1833P - Concurrent high-dose IV Vitamin C (IVC) and docetaxel for metastatic castrate-resistant prostate cancer (mCRPC): A randomized, placebo-controlled, double-blind phase II trial

Background

Integrative medicine practitioners offer high-dose IVC for cancer treatment, but its incorporation into clinical practice has sparked controversy and remains an active area of investigation. While preclinical studies have shown that IVC may have anti-cancer effects in prostate cancer models, evidence from clinical research is limited. While several clinical trials showed that IVC is well tolerated, can reduce toxicities, and may improve quality of life (QoL), uncertainties remain. Here we investigated if combining IVC with docetaxel could improve the prostate-specific antigen (PSA) response rate in patients with mCRPC and could mitigate docetaxel toxicities.

Methods

We randomized (2:1) patients with mCRPC who progressed despite androgen receptor-targeted therapy to receive docetaxel (75mg/m² IV every 3 weeks) with IVC (1g/kg) (n=32) or placebo twice/week (n=15). Primary endpoints were PSA50 response by 24 weeks and adverse events (AEs) of fatigue, nausea, bone pain, and anorexia. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and QoL measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P).

Results

PSA response rate was 41% in the vitamin C and 33% in the placebo group, with no statistically significant difference (p=0.44). Grade 1-2 and grade 3-4 AEs occurred in 69% and 6% vs 60% and 0% of patients, respectively (one-sided Cochran Armitage test, p=0.90). FACT-P was not significantly different at any timepoints. Median rPFS was 10.1 months (95% CI, 5.85, 14.7) vs 10.0 months (95% CI: 5.32, NA), HR 1.35 (95% CI, 0.66-2.75, p=0.40). Median OS was 15.2 months (95% CI, 13.2-25.3) vs 29.5 months (95% CI, 18.1-NA; HR 1.98 [95% CI 0.85-4.58], p=0.11). The median PFS (modified PCWG2 definition) was 5.5 months vs 8.4 months (HR 1.19 [95% CI 0.60-2.38], p=0.62).

Conclusions

Concurrent high-dose IV vitamin C did not improve PSA response, toxicity, or clinical outcomes in mCRPC patients receiving docetaxel.

Clinical trial identification

NCT02516670.

Editorial acknowledgement

Legal entity responsible for the study

C. J. Paller.

Funding

The work was supported in part by the National Institute of Health grants: T32GM066691 (DAG). The project described was also supported by the Analytical Pharmacology Core of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (NIH P30CA006973 (M.A.R.) and UL1TR003098 (M.A.R.), Shared Instrument Grant S10RR026824 (M.A.R.). Grant Number UL1TR003098 is from the National Center for Advancing Translational Sciences (NCATS), a component of the NIH, and NIH Roadmap for Medical Research.

Disclosure

All authors have declared no conflicts of interest.