Topotecan in patients with advanced neuroendocrine tumors - A phase II study with significant hematologic toxicity

New agents with antitumor activity in neuroendocrine tumors are sorely needed. We therefore conducted a phase II study of topotecan (TOPA) 1.5 mg/m(2)/d for 5 days every 3 weeks in 22 patients with advanced carcinoid and islet cell tumors. Severe neutropenia in 8 of 11 patients (72%) prompted a 30% dose reduction of TOPA to 1.05 mg/m(2) for the final 11 patients enrolled. No objective responses were observed. Eighteen patients have progressed and 14 have died. The median time to progression was 4.2 months (95% CI: 2.9-6.5) and the median survival was 1.9 years (95% CI: 0.63-2.3). Hematologic adverse events were significant, with 16 of 22 patients developing grade IV neutropenia; however, there were no septic deaths. Nonhematologic adverse events were infrequent and were not dose limiting. In conclusion, further studies of this schedule of TOPA in this patient population are not recommended due to the lack of tumor response and significant hematologic toxicity.