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document
Dofequidar fumarate ( MS-209 ) in combination with cyclophosphamide , doxorubicin , and fluorouracil for patients with advanced or recurrent breast cancer . PURPOSE To evaluate the efficacy and tolerability of dofequidar plus cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) therapy in comparison with CAF alone , in patients with advanced or recurrent breast cancer . Dofequidar is a novel , orally active quinoline derivative that reverses multidrug resistance . PATIENTS AND METHODS In this randomized , double-blind , placebo-controlled trial , patients were treated with six cycles of CAF therapy : 28 days/cycle , with doxorubicin ( 25 mg/m2 ) and fluorouracil ( 500 mg/m2 ) administered on days 1 and 8 and cyclophosphamide ( 100 mg orally [ PO ] ) administered on day 1 through 14 . Patients received dofequidar ( 900 mg PO ) 30 minutes before each dose of doxorubicin . Primary end point was overall response rate ( ORR ; partial or complete response ) . In total , 221 patients were assessable . RESULTS ORR was 42.6 % for CAF compared with 53.1 % for dofequidar + CAF , a 24.6 % relative improvement and 10.5 % absolute increase ( P = .077 ) . There was a trend for prolonged progression-free survival ( PFS ; median 241 days for CAF v 366 days for dofequidar + CAF ; P = .145 ) . In retrospectively defined subgroups , significant improvement in PFS in favor of dofequidar was observed in patients who were premenopausal , had no prior therapy , and were stage IV at diagnosis with an intact primary tumor . Except for neutropenia and leukopenia , there was no statistically significant excess of grade 3/4 adverse events compared with CAF . Treatment with dofequidar did not affect the plasma concentration of doxorubicin . CONCLUSION Dofequidar + CAF was well tolerated and is suggested to have efficacy in patients who had not received prior therapy .
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Intervention_Pharmacological
Dofequidar fumarate
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Intervention_Pharmacological
cyclophosphamide , doxorubicin , and fluorouracil
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Intervention_Pharmacological
dofequidar plus cyclophosphamide , doxorubicin , and fluorouracil ( CAF ) therapy
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Intervention_Pharmacological
CAF alone
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
CAF
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Intervention_Pharmacological
doxorubicin
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Intervention_Pharmacological
fluorouracil
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Intervention_Pharmacological
cyclophosphamide
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Intervention_Pharmacological
dofequidar ( 900 mg PO )
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Intervention_Pharmacological
doxorubicin
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Intervention_Pharmacological
CAF
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Intervention_Pharmacological
dofequidar + CAF
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Intervention_Pharmacological
dofequidar
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Intervention_Pharmacological
Dofequidar + CAF
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Outcome_Other
efficacy and tolerability
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Outcome_Physical
overall response rate ( ORR ; partial or complete response ) .
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Outcome_Physical
ORR
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Outcome_Adverse-effects
prolonged progression-free survival ( PFS ;
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Outcome_Mortality
PFS
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Outcome_Physical
neutropenia and leukopenia
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Outcome_Physical
plasma concentration of doxorubicin .
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Participant_Condition
advanced or recurrent breast cancer
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Participant_Condition
advanced or recurrent breast cancer
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Participant_Sample-size
221
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Participant_Condition
premenopausal
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Participant_Condition
no prior therapy
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Participant_Condition
intact primary tumor
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Participant_Condition
not received prior therapy