Login to Access Video or Poster Abstract: MP41-11
Sources of Funding: none

Introduction

We previously reported a novel cell reprogramming approach, termed drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs targeting the cancer stemness-related gene network, and identified ribavirin as a candidate drug for overcoming docetaxel-resistant castration-resistant prostate cancer (CRPC). This nonrandomized, open-labeled pilot clinical study explored the safety and efficacy of ribavirin, an antiviral drug, in combination with docetaxel in patients with progressive CRPC.

Methods

In this clinical study, patients received intravenous docetaxel 60–70 mg/mm2 on day 1 of 3–6-week cycles plus ribavirin 600 mg twice daily. The primary endpoint was safety, prostate-specific antigen (PSA) response and objective response rate. Secondary endpoints included health-related quality of life and overall survival. Patients with progressive CRPC based on PSA and/or radiographic criteria, performance status (PS) 0–1, and normal renal and hepatic function were eligible.

Results

Five patients were enrolled in this study; medium age was 73. Median serum PSA concentration was 53.1 ng/ml (range: 5.1–370.5). The median cycle and total dose of docetaxel received before the study was 31 cycles and 3625 mg, respectively. Overall, 80% of patients had disease progression during docetaxel treatment. The median time from last docetaxel dose to disease progression before participation was 1.5 months. Safety: median number of treatment cycles were 7 (range: 3–8) cycles. Grade 3/4 adverse events requiring dose modification were not observed. Grade 3 anemia and neutropenia were seen in two patients. Common adverse events were less than Grade 2. Efficacy: 3 (60%) patients had some degree of PSA decline and 2 (40%) had a decline of ?30%. Median follow-up was 10.0 months. Median progression-free survival was 6 months.

Conclusions

This combination of ribavirin with docetaxel was well tolerated with a promising response rate that justifies further investigations in docetaxel-resistant CRPC. This clinical study provides a useful drug re-positioning model in the area of translational medicine.

Funding

none