title: A phase II trial of irinotecan and cisplatin in patients with metastatic neuroendocrine tumors.
abstract: The role of systemic chemotherapy in the treatment of patients with metastatic neuroendocrine tumors is controversial. While combination regimens containing cisplatin and etoposide have activity against more aggressive neuroendocrine tumor variants, such regimens appear to have little efficacy in patients with well-differentiated neuroendocrine tumor subtypes. The combination of irinotecan and cisplatin is active both against small cell lung cancer and in upper gastrointestinal malignancies but has not been prospectively evaluated in patients with metastatic neuroendocrine tumors. We therefore assessed the efficacy of an irinotecan/cisplatin combination in patients with this disease. Eighteen patients with metastatic neuroendocrine tumors (excluding small cell carcinoma) were treated with irinotecan, 65 mg/m2, and cisplatin, 30 mg/m2, administered weekly for 2 of every 3 weeks. Patients were followed for evidence of toxicity, response, and survival. The toxicities associated with this regimen were mild and included myelosuppression, nausea, and diarrhea. Only one radiologic response was observed among four patients with poorly differentiated neuroendocrine tumors. No radiologic responses were observed in 14 patients with well-differentiated tumors. The median overall survival duration of patients treated with this regimen was 11.4 months. We conclude that while the combination of irinotecan and cisplatin may have activity in aggressive neuroendocrine tumor subtypes, this combination is inactive in patients with well-differentiated neuroendocrine tumors.
authors.affiliation: Department of Medical Oncology, Dana- Institute, Boston, Massachusetts, USA. matthew_kulke@dfci.harvard.edu
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Kulke
authors.forename: Bingyan
authors.initials: B
authors.lastname: Wu
authors.forename: David P
authors.initials: DP
authors.lastname: Ryan
authors.forename: Peter C
authors.initials: PC
authors.lastname: Enzinger
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Clark
authors.forename: Craig C
authors.initials: CC
authors.lastname: Earle
authors.forename: Ann
authors.initials: A
authors.lastname: Michelini
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002945:Cisplatin / Q000008:administration & dosage*; D004067:Digestive System Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin