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document
Safety and efficacy of irinotecan plus high-dose leucovorin and intravenous bolus 5-fluorouracil for metastatic colorectal cancer : pooled analysis of two consecutive southern Italy cooperative oncology group trials . BACKGROUND A biweekly regimen of irinotecan 200 mg/m2 on day 1 and levo-leucovorin ( LV ) 250 mg/m2 plus 5-fluorouracil ( 5-FU ) 850 mg/m2 via intravenous bolus on day 2 was assessed in 2 consecutive randomized trials in metastatic colorectal cancer ( CRC ) . PATIENTS AND METHODS Individual data of 254 patients were merged , and baseline features potentially affecting overall response rate ( ORR ) , progression-free survival ( PFS ) , overall survival ( OS ) , and occurrence of severe toxicity were analyzed by univariate and multivariate analyses . RESULTS In the pooled series , ORR was 33 % ( 95 % confidence interval [ CI ] , 27 % -39 % ) . Liver-only disease ( 47 % vs. 25 % ; P=0.0012 ) and absence of previous weight loss ( 38 % vs. 20 % ; P=0.0189 ) were significantly associated with a higher ORR on the multivariate analysis . Absence of weight loss ( hazard ratio , 1.40 ; 95 % CI , 1.02-1.93 ; P=0.0377 ) was significantly associated with a longer PFS ( 7.5 months vs. 6 months ) . Median OS was 15.1 months ( 95 % CI , 13.5-16.6 months ) . Primary surgery , good performance status ( PS ) , only one metastatic site , and oxaliplatin-based second-line treatment independently predicted a longer OS . Grade 4 neutropenia was significantly associated with a PS > or=1 , whereas risk of grade > or=3 diarrhea was directly related to age and previous weight loss . CONCLUSION Patients with no weight loss and/or preserved PS and with a limited disease extent appeared to obtain the greatest benefit from our irinotecan/5-FU/LV regimen , with acceptable toxicity . Notably , the regimen was effective and well tolerated by elderly patients . This regimen may represent the rationale for assessing the addition of novel antiangiogenic drugs to the treatment of metastatic CRC .
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Intervention_Pharmacological
irinotecan plus high-dose leucovorin
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Intervention_Pharmacological
5-fluorouracil
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Intervention_Pharmacological
irinotecan
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Intervention_Pharmacological
levo-leucovorin ( LV )
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Intervention_Pharmacological
5-fluorouracil ( 5-FU )
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Intervention_Pharmacological
irinotecan/5-FU/LV
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Outcome_Other
Safety
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Outcome_Other
efficacy
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Outcome_Other
overall response rate ( ORR )
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Outcome_Mortality
progression-free survival ( PFS )
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Outcome_Mortality
overall survival ( OS )
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Outcome_Adverse-effects
occurrence of severe toxicity
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Outcome_Physical
ORR
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Outcome_Mental
weight loss
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Outcome_Mortality
Median OS
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Outcome_Mortality
longer OS
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Outcome_Physical
Grade 4 neutropenia
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Outcome_Physical
diarrhea
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Participant_Condition
metastatic colorectal cancer :
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Participant_Condition
southern Italy cooperative oncology group trials .
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Participant_Condition
metastatic colorectal cancer ( CRC ) .
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Participant_Condition
elderly patients .