Phase I Randomized, Placebo-Controlled, Cross-Over Dose-Finding Study of Coenzyme Q10 on Doxorubicin Pharmacokinetics during Breast Cancer Treatment

Aim: To determine effects of Coenzyme Q10 (CoQ10) supplementation in breast cancer patients receiving doxorubicin treatment. Methods: Phase I randomized, placebo-controlled, cross-over, dose-finding study among women with stage I-III breast cancer receiving 4 cycles of doxorubicin plus cyclophosphamide. The study was designed to test effects on doxorubicin pharmacokinetic parameters when administering up to the maximum tolerated dose of CoQ10 of 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 µg/mL; placebo, −0.01 ± 0.3 µg/mL; P = .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. Conclusion: 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. Trial registration: ClinicalTrials.gov: NCT00976131.