title: Biweekly bolus 5-fluorouracil and leucovorin plus oxaliplatin in pretreated patients with advanced colorectal cancer: a dose-finding study.
abstract: The primary objective of this study was to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) for bolus 5-fluorouracil (5-FU) administered on a biweekly schedule and in combination with fixed doses of leucovorin (LV) and oxaliplatin. The secondary objectives were to evaluate the toxicity profile and antitumor activity of this regimen for pre-treated patients with advanced colorectal cancer. A total of 26 patients with documented fluoropyrimidine-resistant, advanced colorectal cancer were enrolled into this phase I study. Fixed dose of oxaliplatin (85 mg/m2) was delivered as an i.v. infusion over 2 h, followed by LV (20 mg/m2) and 5-FU bolus every 2 weeks. The starting dose of 5-FU was 600 mg/m2, which was then incremented by 100 mg/m2 for each dose level. The DLT was determined for the first two treatment cycles, while toxicity and efficacy were evaluated throughout treatment. Six dose levels were tested. The MTD of 5-FU was deemed to be 1000 mg/m2 since dose-limiting fatigue was noted for three of the five-patient cohort during the first two cycles of chemotherapy at dose level 6. The most frequent treatment-related toxicities during the study were neutropenia, vomiting, diarrhea, fatigue and neuropathy. In an intent-to-treat analysis, the objective response rate was 30.8% (95% confidence interval 11.8-49.8%) for the 26 patients. The combination of bolus 5-FU/LV and oxaliplatin every 2 weeks is a feasible and effective treatment at the recommended dosages. A phase II study, to more-precisely define activity and toxicity, is ongoing.
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan, ROC. tsyangss@ms27.hinet.net
authors.forename: Tsai-Shen
authors.initials: TS
authors.lastname: Yang
authors.forename: Jinn-Shium
authors.initials: JS
authors.lastname: Chen
authors.forename: Reiping
authors.initials: R
authors.lastname: Tang
authors.forename: Jy-Ming
authors.initials: JM
authors.lastname: Chiang
authors.forename: Pau-Shiu
authors.initials: PS
authors.lastname: Hsieh
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Yeh
authors.forename: Chung-Rong
authors.initials: CR
authors.lastname: Changchien
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000627:therapeutic use*; D000077150:Oxaliplatin; D016879:Salvage Therapy; D015996:Survival Rate; D013997:Time Factors
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil