9% achieved a partial response (PR), 64% had stable disease (SD), at least 7 weeks after start of treatment, and 48% had SD or PR for more than 11 weeks. Conclusions: The recommended phase II dose for BAY 73-4506 is 160 mg daily, using the 21 days on/7 days off treatment schedule. Clinical activity (PR+SD) has been demonstrated in 73% of the evaluable pts. An extension cohort (dose level 160 mg) has been started.

Let the Sunshine In!

“People with a vitamin D deficiency are as much as twice as likely to die compared to people whose blood contains higher amounts of the so-called sunshine vitamin, Austrian researchers said on Monday. Their study — the latest to suggest a health benefit from the vitamin — showed death rates from any cause as well as from heart-related problems varied greatly depending on vitamin D. ‘This is the first association study that shows vitamin D affects mortality regardless of the reason for death,’ said Harald Dobnig, an internist and endocrinologist at the University of Graz in Austria who led the study. …Many doctors agree that people with low levels of vitamin D cannot make up for it safely by sitting in the sun, but should take supplements. ‘These results should prompt us to perform vitamin D measurements on a more frequent basis especially in populations at risk,’ Dobnig said.”

“People with a vitamin D deficiency are as much as twice as likely to die compared to people whose blood contains higher amounts of the so-called sunshine vitamin, Austrian researchers said on Monday. Their study — the latest to suggest a health benefit from the vitamin — showed death rates from any cause as well as from heart-related problems varied greatly depending on vitamin D. ‘This is the first association study that shows vitamin D affects mortality regardless of the reason for death,’ said Harald Dobnig, an internist and endocrinologist at the University of Graz in Austria who led the study.

The body makes vitamin D when the skin is exposed to sunlight, a reason for its nickname as the ‘sunshine vitamin.’ It is added to milk and fatty fish like salmon but many people do not get enough of it. Vitamin D helps the body absorb calcium and is considered important for bone health. In adults, vitamin D deficiency can lead to osteoporosis, and it can lead to rickets in children. A number of recent studies have also indicated vitamin D may offer a variety of other health benefits, including protecting against cancer, peripheral artery disease and tuberculosis. Last week, U.S. researchers said vitamin D may extend the lives of people with colon and rectal cancer.

Dobnig and colleagues, who reported their findings in the Archives of Internal Medicine, studied more than 3,200 people with an average age of 62 who were scheduled for a heart exam between 1997 and 2000. During an eight-year follow-up the researchers found that the quarter of volunteers with the lowest levels of vitamin D in their blood were at greater risk of dying. ‘Even when accounting for factors such as heart disease, exercise and other conditions, the researchers found that the risk was double for people with between 5 to 10 nanograms per millilitre of vitamin D in their blood,’ Dobnig said. ‘Most doctors believe people should have between 20 to 30 nanograms per millilitre of the vitamin in their blood,’ he added in a telephone interview.

What causes this effect is not clear, but Dobnig pointed to a host of studies suggesting links to high blood pressure, cancer and fractures as places to begin looking. ‘The potential health risk of low levels of vitamin D should also prod physicians to be more aware of the potential problem, especially for the immobile, elderly and others who spend a great amount of time indoors,’ he added. Many doctors agree that people with low levels of vitamin D cannot make up for it safely by sitting in the sun, but should take supplements. ‘These results should prompt us to perform vitamin D measurements on a more frequent basis especially in populations at risk,’ Dobnig said.”

[Quoted Source: Study shows more benefits of sunshine vitamin, by Michael Kahn, Reuters Health On-Line News Release, June 24, 2008 (summarizing the findings of Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality; Dobnig, H. et. al., Arch Intern Med. 2008 Jun 23;168(12):1340-9.)]

Additional Information:

Updates:

Vermillion Files FDA Pre-Market Application for OVA1 Ovarian Tumor Triage Test

” …The OVA1 [Ovarian Tumor Triage Test] test will help assess the risk of malignancy in the hundreds of thousands of women who require surgery for ovarian tumors each year. ‘This information can be used to identify those who might benefit from referral to a gynecologic oncologist,’ said Fred Ueland, M.D., principal investigator of the study and Associate Professor of Gynecologic Oncology at the University of Kentucky. While most tumors are benign, numerous studies have shown that women with ovarian cancer have better overall outcomes when their surgery is performed by a gynecologic oncologist.”

FREMONT, Calif., June 25 /PRNewswire-FirstCall/ — Vermillion, Inc. (Nasdaq: VRML), a molecular diagnostics company, today announced that it has submitted a 510(k) pre-market notification application to the U.S. Food & Drug Administration (FDA) requesting regulatory clearance of its Ovarian Tumor Triage Test known as OVA1™.

As announced previously, the OVA1 prospective clinical trial met its primary endpoints, indicating that the test is capable of stratifying women with pelvic masses into high- and low-risk categories to help determine whether the patient should be referred to a specialist prior to surgery. The clinical trial was one of the largest ovarian cancer studies ever conducted and assessed more than 550 women with a confirmed adnexal mass at 27 clinical sites in the United States. Additionally, the trial was the culmination of more than eight independent studies in more than 2,500 women.

The OVA1 test will help assess the risk of malignancy in the hundreds of thousands of women who require surgery for ovarian tumors each year. ‘This information can be used to identify those who might benefit from referral to a gynecologic oncologist,’ said Fred Ueland, M.D., principal investigator of the study and Associate Professor of Gynecologic Oncology at the University of Kentucky. While most tumors are benign, numerous studies have shown that women with ovarian cancer have better overall outcomes when their surgery is performed by a gynecologic oncologist.

This is an important milestone for Vermillion and a significant step toward the commercialization of OVA1™. ‘We are pleased with the results of the trial and look forward to discussing the significance of our data and our commercialization strategy in an upcoming investor roundtable, planned for July,’ said Gail Page, President and CEO of Vermillion. ‘We also look forward to receiving regulatory clearance from the FDA and making OVA1 available to the hundreds of thousands of women who could benefit considerably from the test.’

Vermillion will host a roundtable teleconference to address the need for OVA1 on Tuesday, July 15. Fred Ueland, M.D., principal investigator of the OVA1 clinical study, will serve as the keynote speaker. Conference call details, including dial-in information and timing, are forthcoming.

About Vermillion’s Ovarian Cancer Diagnostic Program

In addition to developing a diagnostic test designed to distinguish between benign and malignant pelvic masses, Vermillion has a broad program of ovarian cancer diagnostic tests in development. Studies are underway to validate diagnostic tests developed to detect early-stage ovarian cancer, predict prognosis and recurrence, and identify women considered at high-risk for the disease.

Vermillion’s comprehensive diagnostic development program is being conducted with several leading collaborators at The Johns Hopkins School of Medicine, The University of Texas M.D. Anderson Cancer Center, Rigshospitalet (Copenhagen), and the University of Kentucky.

The Company’s OVA1 test is part of a strategic alliance with Quest Diagnostics to jointly develop and commercialize diagnostic tests.

About Vermillion

Vermillion, Inc. is dedicated to the discovery, 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, hematology, cardiology and women’s health. Vermillion is based in Fremont, California. Additional information about Vermillion can be found on the Web at http://www.vermillion.com.”

[Quoted Source: Vermillion Files 510(k) Application With U.S. Food & Drug Administration for OVA1 Ovarian Tumor Triage Test – Significant Milestone Achieved Based on Compelling Clinical Studies, Vermillion, Inc. Press Release, June 25, 2008.]

Additional Information:  To learn more about molecular diagnostics and proteomics, see Understanding Cancer Series: Molecular Diagnostics, National Cancer Institute, September 1, 2006.

“Dose Dense” Administration of Paclitaxel and Carboplatin Increases Progression Free and Overall Survival in Ovarian Cancer Patients – Is There a New Standard of Care?

“A recent Phase III clinical trial reported that dose dense administration of paclitaxel and carboplatin increased progression free survival (PFS) and overall survival (OS) of ovarian cancer patients when compared to the conventional dose administration of those same drugs. The clinical trial results were reported by the Japanese Gynecologic Oncology Group (JGOG) at the 2008 American Society of Clinical Oncology Annual Meeting held in Chicago, Illinois on May 30th through June 3, 2008.

A recent Phase III clinical trial reported that dose dense administration of paclitaxel and carboplatin increased progression free survival (PFS) and overall survival (OS) of ovarian cancer patients when compared to the conventional dose administration of those same drugs. The clinical trial results were reported by the Japanese Gynecologic Oncology Group (JGOG) at the 2008 American Society of Clinical Oncology Annual Meeting held in Chicago, Illinois on May 30th through June 3, 2008.

