title: Randomised phase II study of standard versus chronomodulated CPT-11 plus chronomodulated 5-fluorouracil and folinic acid in advanced colorectal cancer patients.
abstract: In this study, a randomised phase II trial explored the effects of 6-h chronomodulated CPT-11 infusion in advanced colorectal cancer patients. Sixty-eight pre-treated patients were randomly assigned to CPT-11 administered at 180 mg/m2 on day 1, by 1-h infusion (Arm A) or 6-h sinusoidal infusion with peak timing at 5:00 a.m. (Arm B). All patients also received chronomodulated folinic acid/5-fluorouracil (FA/5-FU). Patients in Arm B obtained a 25.7% response rate for 7.0 months duration, a progression-free survival for 8.0 months and a median survival of 28 months. The same data in Arm A were 18.2%, 4.5, 6.0 and 18 months, respectively. No differences in drugs dose-intensity or increased toxicity with prolonged chronomodulated infusion were detected. Major grade 3-4 toxicity was diarrhoea: 10 patients in Arm A and 13 in Arm B. In conclusion, this study has shown that chronomodulated infusion of CPT-11 and FA/5-FU is safe, active and can be integrated with oxaliplatin (EORTC 05011) for the treatment of advanced colorectal cancer.
authors.affiliation: Department of Medical Oncology, Istituto Regina Elena, Via Chianesi, 53, 00144 Rome, Italy. garufi@ifo.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Garufi
authors.forename: Barbara
authors.initials: B
authors.lastname: Vanni
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Aschelter
authors.forename: Albina Rita
authors.initials: AR
authors.lastname: Zappalà
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.forename: Cecila
authors.initials: C
authors.lastname: Nisticò
authors.forename: Isabella
authors.initials: I
authors.lastname: Sperduti
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Edmondo
authors.initials: E
authors.lastname: Terzoli
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D019454:Chronotherapy / Q000009:adverse effects / Q000379:methods*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D002955:Leucovorin; D005472:Fluorouracil