title: Phase I clinical trial of irinotecan with oral capecitabine in patients with gastrointestinal and other solid malignancies.
abstract: The purpose of this study was to determine the safety of irinotecan and capecitabine in patients with advanced solid tumors. Thirty-four patients received 122 courses of irinotecan 200 to 300 mg/m(2) as an intravenous infusion during 30 minutes on day 1 and capecitabine 1,500 to 3,000 mg/d orally 12 hours apart starting on day 2 for 14 days, repeated every 21 days (one course). Three to seven patients were treated in six dose-escalation cohorts. Three of 7 (43%) patients treated with irinotecan 300 mg/m(2) and capecitabine 2,300 mg/d had course 1 dose-limiting toxicity (DLT) defining maximum tolerated dosage (MTD). Fatigue and diarrhea were the major DLTs, and other events included neutropenia, anorexia, and hand-foot syndrome. At one dose level below the MTD, none of 7 patients treated with irinotecan 275 mg/m(2), and capecitabine 2,300 mg/d (36 courses) had course 1 DLT. Grade III to IV toxicities beyond course 1 included neutropenia (11% of all courses), fatigue (3.4%) and hand-foot syndrome (3.4%). There were only two episodes of febrile grade II neutropenia. There were no toxic deaths. Transient antitumor response was noted in one patient with irinotecan and 5-fluorouracil-refractory colon cancer. The combination of irinotecan 275 mg/m(2) and capecitabine 2,300 mg/d represents a safe, favorable, and convenient outpatient regimen warranting further phase II evaluation.
authors.affiliation: Department of Hematology/Oncology, Montefiore Medical Center/Albert Einstein College of Medicine and Albert Einstein Comprehensive Cancer Center Bronx, NY 10461, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Goel
authors.forename: Minaxi
authors.initials: M
authors.lastname: Jhawer
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rajdev
authors.forename: Una
authors.initials: U
authors.lastname: Hopkins
authors.forename: Karen
authors.initials: K
authors.lastname: Fehn
authors.forename: Cheryl
authors.initials: C
authors.lastname: Baker
authors.forename: Hoo G
authors.initials: HG
authors.lastname: Chun
authors.forename: Della
authors.initials: D
authors.lastname: Makower
authors.forename: Leon
authors.initials: L
authors.lastname: Landau
authors.forename: Anthony
authors.initials: A
authors.lastname: Hoffman
authors.forename: Scott
authors.initials: S
authors.lastname: Wadler
authors.forename: Sridhar
authors.initials: S
authors.lastname: Mani
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin