Epirubicin (Ellence®) produced longer median overall survival (OS) than ifosfamide (Ifex®) in a recent phase II randomized clinical trial comparing (i) cisplatin, paclitaxel and ifosfamide, with (ii) cisplatin, paclitaxel and epirubicin, in newly diagnosed advanced epithelial ovarian cancer patients. In this trial, patients with histologically proven epithelial ovarian cancer were randomly assigned to receive first-line polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP arm) or cisplatin/paclitaxel/ifosfamide (CIP arm) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms. The Phase II clinical trial finds were as follows:
- Toxicity was predominantly haematological with both regimens; however, anaemia, leucopaenia, neutropaenic fever and use of granulocyte colony-stimulating factors and transfusion were significantly more frequent in the CIP treatment arm;
- Response rates were 85% in the CIP arm and 90% in the CEP arm;
- Complete response rates were 48% in the CIP arm, and 52% in the CEP arm;
- After a median follow-up of 82 months, median overall survival (OS) was 51 months in the CIP arm, and 65 months in the CEP arm; and
- 5-year survival rates were 43% in the CIP arm, and 50% in the CEP arm.
The trial investigators note that the OS findings seem longer in duration than is commonly reported, especially considering that more than 50% of the newly diagnosed advanced ovarian cancer patients were suboptimally debulked or cytoreduced after their first surgery. The trial investigators concluded that this unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach.
[Source: “A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis;” Fruscio R. et. al.; Br J Cancer. 2008 Feb 26;98(4):720-7.]
Comment: Although small in size, this Phase II randomized clinical trial suggests that aggressive surgical intervention followed by aggressive polychemotherapy (involving epirubicin or ifosfamide in tandem with paclitaxel and cisplatin) may increase overall survival in newly diagnosed, advanced-stage ovarian cancer survivors. The findings of at least one major clinical study cite that optimal cytoreduction, as a stand-alone independent factor, provides up to a 50% increase in actuarial survival. In the U.S., an “optimal” cytoreduction is generally defined as a surgical procedure that results in 1 centimeter or less of macroscopic cancer present within the body after surgery. The surprising results of the study discussed above seem to indicate that a suboptimal cytoreduction or debulking surgery followed by aggressive polychemotherapy may be beneficial in extending overall survival in newly diagnosed, advanced-stage ovarian cancer survivors. The issue of what measure should be used to define an “optimal” cytoreduction or debulking is not without controversy with the ovarian cancer arena.