The administration of paclitaxel (Taxol™) and carboplatin (Paraplatin™) (referred to as “c-TC”) every three weeks is considered the standard of care for the treatment of ovarian cancer. The clinical trial compared the c-TC with dose dense weekly administration with TC (referred to as “dd-TC”) as first-line chemotherapy for stage II-IV epithelial ovarian, fallopian tube or primary peritoneal cancer. The patients in the trial were randomly assigned to receive carboplatin with either (i) paclitaxel at 180 mg/m² on day 1 (conventional) or (ii) paclitaxel at 80 mg/m² on days 1, 8, and 15 (dose dense). The treatments were repeated every 3 weeks for six cycles; in responding patients, three additional cycles were administered. The primary goal of the trial was to determine patient PFS.

Of 637 patients who underwent randomization, 631 were eligible to participate in the trial. After median follow-up of 29 months, the median duration of PFS in the c-TC group and dd-TC group was 17.1 and 27.9 months, respectively, and overall survival at 2 years was 77.7% and 83.6%, respectively. Among 282 patients with measurable disease, the objective response rates were 53.3% and 55.8% in the c-TC and dd- TC groups respectively. Grade 3 and 4 anemia was reported more frequently in the dd-TC group, and other toxicities were similar in both groups. Based on these findings, the trial investigators concluded that the dd-TC improves PFS as compared with c-TC in patients with advanced epithelial ovarian cancer.

[Source: Randomized phase III trial of conventional paclitaxel and carboplatin (c-TC) versus dose dense weekly paclitaxel and carboplatin (dd-TC) in women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer: Japanese Gynecologic Oncology; S. Isonishi et. al., J. Clin. Oncol. 26: 2008 (May 20 suppl; abstr 5506).]

Comment: It is likely that “dose dense” administration of paclitaxel and carboplatin will become the new standard of care. The institution of a new stardard of care may not be officially established until a second clinical trial repeats the results of the JGOG clinical trial. This result is not entirely surprising because “dose dense” administration of chemotherapy is already the standard of care in the treatment of metastatic breast cancer (click here).

Colectomy “Contributes Significantly” to Ovarian Cancer Maximal Surgical Cytoreduction

“ … Bristow et. al. say: ‘Transverse colectomy can contribute significantly to a maximal ovarian cancer cytoreductive surgical effort and carries acceptable morbidity. Resection of a non-contiguous segment of rectosigmoid colon is frequently necessary, and placement of two separate colonic anastomoses is associated with a low risk of anastomotic breakdown.”

Transverse colectomy can make a valuable contribution to maximal surgical cytoreduction attempts for ovarian cancer, with acceptable morbidity, researchers have found. The study involved 39 ovarian cancer patients, of whom 33 underwent primary surgery for stage IIIC or stage IV disease, Robert Bristow (The Kelly Gynecologic Oncology Service, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA) and team report.

A third of the patients had no residual gross disease after surgery, while 59.0 percent of patients were left with residual disease of 0.1-1.0 cm, and 7.7 percent with residual disease of >1 cm. Morbidity was “acceptable,” affecting 25.6 percent of patients, with fistulas occurring in 5.1 percent of patients, and the mortality rate was 2.6 percent.

Overall, 33 patients underwent partial and nine underwent total transverse colectomy. Surgery involved rectosigmoid colectomy in 61.5 percent of cases and two separate colonic anastamoses in 48.7 percent.

Bristow et. al. say: ‘Transverse colectomy can contribute significantly to a maximal ovarian cancer cytoreductive surgical effort and carries acceptable morbidity. Resection of a non-contiguous segment of rectosigmoid colon is frequently necessary, and placement of two separate colonic anastomoses is associated with a low risk of anastomotic breakdown.’”

[Quoted Source: Colectomy “contributes significantly” to ovarian cancer cytoreduction, by Cher Thornhill, MedWire News Release, June 25, 2008 (summarizing the findings of Transverse colectomy in ovarian cancer surgical cytoreduction: operative technique and clinical outcome; Bristow, R.E. et. al, Gynecol Oncol. 2008 Jun;109(3):364-9. Epub 2008 Apr 8.)]

