Ascorbic acid plus gemcitabine (gem) and erlotinib (erl) in patients with metastatic pancreatic cancer (mPanc): Preliminary safety results.

Abstract

e14659 Background: Intravenous ascorbic acid in pharmacologic concentrations, via production of extracellular hydrogen peroxide and reactive oxygen species, has selective cytotoxicity to cancer cells but not normal cells and tissues in vitro and in vivo. In this study we have evaluated safety and tolerability of ascorbic acid combined with gem/erl in patients with mPanc, and we now report preliminary safety results. Methods: This is the phase I, open label portion of a phase I/II trial. The primary objective is to determine safety and tolerability of intravenous ascorbic acid at three dosage levels with gem/erl. The secondary objective is to evaluate tumor free progression. Eligible patients were >18 yrs of age, life expectancy > 3 months, histologically confirmed mPanc and ECOG PS 0/1. All patients received intravenous ascorbic acid at three times weekly combined with gem 1,000 mg/m2 weekly for 7 weeks and erl 100 mg oral daily. After a week of rest and reevaluation, subsequent cycles consisted of gem 1,000 mg/m2 weekly times 3 with 1 week of rest. The study used a 3+3+3 design with three different ascorbic acid doses: 50 gm, 75 gm, and 100 gm infused over 90-minute duration. Safety and tolerability is based on dose-limiting toxicities (DLTs), and grade 3/4 combination chemotherapy related adverse events (AEs) deemed clinically significant by the investigator. Plasma levels of ascorbic acid, gem, and erl will be determined. The primary endpoint was incidence of DLTs. Results: No DLT has been reported for the first 5 DLT evaluable subjects. Accrual to part 1 continues. Five patients have enrolled in part 1; 4 patients were female. Mean age was 69 years (60-82); ECOG 0/1 = 4/1. No grade 4 or 5 treatment related DLTs were seen. Serious possible AEs included diarrhea (grade 3) in one pt and jaundice (grade 3) in 1 pt. One pt had partial response, 2 pts had stable disease, and 2 pts had disease progression. Conclusions: Ascorbic acid combined with gem/erl has been well tolerated and may in the future offer potential in pts with mPanc. The MTD has not yet been reached. Treatment-related AEs Number of pts Grade of toxicity Nausea/vomiting 1 1 Infection 0 Diarrhea 2 1, 3 Erythema 1 1 Thrombocytopenia 2 1, 2 Rash 1 1 Jaundice 1 3 No significant financial relationships to disclose.