A phase II trial of high-dose calcitriol and docetaxel in patients with untreated, incurable pancreatic adenocarcinoma

Abstract

15099 Background: Taxanes have activity in patients with advanced pancreatic adenocarcinoma. In preclinical studies, calcitriol, the active form of vitamin D, potentiates docetaxel-induced cell death in pancreatic and prostatic cancer cell lines. Clinically, single institution and randomized prostate cancer trials using weekly high-dose calcitriol with docetaxel have demonstrated high PSA response rates (J Clin Oncol 2003, 2007). Herein we report results from a phase II study of the identical regimen in patients with incurable pancreatic adenocarcinoma. Methods: Patients with a histologic diagnosis of locally advanced or metastatic pancreatic adenocarcinoma, Zubrod PS 0–2, and adequate organ function were eligible. Previous non-docetaxel adjuvant chemotherapy and radiation were permissible. Patients received calcitriol 0.5 mcg/kg orally day 1, followed by docetaxel 36 mg/m2 on day 2. Therapy was given weekly for 3 weeks, followed by a 1 week break, and patients were treated until progression. The primary endpoint was time-to-progression (TTP). Results: 24 patients with metastatic and 1 with locally advanced (25 total) were enrolled, treated and are evaluable for efficacy and toxicity. Median age and PS were 60 (range 30 to 79) and 1, respectively. 68% were males, and all were white. Three patients are alive and 22 have died. The median number of cycles was 1 (range 0 to 12). 3 patients (12%, 95% CI 3 to 31) achieved a partial response, and 7 (28%) stable disease for at least 7 weeks. Median TTP and median overall survival were 2.2 and 5 months respectively. Potentially treatment-related common grade 3/4 toxicities included: thrombosis -12%, abnormal LFTs-16%, nausea-8%, fatigue-16%, infection-12%, neutropenia/leucopenia-16%, effusion-8%, abnormal electrolytes-24%, and infusion reaction-4%. Conclusions: The combination of docetaxel and high-dose calcitriol has activity in pts with advanced pancreatic cancer, but the regimen offers no apparent advantage over historical results achieved with standard gemcitabine. No significant financial relationships to disclose.