title: Chronotherapy with 5-fluorouracil, folinic acid and carboplatin for metastatic colorectal cancer; an interesting therapeutic index in a phase II trial.
abstract: The aim of this study was to develop a phase II study gauging the contribution of a daily low-dose of carboplatin combined with 5-fluorouracil (5-FU) and folinic acid (FOL) in a chronotherapy schedule for advanced colorectal cancer patients. 60 patients with metastatic colorectal cancer were included in a phase II trial in which 50% of patients had received prior chemotherapy of up to three regimens. Treatment consisted of a combination of 5-FU (700 mg/m(2)/day) and FOL (300 mg/m(2)/day) infused from 10.00 pm to 10. 00 am peaking at 4.00 am with carboplatin infused from 10.00 am to 10.00 pm at 40 mg/m(2)/day with a peak at 4.00 pm. 4-day courses were repeated every 2 weeks in an ambulatory setting with a programmable pump. Patients experienced excellent tolerance (grades III-IV%): diarrhoea, 8.1; nausea/vomiting, 4.8; mucositis, 3.2; skin or neurological 1.7; granulocytes 29.0; platelets and haemoglobin (Hb) 9.7. Major tumour responses were observed in 47% of cases, 4 complete response (CR), 24 partial response (PR); 3 CR and 6 PR (69%) were recorded in 13 previously untreated patients; 11 (18%) underwent subsequent surgical resection of residual metastases. Median survival was 14.6 months with 22% patients surviving over 2 years (35% survival for responders versus 0 for non-responders). In conclusion, this chronotherapy determined administration of 5-FU/FOL and carboplatin yielded an excellent therapeutic index for the combination and warrants further evaluation in the first-line treatment of metastatic colorectal cancer.
authors.affiliation: Department of Medical Oncology, Les Cliniques Saint-Joseph, Rue de Hesbaye 75-4000, Liege, Belgium. christian.focan@lescliniquesstjoseph.be
authors.forename: C
authors.initials: C
authors.lastname: Focan
authors.forename: F
authors.initials: F
authors.lastname: Kreutz
authors.forename: D
authors.initials: D
authors.lastname: Focan-Henrard
authors.forename: N
authors.initials: N
authors.lastname: Moeneclaey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D019454:Chronotherapy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015918:Infusion Pumps, Implantable; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D002955:Leucovorin; D005472:Fluorouracil