Ovarian Epithelial Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage III and Stage IV Ovarian Epithelial Cancer Treatment
Notwithstanding these problems, IP therapy for patients with optimally debulked ovarian cancer is receiving wider adoption, and efforts are under way by the GOG to examine some modifications of the IP regimen used in GOG-0172 to improve its tolerability (e.g., to reduce by ≥25% the total 3-hour amount of cisplatin given; a shift from the less practical 24-hour IV administration of paclitaxel to a 3-hour IV administration). A Cochrane-sponsored meta-analysis of all randomized IP versus IV trials shows an HR of 0.79 for disease-free survival and 0.79 for OS, favoring the IP arms. In another meta-analysis of seven IP versus IV randomized trials that were conducted by Cancer Care of Ontario, the relative ratio (RR) of progression at 5 years based on the three trials that reported this endpoint was 0.91 (95% CI, 0.85–0.98) and the RR of death at 5 years based on six trials was 0.88 (95% CI, 0.81–0.95).
Treatment Options for Patients With Suboptimally Cytoreduced Stage III and Stage IV Disease
The value of interval cytoreductive surgery has been the subject of two large phase III trials. In the first study, performed by the EORTC, patients subjected to debulking after four cycles of cyclophosphamide and cisplatin (with additional cycles given later) had an improved survival rate compared with patients who completed six cycles of this chemotherapy without surgery.[Level of evidence: 1iiB] The GOG-0162 trial was designed to answer a very similar question but used the then-standard paclitaxel-plus-cisplatin regimen as the chemotherapy. This trial did not demonstrate any advantage from the use of interval cytoreductive surgery. The divergence of results may be caused by the efficacy of the chemotherapy obscuring any effects of interval cytoreduction, the wider use of maximal surgical effort at the time of diagnosis by U.S. gynecologic oncologists, or unknown factors. Although many patients with stage IV disease also undergo cytoreductive surgery at diagnosis, whether this improves survival has not been established.
First-line treatment of ovarian cancer is cisplatin, given IV, or its second-generation analog, carboplatin, given either alone or in combination with other drugs. Clinical response rates from these drugs regularly exceed 60%, and median time-to-recurrence usually exceeds 1 year in this subset of suboptimally debulked women. Trials by various cooperative groups in the subsequent 2 decades addressed issues of optimal dose-intensity [14,15,16] for both cisplatin and carboplatin, schedule, and the equivalent results obtained with either of these platinum drugs, usually in combination with cyclophosphamide. With the introduction of the taxane paclitaxel, two trials confirmed the superiority of cisplatin combined with paclitaxel to the previous standard of cisplatin plus cyclophosphamide; however, two trials that compared the agent with either cisplatin or carboplatin as a single agent failed to confirm such superiority in all outcome parameters (i.e., response, time-to-progression, and survival) (see Table 2).