Table 3. Regimens Used in First Relapse continued...
Another trial by European and Canadian groups compared gemcitabine plus carboplatin to carboplatin. The PFS of 8.6 months with the combination was significantly superior to 5.8 months for the carboplatin alone (HR, 0.72; 95% CI, 0.58–0.90; P = .003). The study was not powered to detect significant differences in OS, and the median survival for both arms was 18 months (HR, 0.96; CI, 0.75–1.23; P = .73).
Carboplatin plus paclitaxel has been considered the standard regimen for platinum-sensitive recurrence in the absence of residual neurological toxic effects. The GOG-0213 trial is comparing this regimen to the experimental arm that adds bevacizumab to carboplatin plus paclitaxel.
In a phase III trial, carboplatin plus PLD (CD) was compared to carboplatin plus paclitaxel (CP) in patients with platinum-sensitive recurrence (>6 months). The primary endpoint was PFS with a median PFS for the CD arm of 11.3 months versus 9.4 months for the CP arm (HR, 0.823; 95% CI, 0.72–0.94; P = .005).[Level of evidence: 1iiDiii] The CP arm was associated with increased severe neutropenia, alopecia, neuropathy, and allergic reaction; the CD arm was associated with increased severe thrombocytopenia, nausea, and hand-foot syndrome. Although OS data have not been reported, given its toxicity profile and noninferiority to the standard regimen, CD is an important option for patients with platinum-sensitive recurrence.
Platinum-Refractory or Platinum-Resistant Recurrence
Clinical recurrences that take place within 6 months of completion of a platinum-containing regimen are considered platinum-refractory or platinum-resistant recurrences. Anthracyclines (particularly when formulated as PLD), taxanes, topotecan, and gemcitabine are used as single agents for these recurrences based on activity and their favorable therapeutic indices relative to agents listed in Table 4. The long list underscores the marginal benefit, if any, generally conveyed by these agents. Patients with platinum-resistant disease should be encouraged to enter clinical trials.
Treatment with paclitaxel historically provided the first agent with consistent activity in patients with platinum-refractory or platinum-resistant recurrences.[14,15,16,17,18] Subsequently, randomized studies have indicated that the use of topotecan achieved results that were comparable to those achieved with paclitaxel. Topotecan was compared with PLD in a randomized trial of 474 patients and demonstrated similar response rates, PFS, and OS at the time of the initial report, which was contributed primarily by the platinum-resistant subsets.