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/m2/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/m2 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.
Ansell
Stephen M
SM
Divisions of Hematology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
Mahoney
Michelle R
MR
Green
Erin M
EM
Rubin
Joseph
J
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002276:Carcinoid Tumor / Q000188:drug therapy; D018273:Carcinoma, Islet Cell / Q000188:drug therapy; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D019772:Topotecan / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D019772:Topotecan