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A randomized , double-blind , phase II study of two doses of pemetrexed as first-line chemotherapy for advanced breast cancer . PURPOSE Pemetrexed has shown varied response rates in advanced breast cancer . This randomized , double-blind , phase II study was conducted to assess the efficacy and safety of two doses of pemetrexed in a homogeneous population . A secondary objective was to identify molecular biomarkers correlating with response and toxicity . EXPERIMENTAL DESIGN Patients with newly diagnosed metastatic breast cancer or locally recurrent breast cancer received 600 mg/m ( 2 ) ( P600 arm ) or 900 mg/m ( 2 ) ( P900 arm ) of pemetrexed on day 1 of a 21-day cycle . All patients received folic acid and vitamin B ( 12 ) supplementation . RESULTS The P600 ( 47 patients ) and P900 ( 45 patients ) arms had response rates of 17.0 % ( 95 % confidence interval , 7.7-30.8 % ) and 15.6 % ( 95 % confidence interval , 6.5-29.5 % ) with approximately 50 % stable disease per arm , median progression-free survival of 4.2 and 4.1 months , and median times to tumor progression of 4.2 and 4.6 months , respectively . Both arms exhibited minimal toxicity ( grade 3/4 neutropenia < 20 % , leukopenia < 9 % , and other toxicities < 5 % ) . Tumor samples from 49 patients were assessed for the expression levels of 12 pemetrexed-related genes . Folylpolyglutamate synthetase and thymidine phosphorylase correlated with efficacy . Best response rates and median time to tumor progression for high versus low thymidine phosphorylase expression were 27.6 % versus 6.3 % ( P = 0.023 ) and 5.4 versus 1.9 months ( P = 0.076 ) , and for folylpolyglutamate synthetase were 37.5 % versus 10.0 % ( P = 0.115 ) and 8.6 versus 3.0 months ( P = 0.019 ) , respectively . gamma-Glutamyl hydrolase expression correlated with grade 3/4 toxicities : 78.6 % for high versus 27.3 % for low gamma-glutamyl hydrolase ( P = 0.024 ) . CONCLUSION The two pemetrexed doses yielded similar efficacy and safety profiles . Exploratory biomarker analysis identified efficacy and toxicity correlations and warrants further evaluation .
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Intervention_Pharmacological
pemetrexed
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Intervention_Pharmacological
Pemetrexed
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Intervention_Pharmacological
pemetrexed
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Intervention_Pharmacological
P600
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Intervention_Pharmacological
P900
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Intervention_Pharmacological
pemetrexed
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Intervention_Pharmacological
folic acid
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Intervention_Pharmacological
vitamin B ( 12 )
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Intervention_Pharmacological
pemetrexed-related
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Intervention_Pharmacological
pemetrexed
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Outcome_Other
efficacy
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Outcome_Other
safety
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Outcome_Other
response
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Outcome_Adverse-effects
toxicity
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Outcome_Other
response rates
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Outcome_Mortality
median progression-free survival
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Outcome_Other
median
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Outcome_Physical
times to tumor progression
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Outcome_Adverse-effects
minimal toxicity
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Outcome_Adverse-effects
neutropenia
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Outcome_Adverse-effects
leukopenia
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Outcome_Adverse-effects
other toxicities
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Outcome_Other
efficacy
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Outcome_Other
Best response rates
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Outcome_Other
median
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Outcome_Physical
time to tumor progression
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Outcome_Adverse-effects
grade 3/4 toxicities
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Outcome_Other
efficacy
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Outcome_Other
safety
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Outcome_Other
efficacy
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Outcome_Adverse-effects
toxicity
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Participant_Condition
advanced breast cancer .
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Participant_Condition
advanced breast cancer .
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Participant_Condition
diagnosed metastatic breast cancer
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Participant_Condition
breast cancer
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Participant_Sample-size
47 patients )
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Participant_Sample-size
P900 ( 45 patients