In another randomized trial in 195 patients with platinum-resistant ovarian cancer, patients were randomized to receive either liposomal doxorubicin (PLD) or gemcitabine (298). In the gemcitabine and PLD groups, median progression-free survival was 3.6 versus 3.1 months; median overall survival was 12.7 versus 13.5 months; overall response rate was 6.1% versus 8.3%; and in the subset of patients with measurable disease, overall response rate was 9.2% versus 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea or vomiting, fatigue, and neutropenia.
Some researchers attempted to treat patients with non-platinum drugs to prolong the platinum-free interval, hoping that would allow the tumor to become platinum-sensitive during the interval use of non-cross-resistant agents. The rationale for this approach is the belief that the platinum-free interval is equivalent to the treatment-free interval, and before the availability of other active drugs, these two terms were synonymous. There are no data to support the hypothesis that the interposition of another drug can produce an increased platinum sensitivity as a result of a longer interval since the last platinum treatment.
Single-agent paclitaxel shows objective responses in 20% to 30% in phase II trials of women with platinum-resistant ovarian cancer (269–274). The main toxicities are fatigue and peripheral neuropathy. Weekly paclitaxel is active, and the toxicity, especially myelosuppression, is less than with the every 3-week regimens. In a study of 53 women with platinum-resistant ovarian cancer, weekly paclitaxel (80 mg/m2 over 1 hour) had an objective response of 25% in patients with measurable disease, and 27% of patients without measurable disease had a 75% decline in serum CA125 levels (269).
Docetaxel has some activity in these patients (299–301). The GOG studied 60 women with platinum-resistant ovarian or primary peritoneal cancer (301). Although there was a 22% objective response rate, the median response duration was only 2.5 months, and therapy was complicated by severe neutropenia in three-quarters of the patients.