The addition of pravastatin to chemotherapy in advanced gastric carcinoma: A randomised phase II trial

Purpose: Statins have for long been considered to play a potential role in anticancer treatment based upon their ability to inhibit the mevalonate synthesis pathway. This randomised phase II trial compared the efficacy and safety of pravastatin added to epirubicin, cisplatin and capecitabine (ECC versus ECC + P) in patients with advanced gastric carcinoma. Methods: Patients were randomised to receive up to six cycles of 3-weekly ECC with or without pravastatin (40 mg, once daily from day 1 of the first cycle until day 21 of the last cycle). Primary end-point was progression-free rate at 6 months (PFR6months). Secondary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) and safety. For early termination in case of futility, a two-stage design was applied (P-0 = 50%; P-1 = 70%; alpha = 0.05; beta = 0.10). Results: Thirty patients were enrolled. PFR6months was 6/14 patients (42.8%) in the ECC + P arm, and 7/15 patients (46.7%) in the control arm, and therefore the study was terminated after the first stage. In the ECC and ECC + P arm, RR was 7/15 (46.7%) and 5/15 (33.3%), median PFS was 5 and 6 months and median OS was 6 and 8 months, respectively. Toxicity data showed no significant differences, although there was a trend towards more gastrointestinal side-effects such as diarrhoea and stomatitis in the ECC + P arm. Conclusion: In this randomised phase II trial the addition of pravastatin to ECC did not improve outcome in patients with advanced gastric cancer. Therefore, further testing of this combination in a randomised phase III trial cannot be recommended. (C) 2010 Elsevier Ltd. All rights reserved.