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Phase I randomized, placebo-controlled, cross-over dose-finding pharmacokinetic study of Coenzyme Q10 during one cycle of doxorubicin treatment for breast cancer.
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  • Heather Greenlee,
  • Katherine Crew,
  • Matthew Maurer,
  • Kevin Kalinsky,
  • Serge Cremers,
  • Ali Naini,
  • Wei Yann Tsai,
  • Zaixing Shi,
  • Frances Brogan,
  • Dawn Hershman
Heather Greenlee
Fred Hutchinson Cancer Research Center
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Katherine Crew
Columbia University Mailman School of Public Health
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Matthew Maurer
Bristol-Myers Squibb Co
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Kevin Kalinsky
Herbert Irving Comprehensive Cancer Center
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Serge Cremers
Columbia University
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Ali Naini
Columbia University
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Wei Yann Tsai
Columbia University Mailman School of Public Health
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Zaixing Shi
Columbia University Mailman School of Public Health
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Frances Brogan
Herbert Irving Comprehensive Cancer Center
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Dawn Hershman
Columbia University Mailman School of Public Health
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Abstract

Aim: To determine the safety of Coenzyme Q10 (CoQ10) in breast cancer patients receiving doxorubicin treatment. Methods: Phase I randomized, placebo-controlled, cross-over, dose-finding pharmacokinetic study among women with stage I-III breast cancer receiving 4 cycles of doxorubicin plus cyclophosphamide. The study was designed to test the maximum tolerated dose of CoQ10 using up to 1200 mg/day. Eligible patients were randomized to Arm A (CoQ10 after Cycle 3, followed by placebo after Cycle 4) or Arm B (placebo after cycle 3, followed by CoQ10 after cycle 4). CoQ10 concentrations and total antioxidant capacity (TAC) were measured before and after chemotherapy cycles. Non-compartmental pharmacokinetic parameters of doxorubicin and its active metabolites were measured with and without CoQ10. Paired t-tests assessed intra-patient differences in pharmacokinetic parameters, serum CoQ10 concentrations, TAC and adverse events. Results: Six patients received 300 mg/day of CoQ10 [Arm A (n=3), Arm B (n=3)]. One patient received 600 mg/day of CoQ10 but was discontinued due to non-adherence. Serum CoQ10 concentrations were increased in patients receiving 300 mg/day (mean±SD change: CoQ10, 1.6±0.9 ug/mL; placebo, -0.01±0.3 ug/mL; P=0.01). There were no clinically significant pharmacokinetic interactions between 300 mg/day CoQ10 and doxorubicin and no differences in TAC or adverse events during treatment and nontreatment periods. The trial was closed early due to slow accrual. Conclusions: 300 mg/day of CoQ10 with doxorubicin did not change doxorubicin pharmacokinetics and was not associated with treatment-related adverse events. Future studies should evaluate the long-term effects of CoQ10 at 300 mg/day and safety studies should examine higher doses.