Safety and efficacy of the combination of high-dose calcitriol, docetaxel and aoledronic acid in hormone-refractory prostate cancer (HRPC): Interim report of a phase II trial

Abstract

14600 Background: The purpose of this study is to assess the efficacy and safety of Calcitriol, Docetaxel and Zoledronic acid in patients with metastatic HRPC. The primary endpoint of the study is the toxicity profile. Secondary endpoints include prostate specific antigen PSA response and time to disease progression. Methods: 16 patients with HRPC were enrolled. All patients had confirmed diagnosis of prostate cancer and no previous cytotoxic therapy. All patients signed an informed consent. Patients received oral Calcitriol 0.5μg/kg on day 1 on weekly basis six out of eight-week cycles, Docetaxel 36mg/m2 on day 2 on weekly basis six out of eight-week cycles, and Zoledronic acid 4mg intravenously on weeks 1 and 5 of every 8-week cycle. Results: A total of 52 cycles were administered and toxicity was acceptable. No treatment-related mortality was encountered. No grade IV anemia, neutropenia, thrombocytopenia or diarrhea was reported. No grade IV gastrointestinal toxicities or thromboembolic events were reported. Grade IV infection was seen in 2 (3.8%) cycles (herpetic esophagitis and listeria meningitis). Grade III neutropenia was seen in 2 cycles (3.8%). Grade III diarrhea was seen in 1 cycle (1.9%) and grade II diarrhea in 4 cycles (7.7%). Grade II to III nausea and vomiting was reported in 8 cycles (15.4%). Grade II to III sensory neuropathy was noted after 17 cycles (32.7%). Grade III fatigue was reported in 5 cycles (9.6%). 14 patients were eligible for response analysis. Overall PSA response rate of our patients was 57.2%. Median time to disease progression was 6.5 months (range 2–15). One year survival was 57.1% (8 out of 14 patients). Conclusions: This interim analysis showed that the addition of Calcitriol to Docetaxel showed an acceptable safety profile as compared to Docetaxel regimens alone with less incidence of neutropenia and diarrhea. Previous studies using Docetaxel alone has reported higher incidence of neutropenia reaching 43–56% and grade III to IV diarrhea (10–34%). Our study suggests that Calcitriol might have a protective effect against the Docetaxel toxicities. No significant financial relationships to disclose.