Standard-Dose Intravenous Cisplatin vs. Moderately High-Dose Carboplatin
Standard-Dose Intravenous Cisplatin vs. Moderately High-Dose Carboplatin
Abstract & Commentary
Synopsis: An experimental regimen including moderately high-dose IV carboplatin followed by IP paclitaxel and IV cisplatin yielded a significant improvement in progression-free survival when compared with a standard regimen of IV cisplatin and paclitaxel.
Source: Markman M, et al. J Clin Oncol. 2001;19:
1001-1007.
In a report of an intergroup study involving 3 cooperative groups, Markman and colleagues compared the progression-free and overall survival in small-volume residual ovarian cancer after treatment with intravenous (IV) cisplatin and paclitaxel for 6 cycles, or an experimental regimen of IV moderately high-dose carboplatin for 2 cycles followed by IV paclitaxel and intraperitoneal cisplatin for 6 cycles. Of the 523 patients who entered this trial, 462 were determined to be assessable, with prognostic factors well balanced between the treatments. Neutropenia, thrombocytopenia, and gastrointestinal and metabolic toxicities were greater in the experimental arm. As a result, 18% of the patients received less than 2 courses of IP therapy. Progression-free survival was superior for patients randomized to the experimental treatment arm (median, 28 vs 22 months; relative risk, 0.78; log-rank P = .01). There was a borderline improvement in overall survival associated with this regimen (median, 63 vs 52 months; relative risk, 0.81; P = .05). Markman et al concluded that the experimental regimen including moderately high-dose IV carboplatin followed by IV paclitaxel and intraperitoneal (IP) cisplatin yielded a significant improvement in progression-free survival when compared with a standard regimen of IV cisplatin and paclitaxel. Because the improvement in overall survival was of borderline statistical significance and toxicity was greater, Markman et al did not recommend the experimental arm for routine use.
Comment by David M. Gershenson, MD
After more than 2 decades of study, we still do not know the role of IP chemotherapy in the management of epithelial ovarian cancer. Several phase II clinical trials of IP chemotherapy in patients with recurrent ovarian cancer have demonstrated antitumor activity of a variety of drugs. However, only through direct comparisons with IV chemotherapy can we understand the true benefit of such an approach. We certainly do know that IP chemotherapy is feasible and generally safe. A previous intergroup study comparing IV cyclophosphamide/IP cisplatin with IV cyclophosphamide/IV cisplatin showed a superior overall survival for the IP group (median, 49 vs 41 months).1 However, this study was criticized for several design and analysis flaws. The present study certainly does not answer the question as to whether IP chemotherapy is advantageous as primary therapy for advanced epithelial ovarian cancer. The survival advantage was borderline, and the "IP arm" really was a package that included moderately high-dose IV carboplatin (a design flaw that the investigators recognized at the outset). The current Gynecologic Oncology Group (GOG) randomized trial studying the role of IP cisplatin and paclitaxel with IV paclitaxel should provide a better answer. If that study is negative, that may sound an end to the use of IP chemotherapy for ovarian cancer.
Reference
1. Alberts DS, et al. N Engl J Med. 1996;335:1950-1955.
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