Randomized placebo-controlled trial of intravenous vitamin C plus docetaxel in metastatic prostate cancer.
Year: 2023
Type: conference-abstract
Abstract: e17050 Background: Some phase I/II trials showed that combining high dose IV vitamin C with chemotherapies decreased toxicities and improved QoL in advanced cancers, while others failed to show benefits. While grade ¾ AEs are not typically a co-primary endpoint, they are a measure of cumulative toxicity. We investigated whether high-dose IV vitamin C could improve prostate-specific antigen (PSA) response rate and mitigate docetaxel toxicities in patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving docetaxel. Methods: Patients were randomized (2:1) to receive docetaxel (75mg/m2 IV every 3 weeks) plus IV vitamin C (1g/kg) or placebo twice a week. The primary endpoints were PSA50 response by24 weeks and adverse events (AEs) of fatigue, nausea, bone pain, and anorexia. Secondary endpoints included overall survival (OS) and QoL measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Results: 50 patients were randomized, 47 received therapy (treatment N = 32, control N = 15), 3 untreated (withdrawal, elevated creatine, low hemoglobin). The median age was 74 years (range 45-85) and ECOG 1. The median PSA was 108.3 ng/mL (range: 0.3, 2102.3). The median number of chemotherapy cycles was 6 (IQR 3-8). The study was suspended after the pre-specified interim analysis for primary endpoints showed futility. The PSA50 response was 41% for treatment and 33% for control (P = 0.44). Grade 1-2 and grade 3-4 prespecified AEs occurred in 69% and 6% of treatment group patients versus 60% and 0% of control group patients (one-sided Cochran Armitage test, P =0.90). Diarrhea (72% vs 19%) and anemia (47% vs 25%) and neutropenia (22% vs 19%) are more frequent in the Vit C group. Compared with the control group, treatment group patients showed a trend towards shorter median OS. FACT-P was not significantly different at any timepoints. Conclusions: Initial concurrent high-dose IV vitamin C with docetaxel did not improve PSA response, toxicity, or clinical outcomes. MCRPC patients receiving docetaxel should be advised against seeking concurrent high-dose IV vitamin C. Clinical trial information: NCT02516670 .
Source: Journal of Clinical Oncology
Authors: Channing Judith Paller, Marianna Zahurak, Elisabeth I. Heath, William Kevin Kelly, Christopher J. Hoimes, Jason David Taksey, Catherine Handy Marshall, Mark Christopher Markowski, Pedro C. Barata, Michelle A. Rudek, Julie Nauroth, Lin Wang, Jennifer N. Durham, Mario A. Eisenberger, Michael Anthony Carducci, Samuel R. Denmeade, Mark Levine
Institutions: Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, Wayne State University, The Barbara Ann Karmanos Cancer Institute, Thomas Jefferson University, Duke Medical Center, Maryland Oncology Hematology, University Hospitals Cleveland Medical Center, Johns Hopkins Hospital, National Institutes of Health
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Marcus Foundation
OpenAlex ID: W4379330883