Symptom Screening + CA-125 Blood Test = Better Detection of Early Stage Ovarian Cancer

” …Research has found that when used alone, a simple four-question symptom-screening questionnaire and the CA125 ovarian-cancer blood test each detect about 60 percent of women with early-stage ovarian cancer and 80 percent of those with late-stage disease. This study found that when used together, the questionnaire and blood test may boost early-detection rates to more than 80 percent and late-stage detection rates to more than 95 percent. …”

“Women’s reports of persistent, recent-onset symptoms linked to ovarian cancer – abdominal or pelvic pain, difficulty eating or feeling full quickly and abdominal bloating – when combined with the CA125 blood test may improve the early detection of ovarian cancer by 20 percent, according to new findings by researchers at Fred Hutchinson Cancer Research Center published online today in CANCER.

Research has found that when used alone, a simple four-question symptom-screening questionnaire and the CA125 ovarian-cancer blood test each detect about 60 percent of women with early-stage ovarian cancer and 80 percent of those with late-stage disease. This study found that when used together, the questionnaire and blood test may boost early-detection rates to more than 80 percent and late-stage detection rates to more than 95 percent.

‘Of course, it is the increase in the detection of early-stage disease that is the most exciting,’ said lead author M. Robyn Andersen, Ph.D., an associate member of the Public Health Sciences Division at the Hutchinson Center. Cure rates for those diagnosed when the disease is confined to the ovary are approximately 70 percent to 90 percent. However, more than 70 percent of women with ovarian cancer are diagnosed with advanced-stage disease, when the survival rate is only 20 percent to 30 percent.

‘This research suggests that if a woman has one or more symptoms that are new for her, having begun within the past year, and if the symptoms happen nearly daily or at least 12 times a month, that may well be a signal to go in and discuss those symptoms with her doctor,’ Andersen said. ‘It’s probably not going to be ovarian cancer, just as most breast lumps are not breast cancer, but it’s still a sign that it might be worth checking with her doctor to see if a CA125 blood test and transvaginal ultrasound may be appropriate.’

Assessing the symptoms included in the symptom-screening index may already be done by some doctors based on a consensus statement issued last year by the National Institutes of Health. The researchers hope their symptom index will help doctors know which among their patients who complain of symptoms such as abdominal swelling and pelvic pain might have cancer.

The symptom-screening index, developed in 2006 by paper co-author Barbara A. Goff, M.D., professor and director of Gynecologic Oncology at the University of Washington School of Medicine, is not used proactively in clinical general practice, but Andersen and colleagues are conducting a pilot study to assess the value of using it as a screening tool among normal-risk women as part of their routine medical-history assessment.

For the just-published study, the researchers administered the symptom questionnaire to 75 women about to undergo surgery for pelvic masses who were later diagnosed with ovarian cancer (the case group), and 254 healthy women at high risk for ovarian cancer due to a family history of the disease (the control, or comparison, group). The cases were recruited through Pacific Gynecology Specialists at Swedish Medical Center in Seattle, and the controls were recruited through the Ovarian Cancer Early Detection Study, a joint project of the Hutchinson Center and the Marsha Rivkin Center for Ovarian Cancer Research.

The National Institutes of Health/National Cancer Institute, the Marsha Rivkin Center for Ovarian Cancer Research and the Canary Foundation supported this research.”

[Quoted Source: Symptom screening plus a simple blood test equals a 20 percent jump in early detection of ovarian cancer, Fred Hutchinson Cancer Research Center News Release, June 23, 2008.]

Webcast: Recognizing and Overcoming Challenges in the Treatment of Recurrent Ovarian Cancer

Maurie Markman, M.D. is the Vice President for Clinical Research at the University of Texas M.D. Anderson Cancer Center located in Houston, Texas. On June 6, 2008, Dr. Markman moderated an expert panel discussion entitled, “Recognizing and Overcoming Challenges in the Treatment of Recurrent Ovarian Cancer.” The panel discussion was recorded as a Continuing Medical Education (CME) webcast. The two doctors participating in the panel discussion with Dr. Markman are (i) William P. McGuire, MD, the Medical Director of the Harry and Jeanette Weinberg Cancer Institute at the Franklin Square Hospital Center, located in Baltimore, Maryland, and (ii) Robert L. Coleman, MD, professor of gynecological oncology at the University of Texas M. D. Anderson Cancer Center.

The expert panel discussion was divided into the two sessions listed below. Click here if you are interested in watching the webcast version of each session. A transcript of each session is also provided below.