New Treatments for Endometrial Cancer. Part 7
What about chemotherapy? Well the principle drugs we’ve focused on are those that have clearly been shown to be active in concerted phase II trials. The anthracyclines, the taxines and the platinum compounds. Here are the actual numbers for those. Doxorubicin and epirubicin have both shown excellent activity; 27%, 26%. Both platinum compounds, cisplatin and carboplatin, have been shown to be active in about the same range. The response rate in the one trial reported to date with Taxol is actually an excellent 36%. That’s the highest response rate for any single agent in the disease process. The study that has sort of defined what is accepted as the standard of care to this point is a protocol of GOG 107 which randomized patients with advanced or recurrent disease to either Adriamycin alone or a combination of Adriamycin plus cisplatin. Patients were given the regimen every three weeks for a total of eight cycles of treatment. The study had 223 patients on it. The response rate to the combination was 45% compared to 27% with a single agent, highly statistically significant. The complete response rate to the combination was 22% compared to 8% with a single agent, again statistically significant. Median progression free survival with the combination was 6.2 months compared to 3.9 months with the single agent. That difference was also highly statistically significant. There was no difference in overall survival, as you can expect with any overall response rate that is less than 50% in patients with advanced disease. So in terms of response rate, complete response rate and progression free survival, the combination was better. We’ve concluded that the combination ought to be the treatment of choice at the current time.
What is being done in randomized trials in the U.S. – most studies are being done by the GOG – this study has been completed. We are waiting for the data to mature. It compared doxorubicin/cisplatin to a combination of doxorubicin plus Taxol. Then our follow-up study, based on a phase I study that was reported at ASCO in 2006 compares doxorubicin/cisplatin to the three drug combination of doxorubicin/cisplatin/Taxol. This regimen requires GCSF support but those doses are tolerable with GCSF support. And that phase I trial is in abstract form in the proceedings of ASCO 2006. For now, though, the standard of care would have to be considered to be doxorubicin/cisplatin. What we know about chemotherapy; there are five drugs that produce a greater than 20% response rate. Both platinum compounds, two anthracyclines – both doxorubicin and epirubicin – and Taxol. Based on randomized trials doxorubicin/cisplatin is superior to single agents. Doxorubicin/cisplatin is superior to progestins except in receptor positive grade I lesions. Now this is not based on a randomized trial but is based on comparing the data on doxorubicin/cisplatin from the chemotherapy study to data that the GOG has generated on progestins. It’s also important to point out that doxorubicin/cisplatin produces a significant number of complete responses, 22%. The complete responders do have very durable responses that can last a long time.
Endometrial Cancer
To suggest that one ought to give chemotherapy as the first line of systemic therapy is sort of heresy. Chemotherapy yields a superior response rate of 44% versus 21% overall, and superior progression free survival of 6 as compared to 4 months when you put up numbers for the overall population. But if you break the population down by grade, in grade III tumors chemotherapy is clearly superior, 44% response rate versus 12% response rate. In grade I tumors, chemotherapy gives results that are roughly equivalent to progestins, 45 versus 44% response rates and very similar survivals. And that’s despite the fact that the chemotherapy is being given after patients have received prior progestin therapy. The inclusion of Taxol as a front line agent promises improvement. We don’t know that definitively yet but we have reason to believe that that might be the case.
Our recommendations on chemotherapy; doxorubicin/cisplatin is the current treatment of choice. It should be first line systemic therapy for those with grade II or III, or receptor negative tumors. Chemotherapy after failure on hormonal therapy is appropriate and active. The numbers that I’ve shown you for the chemotherapy trials have all been from patients who have received prior progestational therapy. And salvage Taxol is active after doxorubicin/cisplatin according to GOG data.