Two randomized, prospective clinical studies compared the combination of paclitaxel and carboplatin to paclitaxel and cisplatin (201,202). In both studies, the efficacy and survivals were similar, but the toxicity was more acceptable with the carboplatin-containing regimen. In the first trial, GOG Protocol 158, the randomization was carboplatin AUC = 7.5 and paclitaxel 175 mg/m2 over 3 hours versus cisplatin 75 mg/m2 and paclitaxel 135 mg/m2 over 24 hours (Fig. 37.15). The disease progression-free survival of the carboplatin-containing arm was 22 months versus 21.7 months for the control arm (201). The gastrointestinal and neurotoxicity of the carboplatin arm were appreciably lower than that of the cisplatin arm. A similar result was obtained in a large randomized trial in Germany, in which the dose of carboplatin was AUC = 6 and paclitaxel was 185 mg/m2 over 3 hours compared with the same dose of paclitaxel and cisplatin 75 mg/m2 (202). Based on these data, the preferred regimen in patients with advanced-stage disease is the paclitaxel plus carboplatin combination (203).
The ICON3 trial was a study of 2,074 women with all stages of ovarian cancer, including 20% who had stage I or II disease (208). Carboplatin plus paclitaxel was compared with two non-paclitaxel regimens, carboplatin (70%), or cyclophosphamide, Adriamycin, and cisplatin (CAP) (30%). The regimens were chosen before randomization and based on the clinical preference of the treating physician. One-third of patients who received carboplatin or CAP subsequently received second-line paclitaxel, and this additional chemotherapy was often given before clinical progression. With a median follow-up of 51 months, the carboplatin plus paclitaxel and the control groups had a similar progression-free survival (0.93) and overall survival (0.98). The median survival for the paclitaxel plus carboplatin and control groups was 36.1 and 35.4 months, respectively. The median duration of progression-free survival was 17.3 and 16.1 months, respectively. The researchers concluded that single agent carboplatin and CAP were as effective as paclitaxel and carboplatin for first-line chemotherapy. Because carboplatin as a single agent had a lower toxicity than the other regimens and the median survival (33 months) was similar in the prior trial (ICON2) that compared carboplatin and CAP as first-line treatment, the researchers suggested that carboplatin alone was the preferred therapy (209).
The design of the study limited the interpretation of the results and was criticized, because patients with FIGO stages I to IV disease were included, the extent of primary surgery was variable, and the majority (85%) of patients who relapsed after single-agent carboplatin or CAP received paclitaxel. The results of this study did not change the practice in the United Kingdom where the study was predominantly carried out.