A multicenter phase 2 consortium (P2C) study of triapine in patients (pts) with advanced adenocarcinoma of the pancreas.

14118 Background: Triapine is a small molecule iron chelator that has been shown to inhibit ribonucleotide reductase (RR) at the M2 subunit. Early trials suggested activity in pancreatic cancer. The P2C initiated a study of single agent Triapine as both first-line therapy and for pts with gemcitabine-refractory disease. Correlatives included: pharmacokinetics, MDR polymorphisms, and the effects of Triapine on cell cycle and electron paramagnetic resonance spectroscopy (EPR).,Standard eligibility criteria were used, however, pts with G6PD deficiency were excluded. Triapine was given 96 mg/m IV over 2 hours, days 1-4 and 15-18, repeated q 28 days. Primary goals - evaluate survival (S) at 6 mos (previously untreated pts) and 4 mos (refractory pts). Interim analyses were planned when 28 previously untreated and 20 refractory pts were enrolled.,14 eligible pts were enrolled in 10 mos (13 refractory, 9 male). The previously untreated pt received only 1 cycle secondary to progressive disease. Of the 13 refractory pts, 7 pts received at most 2 cycles; 6 received 1. Disease progression precluded further treatment in 11 pts. 6 pts had Gr 4 toxicities at least possibly related to drug, including: neutropenia-4, hyperkalemia-1, hyponatremia-1, leukopenia-1, thrombocytopenia-1, hypophosphatemia-1. 6 pts had a Gr 3 fatigue. One refractory patient expired on study. No responses were seen. Estimated 4 mos S in refractory pts is 16% (95% CI 3-94). EPR studies showed that Triapine led to a loss of the RR tyrosine radical EPR signal.,Enrollment was suspended due to excess toxicity and lack of activity in pts refractory to gemcitabine. Correlative studies confirm the mechanism of action of Triapine as a chelating agent on RR. Supported by NCI Grant N01 CM17104 and the NCI Translational Research Fund. No significant financial relationships to disclose.