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document
Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer . PURPOSE To determine whether addition of the farnesyltransferase inhibitor tipifarnib ( Zarnestra , R115777 ; Johnson and Johnson Pharmaceutical Research and Development , Beerse , Belgium ) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer . PATIENTS AND METHODS This randomized , double-blind , placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy . Tipifarnib was given at 200 mg bid orally continuously ; gemcitabine was given at 1,000 mg/m ( 2 ) intravenously weekly x 7 for 8 weeks , then weekly x 3 every 4 weeks . The primary end point was overall survival ; secondary end points included 6-month and 1-year survival rates , progression-free survival , response rate , safety , and quality of life . RESULTS Six hundred eighty-eight patients were enrolled . Baseline characteristics were well balanced between the two treatment arms . No statistically significant differences in survival parameters were observed . The median overall survival for the experimental arm was 193 v 182 days for the control arm ( P =.75 ) ; 6-month and 1-year survival rates were 53 % and 27 % v 49 % and 24 % for the control arm , respectively ; median progression-free survival was 112 v 109 days for the control arm . Ten drug-related deaths were reported for the experimental arm and seven for the control arm . Neutropenia and thrombocytopenia grade > or = 3 were observed in 40 % and 15 % in the experimental arm versus 30 % and 12 % in the control arm . Incidences of nonhematologic adverse events were similar in two groups . CONCLUSION The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine .
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Intervention_Pharmacological
gemcitabine
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Intervention_Pharmacological
tipifarnib
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Intervention_Pharmacological
gemcitabine
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Intervention_Control
placebo
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Intervention_Pharmacological
tipifarnib
16767
Intervention_Pharmacological
gemcitabine + tipifarnib
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Intervention_Pharmacological
Tipifarnib was given at 200 mg bid orally continuously ; gemcitabine was given at 1,000 mg/m ( 2 ) intravenously weekly x 7 for 8 weeks , then weekly x 3 every 4 weeks .
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Intervention_Pharmacological
gemcitabine and tipifarnib
16770
Outcome_Mortality
overall survival
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Outcome_Mortality
overall survival
16772
Outcome_Mortality
6-month and 1-year survival rates
16773
Outcome_Mortality
progression-free survival
16774
Outcome_Mortality
response rate
16775
Outcome_Mortality
safety
16776
Outcome_Mortality
quality of life
16777
Outcome_Mortality
survival parameters
16778
Outcome_Mortality
median overall survival
16779
Outcome_Mortality
6-month and 1-year survival rates
16780
Outcome_Mortality
median progression-free survival
16781
Outcome_Mortality
drug-related deaths
16782
Outcome_Adverse-effects
nonhematologic adverse events
16783
Participant_Condition
advanced pancreatic adenocarcinoma
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Participant_Sample-size
Six hundred eighty-eight