Intravenous vitamin C as an adjunct to standard therapy in pancreatic ductal adenocarcinoma: A systematic review of clinical trials.

Abstract

e16396 Background: Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer death, with a 5-year survival rate of just 13%. Vitamin C shows promise in PDAC by generating hydrogen peroxide (H₂O₂), selectively targeting cancer cells, and enhancing chemo- and radiosensitivity. This study aims to explore Vitamin C’s therapeutic potential in PDAC. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted on PubMed, Cochrane, Clinicaltrials.gov, and Embase databases from inception until January 2025 using MeSH terms and keywords related to "pancreatic cancer" and "vitamin C." Out of 345 search results, five clinical trials (four phase I and one Phase II) on PDAC were included, investigating Vitamin C's therapeutic potential and its impact on treatment outcomes. The selected studies were systematically reviewed and described. Results: Five clinical trials involving 62 patients with PDAC (44% male, median age 61 years [range: 48–75]) were analyzed. Four trials focused on metastatic PDAC, and one on locally advanced, borderline-resectable disease. Only one trial included a control arm. Intravenous Vitamin C, most commonly 75g three times weekly (range: 50–100 g, up to twice weekly), was added to standard-of-care regimens. All trials incorporated gemcitabine-based chemotherapy, either alone (two trials), with nab-paclitaxel (one trial), with erlotinib (one trial), or alongside radiation therapy in borderline-resectable PDAC. Median progression-free survival (PFS) ranged from 3.0 to 13.7 months (mean: 6.4 months), and median overall survival (OS) ranged from 6.0 to 21.7 months (mean: 14.4 months). Notably, two borderline-resectable PDAC patients, previously deemed inoperable after FOLFIRINOX, underwent curative-intent surgery following gemcitabine and concurrent radiotherapy with Vit C. Over 50% of trials reported improved PFS and OS compared to historical or institutional data. Treatment completion rates increased by > 30% for chemotherapy and > 70% for radiation therapy. Vit C was well tolerated, with common adverse effects being nausea, lightheadedness, and dry mouth; only one grade 3 event (hypertension) was reported, and no dose-limiting toxicities occurred. Most grade ≥3 adverse effects were related to chemotherapy or disease progression, including cytopenia, transaminitis, electrolyte imbalances, fever, and pulmonary embolism. Conclusions: This systematic review indicates that adding intravenous Vitamin C to standard chemotherapy and/or radiation therapy may enhance survival outcomes and treatment tolerance in PDAC patients with minimal added toxicity. These promising findings highlight the need for large-scale clinical trials to confirm Vitamin C's role in PDAC management.