A phase II study of irinotecan and cisplatin for metastatic or unresectable high grade neuroendocrine carcinoma

Abstract

15550 Background: High-grade neuroendocrine carcinoma (HGNEC) are rare but aggressive characterized by high mitotic rate. Metastatic disease is incurable. Systemic treatments for HGNEC have been extrapolated from those for small cell lung carcinoma. Effective regimens for HGNEC alone have not been established. The combination of Irinotecan (I), and Cisplatin (P) was evaluated among patients with metastatic or unresectable HGNEC. Methods: Eligible patients were histologically confirmed HGNEC, previously untreated with unresectable or metastatic, measurable disease, adequate bone marrow, renal function, hepatic function and Zubrod performance status < 2. Patients were treated with IP (I 65mg/m2 IV D1+8 and P 25mg/m2 D1+8, every 21 days cycle). Primary endpoints were objective responses and toxicity profile. Response assessed by RECIST every 3 cycles. Dose modification of both drugs was allowed for grade 3/4 toxicities. Results: 20 patients were enrolled from 2003 until 2007, with 19 were evaluable for response and all were evaluable for toxicities. Patients received median of 5 cycles (2–14). 2 (11%) achieved complete response (CR), and 9 (47%) with partial response (PR), with overall objective response in 11 (58%). 3 (16%) attained stable disease (SD) and 5 (26%) with progressive disease (PD). Overall median time to progression (TTP) is 16 weeks (5–43), and among responders TTP 26 weeks (12 weeks for non-responders, p < 0.001). 25 grade 3 toxicities without any patients experiencing grade 4. Specifically, there were 32% leucopenia, 8% anemia, 20% fatigue, 12% nausea, 8% diarrhea, 8% hyponatremia, 4% hypokemia, 4% myalgia, and 4% dyspnea. Total accrual was expected to be 36, but the study was ended early because of slow accrual. Conclusions: The combination of irinotecan and cisplatin is feasible and a well-tolerated option for patients with advanced HGNEC. Responders specifically show a better time to progression. No significant financial relationships to disclose.