Abstract 1833P
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.
Resources from the same session
1820P - Cardiovascular effects of androgen receptor signalling inhibitors in the treatment of advanced and metastatic prostate cancer: A systematic review and meta-analysis of randomised controlled trials
Presenter: Omar El-Taji
Session: Poster session 15
1821P - High serum FSH/T ratio as a marker for the development of cardiovascular disease in ADT recipients
Presenter: Jehonathan Pinthus
Session: Poster session 15
1822P - PSMA-alpha targeted radionuclide therapy (TRT) with or without prior PSMA-beta TRT
Presenter: Michael Sun
Session: Poster session 15
1823P - The impact of baseline PSMA PET/CT vs. CT on outcomes of Radium-223 therapy in mCRPC patients
Presenter: Dianne Bosch
Session: Poster session 15
1824P - Treatment patterns among novel hormonal therapy-experienced patients with metastatic castration-resistant prostate cancer
Presenter: Vivek Narayan
Session: Poster session 15
1825P - Molecular features of circulating tumour cells (CTCs) associate with response to 177Lu-PSMA-617 plus pembrolizumab for metastatic castration resistant prostate cancer (mCRPC)
Presenter: David Goode
Session: Poster session 15
1826P - Lutetium-177-PSMA in pre- and post-taxane mCRPC setting: Results from a phase II clinical trial
Presenter: Emilio Giunta
Session: Poster session 15
1827P - Real-world (RW) overall survival (OS) with enzalutamide (ENZ) and abiraterone acetate (ABI) in patients (pts) with chemotherapy (cx)-naïve metastatic castration-resistant prostate cancer (mCRPC)
Presenter: Daniel George
Session: Poster session 15
1828P - ARX517: A next generation anti-PSMA antibody drug conjugate (ADC) demonstrates notable stability and pharmacokinetic (PK) profile in the ARX517 phase I clinical trial (APEX-01)
Presenter: Scott Tagawa
Session: Poster session 15
1829P - Exposure-safety analyses of talazoparib in combination of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) in TALAPRO-2 trial
Presenter: Arun Azad
Session: Poster session 15