Table 3. Regimens Used in First Relapse continued...
Carboplatin was approved in 1987 for the treatment of patients with ovarian cancer whose disease recurred after treatment with cisplatin, based on improved survival with etoposide or 5-fluorouracil. In a randomized, phase II trial of paclitaxel, a currently used second-line drug, the cisplatin-containing combination of cisplatin plus doxorubicin plus cyclophosphamide (CAP) yielded a superior survival outcome. This, and subsequent studies (see Table 3), have reinforced using carboplatin as the treatment core for patients with platinum-sensitive recurrences. Cisplatin is occasionally used, particularly in combination with other drugs, because of its lesser myelosuppression, but this advantage over carboplatin is counterbalanced by its greater intolerance. Oxaliplatin, initially introduced with the hope that it would overcome platinum resistance, has activity mostly in platinum-sensitive patients  but has not been compared with carboplatin alone or in combinations.
With all platinums, outcome is generally better the longer the initial interval without recurrence from the initial platinum-containing regimens. Therefore, on occasion, patients with platinum-sensitive recurrences relapsing within 1 year have been included in trials of nonplatinum drugs. In one such trial, comparing the pegylated liposomal doxorubicin (PLD) to topotecan, the subset of patients who were platinum sensitive had better outcomes with either drug (and in particular with PLD) relative to the platinum-resistant cohort.
Several randomized trials have addressed whether the use of a platinum in combination with other chemotherapy agents is superior to single agents (see Table 3). In an analysis of data examining jointly the results of three trials performed by the Medical Research Council/Arbeitsgemeinschaft Gynaekologische Onkologie (MRC/AGO) and ICON investigators (known as ICON-4), a platinum-plus-paclitaxel combination yielded a superior outcome, in terms of response rates, progression-free survival (PFS), and overall survival (OS), compared with carboplatin as a single agent or other platinum-containing combinations as controls. Platinum plus paclitaxel was compared with several control regimens, although 71% used carboplatin as a single agent in the control, and 80% used carboplatin plus paclitaxel. Prolonged PFS (HR, 0.76; 95% CI, 0.66-0.89; P = .004) and OS (HR, 0.82; 95% CI, 0.69-0.97; P = .023) were improved in the platinum-plus-paclitaxel arm.; [Level of evidence: 1iiA] The AGO had previously compared the combination of epirubicin plus carboplatin to carboplatin alone and had not found significant differences in outcome.