title: Optimisation of irinotecan dose in the treatment of patients with metastatic colorectal cancer after 5-FU failure: results from a multinational, randomised phase II study.
abstract: Although irinotecan 350 mg m(-2) is a standard option for relapsed/refractory advanced colorectal cancer, there is some evidence that suggests that a higher dose may be more effective, with acceptable tolerability, following 5-fluorouracil (5-FU). This study assessed the optimal dosing strategy for irinotecan, along with treatment efficacy and safety. A total of 164 patients with metastatic colorectal cancer progressing after failure on 5-FU or raltitrexed received either 350 mg m(-2) irinotecan (Group A; n=36) or 250, 350 or 500 mg m(-2), according to individual patient tolerance (Group B; n=62) or based on risk factor optimisation (Group C; n=66). There were no complete responses. There was a trend towards a higher overall response rate in Group B (13%) than in Groups A (8%) and C (9%). Tumour control growth rate was high in all three groups: 58% in group A, 60% in Group B and 50% in Group C. A total of 34% of patients in Group B and 9% in Group C were able to receive a dose of 500 mg m(-2). Median duration of response and time to progression were significantly longer in Groups A and B compared with Group C. No significant between-group differences for any adverse events were seen, although there was a small trend towards better tolerability in Group B. Individual dose escalation based on patient tolerance may allow more patients to receive a higher irinotecan dose without causing additional toxicity and can be an appropriate patient management strategy.
authors.affiliation: University Hospital Gasthuisberg, 3000 Leuven, Belgium. eric.vancutsem@uz.kuleuven.ac.be
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: L
authors.initials: L
authors.lastname: Dirix
authors.forename: J-L
authors.initials: JL
authors.lastname: Van Laethem
authors.forename: S
authors.initials: S
authors.lastname: Van Belle
authors.forename: M
authors.initials: M
authors.lastname: Borner
authors.forename: M
authors.initials: M
authors.lastname: Gonzalez Baron
authors.forename: A
authors.initials: A
authors.lastname: Roth
authors.forename: R
authors.initials: R
authors.lastname: Morant
authors.forename: E
authors.initials: E
authors.lastname: Joosens
authors.forename: G
authors.initials: G
authors.lastname: Gruia
authors.forename: D
authors.initials: D
authors.lastname: Sibaud
authors.forename: H
authors.initials: H
authors.lastname: Bleiberg
mesh_terms: D000328:Adult; D000368:Aged; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017211:Treatment Failure
chemical_list: D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin