Topotecan Topotecan is an active second-line treatment for patients with platinum-sensitive and platinum-resistant disease (277–291). In a study of 139 women receiving topotecan 1.5 mg/m2 daily for 5 days, response rates were 19% and 13% in patients with platinum-sensitive and platinum-resistant disease, respectively (287). The predominant toxicity of topotecan is hematologic, especially neutropenia. With the 5-day dosing schedule, approximately 70% to 80% of patients have severe neutropenia, and 25% have febrile neutropenia with or without infection. In some studies, regimens of 5 days produce better response rates than regimens of shorter duration, but in others, reducing the dose to 1.0 mg/m2 per day for 3 days is associated with similar response rates but lower toxicity (280,290). In a study of 31 patients, one-half of whom were platinum refractory, topotecan 2 mg/m2 per day for 3 days every 21 days had a 32% response rate (285). Continuous infusion topotecan (0.4 mg/m2 per day for 14 to 21 days) had a 27% to 35% objective response rate in platinum-refractory patients (284). Weekly topotecan administered at a dose of 4 mg/m2 per week for 3 weeks with a week off every month produced a response rate similar to the 5-day regimen with considerably less toxicity, and this is the preferred dose schedule in the recurrent setting (290).
Oral topotecan, not available in the United States, results in similar response rates with less hematologic toxicity (286). The intravenous and oral formulations of topotecan were compared in a randomized trial of 266 women as a third-line regimen after an initial platinum-based regimen (291). Compared with intravenous topotecan (1.5 mg/m2 daily for 5 days every 3 weeks), oral topotecan (2.3 mg/m2 per day for 5 days every 3 weeks) produced a similar response rate (13% versus 20%), less severe myelosuppression, and only a slightly shorter median survival (51 versus 58 weeks).
Liposomal Doxorubicin Liposomal doxorubicin (Doxil in the United States and Caelyx in Europe), as noted above, has activity in platinum-and taxane-refractory disease (265–268,295). One of the most important side effects of liposomal doxorubicin is the hand-foot syndrome, also known as palmar-plantar erythrodysesthesia or acral erythema, which occurs in 20% of patients who receive 50 mg/m2 every 4 weeks (266). Most oncologists administer 40 mg/m2 and escalate only if there are no side effects. Liposomal doxorubicin has a low rate of alopecia. In a study of 89 patients with platinum-refractory disease, including 82 paclitaxel-resistant patients, liposomal doxorubicin (50 mg/m2 every 3 weeks) produced a response in 17% (1 complete and 14 partial responses) (268). In another study, an objective response of 26% was reported, although there were no responses in women who progressed during first-line therapy (265).