Superiority of Weekly Paclitaxel Challenges Ovarian Cancer Treatment Paradigm

This just came out February, 2010, and I found it fascinating:

Superiority of Weekly Paclitaxel Challenges Ovarian Cancer Treatment Paradigm

Dr. Maurie Markman is Vice President, Clinical Research; Professor, Gynecologic Medical Oncology; and Chair, Gynecologic Medical Oncology; The University of Texas M.D. Anderson Cancer Center.

1. In your view, which development that has occurred since September 2007 could have the most significant impact on gynecologic oncology?

There were several highly meaningful events over the past year in the management of female pelvic malignancies, but, in my opinion, the single most important report came from the Japanese Gynecologic Oncology Group, as presented at the 2008 Annual Meeting of the American Society of Clinical Oncology (ASCO). These investigators presented preliminary data from their randomized phase III trial that compared a regimen of carboplatin (delivered every 3 weeks) plus paclitaxel, administered either on an every-3-weeks schedule (standard approach) or weekly (experimental approach) (J Clin Oncol. 2008;26:294s).
The study revealed a highly statistically significant 11-month improvement in median progression-free survival in favor of the weekly schedule (17.2 vs 28 months; P = .0015; hazard ratio [HR], 0.714), and a more modest improvement in 2-year overall survival (77% vs 83.6%; P = 0.0496; HR, 0.735). Data on median overall survival were not available at the time of the ASCO presentation.

2. What specific changes in oncology have you observed or do you foresee as a result of this development?

This study seriously challenges the current management paradigm for the use of paclitaxel in ovarian cancer, whereby the agent is routinely employed on an every-3-weeks schedule. These data also raise the issue of whether paclitaxel should be delivered on the more frequent schedule in the treatment of endometrial and cervical cancer, for which paclitaxel is a component of several routinely administered treatment programs.
Future studies in ovarian cancer will need to consider employing the weekly approach. In addition, the implications of the new results for any ongoing studies (including those exploring the addition of novel targeted therapies) that are employing an every-3-weeks regimen, rather than weekly administration, will need to be addressed.
I believe that, based on the data from this important Japanese trial, oncologists should consider the use of weekly paclitaxel with carboplatin as primary therapy for advanced ovarian cancer.

3. Could you put this development into historical perspective for the practicing oncologist?

This was the first evidence-based, randomized, phase III trial reported in more than a decade that has revealed an improvement in outcome for a systemically delivered chemotherapy strategy administered as primary treatment of advanced ovarian cancer. (Three randomized trials over this period have shown the superiority of intraperitoneal cisplatin, compared with the systemic delivery of this agent, when employed as front-line therapy for small-volume residual advanced ovarian cancer.)

While the Japanese Gynecologic Oncology Group trial is only a single study, the results are consistent with those from 2 recently reported studies in breast cancer that demonstrated the superiority of weekly scheduling over an every-3-weeks paclitaxel regimen (N Engl J Med 2008;358:1663-1671; J Clin Oncol 2008;26:1642). These data provide important support for the validity of the Japanese phase III trial.

4. Would you sum up, in a single sentence, why you chose this development as the top story of the past year?

I consider this development to be the single most important event in the management of female pelvic malignancies because it challenges the long-standing (>10-year) existing paradigm in the systemic treatment of ovarian cancer, and it represents an approach that may be employed in several settings to improve outcomes in gynecologic malignancies.