Platinum-Resistant and Refractory Disease Patients with platinum-refractory and resistant ovarian cancer are treated with chemotherapy and may have a number of lines of therapy depending on response and performance status. In platinum-refractory patients (i.e., those progressing on treatment), response rates to second-line chemotherapy are less than 10% and the median survival is short, around 3 to 5 months (260–264). The management of women who are platinum-resistant (i.e., progressing within 6 months of completion of chemotherapy) is difficult and “non-cross-resistant agents” are selected, but there does not appear to be one best treatment. Single-agent therapy is typically used because combination regimens are associated with more toxicity without any apparent additional benefit. High response rates of 48% to 64% were reported with dose-dense weekly carboplatin (AUC4) plus paclitaxel (90 mg/m2), and this deserves more study (297). There are a variety of potentially active drugs: paclitaxel, docetaxel, topotecan, liposomal doxorubicin, gemcitabine, oral etoposide, tamoxifen, and bevacizumab are the most frequently used. Other agents include vinorelbine and newer drugs such as trabectedin.
The results of a study comparing topotecan with liposomal doxorubicin demonstrate the low response rates and poor prognosis among women with platinum-resistant ovarian cancer (265). There were two randomized trials comparing liposomal doxorubicin with either topotecan or paclitaxel. In a study of 237 women who relapsed after receiving one platinum-containing regimen, 117 of whom (49.4%) had platinum-refractory disease, liposomal doxorubicin 50 mg/m2 over 1 hour every 4 weeks was compared with topotecan 1.5 mg/m2/day for 5 days every 3 weeks (265). The two treatments had a similar overall response rate (20% versus 17%), time to progression (22 versus 20 weeks), and median overall survival (66 versus 56 weeks). The myelotoxicity was significantly lower in the liposomal doxorubicin-treated patients than with those receiving topotecan. In a second study comparing liposomal doxorubicin with single-agent paclitaxel in 214 platinum-treated patients who had not received prior taxanes, the overall response rates for liposomal doxorubicin and paclitaxel were 18% versus 22%, respectively, and median survival durations were 46 and 56 weeks, respectively, and these were not significantly different (266). In practice, most patients are treated with a starting dose of 40 mg/m2 of liposomal doxorubicin every 4 weeks, because of the toxicity associated with the higher dose and the need to dose reduce when 50 mg/m2 is used. In a subset analysis of platinum-resistant patients, the median time to progression ranged from 9.1 to 13.6 weeks for topotecan and liposomal doxorubicin, respectively. The median survival (p = 0.455) was 35.6 weeks for pegylated liposomal doxorubicin and 41.3 weeks for topotecan. Objective response rates were recorded in 6.5% of patients who received topotecan and in 12.3% of those who received pegylated liposomal doxorubicin (p = 0.118). It is not known whether the treatment improved symptoms control or quality of life because this was not specifically addressed.