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document
Single-agent irinotecan or FOLFIRI as second-line chemotherapy for advanced colorectal cancer ; results of a randomised phase II study ( DaVINCI ) and meta-analysis [ corrected ] . BACKGROUND Second-line treatment with irinotecan for advanced or metastatic colorectal cancer prolongs survival . It is uncertain whether irinotecan is better administered with 5-fluorouracil or alone in patients previously treated with a fluoropyrimidine . We compared toxicity ( particularly diarrhoea ) , quality of life , and efficacy of combination chemotherapy and irinotecan in these patients . METHODS In DaVINCI , a randomised phase II trial , patients with advanced colorectal cancer were randomly allocated to : Combination therapy ( FOLFIRI ) , irinotecan ( 180 mg/m ( 2 ) IV over 90 min , day 1 ) , 5-fluorouracil ( 400mg/m ( 2 ) IV bolus and 2400 mg/m ( 2 ) by 46-hour infusion from day 1 ) and folinic acid ( 20mg/m ( 2 ) IV bolus , day 1 ) , 2-weekly ; or Single-agent , irinotecan ( 350 mg/m ( 2 ) IV over 90 min ) , 3-weekly . Toxicity was evaluated every treatment cycle ; QOL and response 6-weekly . Analysis was by intention to treat . The trial , amended from a larger factorial design , was terminated early due to slow recruitment . Results were also combined with other second-line irinotecan trials . FINDINGS We randomised 44 patients to combination and 45 to single agent . Eight patients in the irinotecan arm and 4 in the combination arm had grade 3/4 diarrhoea ( P=0.24 ) . Treatment groups did not differ significantly in overall QOL changes , response rate or progression free or overall-survival . In a systematic review of 29 trials of second-line irinotecan-based treatment , single-agent irinotecan was associated with more diarrhoea and alopecia than the combination but efficacy was similar . INTERPRETATION Combination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes . Both regimens remain as reasonable treatment options . FUNDING Research grant ( Pfizer ) .
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Intervention_Pharmacological
irinotecan
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Intervention_Pharmacological
FOLFIRI
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Intervention_Physical
chemotherapy
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Intervention_Pharmacological
irinotecan
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Intervention_Pharmacological
irinotecan
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Intervention_Pharmacological
5-fluorouracil
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Intervention_Pharmacological
fluoropyrimidine
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Intervention_Physical
chemotherapy
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Intervention_Pharmacological
irinotecan
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Intervention_Pharmacological
FOLFIRI
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Intervention_Pharmacological
irinotecan
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Intervention_Pharmacological
5-fluorouracil
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Intervention_Pharmacological
folinic acid
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Intervention_Pharmacological
irinotecan
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Intervention_Pharmacological
irinotecan
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Intervention_Pharmacological
irinotecan-based
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Intervention_Pharmacological
irinotecan
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Intervention_Physical
Combination treatment
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Intervention_Pharmacological
irinotecan
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Outcome_Physical
advanced colorectal cancer
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Outcome_Mortality
survival .
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Outcome_Adverse-effects
Toxicity
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Outcome_Adverse-effects
grade 3/4 diarrhoea
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Outcome_Other
overall QOL changes
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Outcome_Other
response rate
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Outcome_Other
progression free
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Outcome_Mortality
or overall-survival
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Outcome_Adverse-effects
diarrhoea
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Outcome_Adverse-effects
alopecia
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Outcome_Adverse-effects
alopecia and diarrhoea
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Outcome_Other
efficacy on clinical outcomes