title: Pooled efficacy analysis from a phase I-II study of biweekly irinotecan in combination with gemcitabine, 5-fluorouracil, leucovorin and cisplatin in patients with metastatic pancreatic cancer.
abstract: Development of treatments to improve the outcomes achieved with single-agent gemcitabine therapy for metastatic pancreatic cancer remains a research priority. G-FLIP (gemcitabine, 5-fluorouracil, leucovorin and cisplatin) is a four-drug regimen designed to maximize sequence-dependent synergy, while attempting to minimize toxicity among the four drugs. The dose-limiting toxicities and maximum tolerated dose of irinotecan as part of the G-FLIP regimen have been published. For phase II testing, G-FLIP consisted of sequential gemcitabine 500 mg/m2 at a fixed rate of 10 mg/m2/min, irinotecan 120 mg/m2, bolus 5-fluorouracil 400 mg/m2 and leucovorin 300 mg, followed by a 24-h 5-fluorouracil infusion of 1500 mg/m2 on day 1 and cisplatin 35 mg/m2 on day 2. Cycles were repeated every 14 days. Thirty-three patients with metastatic pancreatic cancer (22 men and 11 women) were treated and 31 were evaluable. Median patient age was 63 years (range 44-78 years) and median Karnofsky performance status score was 70-80. Estimated median time to disease progression was 171 days (6.1 months) and Kaplan-Meir-estimated median overall survival was 229 days (8.1 months). Twelve- and 18-month survivals were 33 and 21%, respectively. As per Response Evaluation Criteria in Solid Tumors criteria, 13 patients had stable disease, seven (22%) attained a partial response, and 10 (32%) had disease progression. One patient attained a complete response and two were not evaluable (one withdrew consent and one died suddenly, each after cycle 1). Treatment generally was well tolerated. Grade 3-4 toxicities/patient were thrombocytopenia (3.1%), leukopenia (15%), neutropenia (21%), neutropenic fever (3%), fatigue (18%) and thrombosis (12.5%). Common grade 1-2 toxicities per patient included nausea/vomiting (69%), diarrhea (45%), constipation (21%) and fatigue (39%). In conclusion, G-FLIP is a feasible outpatient regimen with acceptable toxicity for metastatic pancreatic cancer patients. Disease control rate (stable disease rate plus partial or complete responses) and 1-year survival outcomes are encouraging.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, St Luke's-Roosevelt Hospital Center, New York, NY, USA.
authors.forename: Anupama
authors.initials: A
authors.lastname: Goel
authors.forename: Michael L
authors.initials: ML
authors.lastname: Grossbard
authors.forename: Stephen
authors.initials: S
authors.lastname: Malamud
authors.forename: Peter
authors.initials: P
authors.lastname: Homel
authors.forename: Margaret
authors.initials: M
authors.lastname: Dietrich
authors.forename: Teresa
authors.initials: T
authors.lastname: Rodriguez
authors.forename: Takhir
authors.initials: T
authors.lastname: Mirzoyev
authors.forename: Peter
authors.initials: P
authors.lastname: Kozuch
mesh_terms: D000328:Adult; D000368:Aged; D000931:Antidotes / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018395:CA-19-9 Antigen / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D018395:CA-19-9 Antigen; D003841:Deoxycytidine; D000077146:Irinotecan; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin; D000093542:Gemcitabine