Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial.
Level 4 - case-series / case-control
Phase I single-arm dose-escalation safety study (case series design)
PubMed 23381814 · doi:10.1007/s00280-013-2070-8
What was done
A phase I dose-escalation trial evaluated the safety and tolerability of intravenous pharmacological ascorbate combined with standard gemcitabine in 9 patients with biopsy-proven stage IV pancreatic adenocarcinoma. Ascorbate was administered twice weekly (15–125 g) using Simon's accelerated titration design to reach a target post-infusion plasma concentration of ≥350 mg/dL (≥20 mM). Monitored outcomes included adverse events, disease burden, weight, performance status, hematologic/metabolic labs, time to progression, and overall survival.
What was found
Mean plasma ascorbate trough levels increased significantly compared to baseline (1.46 ± 0.02 vs. 0.78 ± 0.09 mg/dL; 83 vs. 44 μM, p < 0.001). Treatment-related adverse events included dry mouth (n = 6) and diarrhea (n = 4), with no dose-limiting toxicities met. For subjects completing at least two 8-week cycles of therapy, mean overall survival was 13 ± 2 months.
Why it matters
This phase I study establishes preliminary feasibility and safety for combining high-dose intravenous ascorbate with gemcitabine in advanced pancreatic cancer. It provides pharmacokinetic and safety benchmarks to support larger, controlled efficacy trials.
Limits
The sample size is extremely small (n = 9), lacking a control group or randomization. Survival results are descriptive and potentially subject to immortal time or selection bias, as survival was only reported for patients completing at least two treatment cycles. Efficacy cannot be determined from this study design.
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