10357
document
Randomized comparative study of tegafur/uracil and oral leucovorin versus parenteral fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer . PURPOSE This phase III study compared the time to progression ( TTP ) of an oral regimen of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine composed of a fixed combination of tegafur and uracil in a 1:4 molar ratio ( UFT ) and leucovorin ( LV ) to intravenous ( IV ) fluorouracil ( 5-FU ) and LV in previously untreated metastatic colorectal carcinoma ( CRC ) patients . Secondary end points were survival , tumor response , safety , and quality of life . PATIENTS AND METHODS Between May 1996 and July 1997 , 380 patients were randomized to receive either UFT ( 300 mg/m ( 2 ) /d ) and LV ( 90 mg/d ) , administered for 28 days every 35 days , or 5-FU ( 425 mg/m ( 2 ) /d ) and LV ( 20 mg/m ( 2 ) /d ) , given IV for 5 days every 35 days . RESULTS No statistically significant difference in TTP was observed between treatments . With 320 events assessed , the median TTP was 3.4 months ( 95 % Confidence interval [ CI ] , 2.6 to 3.8 ) on UFT/LV and 3.3 months ( 95 % CI , 2.5 to 3.7 ) on 5-FU/LV ( P =.591 , stratified log-rank test ) . There were no statistically significant differences in survival , tumor response , duration of response , and time to response . Substantial safety benefits were observed in patients treated with UFT/LV . They experienced significantly less stomatitis/mucositis ( P < .001 ) and myelosuppression , resulting in fewer episodes of febrile neutropenia ( P < .001 ) and less documented infection ( P =.04 ) . Concomitant medication usage was significantly greater on 5-FU/LV ( P =.010 ) . With respect to quality of life , after correcting for baseline imbalances , there were no significant differences between treatments for any scale , except diarrhea . CONCLUSION The oral UFT/LV regimen failed to achieve improved TTP ; however , the study confirms significant safety improvements compared with bolus IV 5-FU/LV for the first-line treatment of metastatic CRC .
10358
Intervention_Pharmacological
tegafur/uracil and oral leucovorin versus parenteral fluorouracil and leucovorin
10359
Intervention_Pharmacological
dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine
10360
Intervention_Pharmacological
tegafur and uracil
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Intervention_Pharmacological
leucovorin
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Intervention_Pharmacological
intravenous ( IV ) fluorouracil
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Intervention_Pharmacological
and LV
10364
Intervention_Pharmacological
UFT
10365
Intervention_Pharmacological
LV
10366
Intervention_Pharmacological
5-FU
10367
Intervention_Pharmacological
LV
10368
Outcome_Other
time to progression ( TTP )
10369
Outcome_Mortality
survival
10370
Outcome_Physical
tumor response
10371
Outcome_Other
safety
10372
Outcome_Physical
quality of life
10373
Outcome_Physical
TTP
10374
Outcome_Other
TTP
10375
Outcome_Mortality
survival
10376
Outcome_Physical
tumor response
10377
Outcome_Physical
duration of response
10378
Outcome_Physical
time to response
10379
Outcome_Other
safety benefits
10380
Outcome_Physical
stomatitis/mucositis
10381
Outcome_Physical
myelosuppression
10382
Outcome_Physical
febrile neutropenia
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Outcome_Physical
documented infection
10384
Outcome_Other
quality of life
10385
Outcome_Adverse-effects
diarrhea
10386
Outcome_Physical
TTP
10387
Participant_Condition
metastatic colorectal cancer
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Participant_Condition
previously untreated metastatic colorectal carcinoma ( CRC ) patients .
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Participant_Sample-size
380 patients