Document Type

Article

Publication Date

8-1-2024

Comments

This article is the author's final published version in Cancer Research Communications, Volume 4, Issue 8, August 2024, Pages 2174 - 2182.

The published version is available at https://doi.org/10.1158/2767-9764.CRC-24-0225.

Copyright © 2024 The Authors

Abstract

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate instrument. Correlative analyses included pharmacokinetics and oxidative stress markers. Eighty-nine percent of patients previously had three or more lines of therapy. The PSA50 response rate was 41% in the HDIVC group and 33% in the placebo group (P = 0.44), with comparable adverse event rates in both groups. There were no significant differences in Functional Assessment of Cancer Therapy-Prostate scores. The median radiographic progression-free survival was not significantly different between the HDIVC and placebo groups, with durations of 10.1 and 10.0 months (HR, 1.35; 95% confidence interval, 0.66-2.75; P = 0.40), respectively. The median overall survival was 15.2 months in the HDIVC group and 29.5 months in the placebo group (HR, 1.98; 95% confidence interval, 0.85-4.58; P = 0.11). HDIVC did not decrease F2-isoprostanes, indicators of oxidative stress. The study was suspended after prespecified interim analysis indicated futility in achieving primary endpoints. In this patient population, combining HDIVC with docetaxel did not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. Findings do not support the routine use of HDIVC in mCRPC treatment outside of clinical trials.

SIGNIFICANCE: This is the first randomized, placebo-controlled, double-blind trial to evaluate HDIVC in cancer treatment. The addition of HDIVC to docetaxel in patients with mCRPC does not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. The routine use of HDIVC in mCRPC treatment is not supported outside of clinical trials.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Additional Files
Supplementary Methods.docx (58 kB)
Table S1.docx (15 kB)
Table S3.docx (13 kB)
Table S2.docx (14 kB)
Table S4.docx (13 kB)
Table S5.docx (16 kB)
Table S6.docx (15 kB)
Table S7.docx (15 kB)
Table S8.docx (3125 kB)
Table S9.docx (13 kB)
Table S10.docx (15 kB)
Table S11.docx (14 kB)
Table S12.docx (14 kB)
Table S13.docx (15 kB)
Table S14.docx (13 kB)
Table S15.docx (13 kB)
Table S16.docx (13 kB)
Table S17.docx (12 kB)
Figure S1.docx (126 kB)
Figure S2.docx (66 kB)
Supplementary Trial Protocol.pdf (664 kB)

PubMed ID

39076107

Language

English

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