Platinum-Sensitive Disease The use of combination platinum plus paclitaxel chemotherapy versus a single-agent platinum was tested in two multinational randomized phase III trials and a randomized phase II study (292,293). In a report of the ICON4 and AGO-OVAR-2.2 (AGO Studiengruppe Ovarialkarzinom) trials, 802 women with platinum-sensitive ovarian cancer, who relapsed after being treatment free for at least 6 to 12 months were randomized to platinum-based chemotherapy (72% carboplatin or cisplatin alone; 17% CAP; 4% carboplatin plus cisplatin; and 3% cisplatin plus doxorubicin)or paclitaxel plus platinum-based chemotherapy (80% paclitaxel plus carboplatin; 10% paclitaxel plus cisplatin; 5% paclitaxel plus both carboplatin and cisplatin; and 4% paclitaxel alone) (292). The AGO-OVAR-2.2 trial did not accrue its planned number of patients. In both trials, a significant proportion of the patients did not receive paclitaxel as part of their initial chemotherapeutic regimen. Combining the trials for analysis, there was a significant survival advantage for the paclitaxel-containing therapy (HR = 0.82) with a median follow-up of 42 months. The absolute 2-year survival advantage was 7% (57% versus 50%), and there was a 5-month improvement in median survival (29 versus 24 months). Progression-free survival was better with the paclitaxel regimen (HR = 0.76); there was a 10% difference in 1-year progression-free survival (50% versus 40%) and a 3-month prolongation in median progression-free survival (13 versus 10 months). The toxicities were comparable, except for a significantly higher incidence of neurologic toxicity and alopecia in the paclitaxel group, while myelosuppression was significantly greater with the non-paclitaxel-containing regimens. These data support the slight advantage of a second-line regimen containing both paclitaxel and a platinum agent compared with platinum-based therapy alone in patients who have not received paclitaxel in their primary chemotherapeutic regimen.
There were two randomized trials comparing carboplatin alone to carboplatin and gemcitabine or liposomal doxorubicin (294,295). There was a higher response rate with the combination therapy and a longer progression-free survival, but the studies were not powered to look at overall survival. In the Gynecologic Oncology Intergroup (GCIG) study comparing carboplatin and gemcitabine with carboplatin alone, the response rate was 47.2% for the combination and 30.9% for carboplatin, with the progression-free survival being 8.6 months and 5.8 months, respectively (294). A large GCIG study (CALYPSO) compared carboplatin and liposomal doxorubicin (CD) with carboplatin and paclitaxel (CP) in 976 patients (296). The progression-free survival for the CD arm was statistically superior to CP arm with a median progression-free survival of 11.3 months versus 9.4 months, respectively. Overall survival data are not yet available. The CD arm was better tolerated with less severe toxicities, and this combination is now widely used (296).