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 (PFR(6 months)). Secondary end-points 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%; α = 0.05; β = 0.10). RESULTS:Thirty patients were enrolled. PFR(6 months) 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.
RCT Entities:
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 (PFR(6 months)). Secondary end-points 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%; α = 0.05; β = 0.10). RESULTS: Thirty patients were enrolled. PFR(6 months) 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.
Authors: Vincent T Janmaat; Ewout W Steyerberg; Ate van der Gaast; Ron Hj Mathijssen; Marco J Bruno; Maikel P Peppelenbosch; Ernst J Kuipers; Manon Cw Spaander Journal: Cochrane Database Syst Rev Date: 2017-11-28
Authors: Mariette Labots; Tineke E Buffart; Josien C Haan; Nicole C T van Grieken; Marianne Tijssen; Cornelis J H van de Velde; Heike I Grabsch; Bauke Ylstra; Beatriz Carvalho; Remond J A Fijneman; Henk M W Verheul; Gerrit A Meijer Journal: Cell Oncol (Dordr) Date: 2013-12-31 Impact factor: 6.730
Authors: Michael J Seckl; Christian H Ottensmeier; Michael Cullen; Peter Schmid; Yenting Ngai; Dakshinamoorthy Muthukumar; Joyce Thompson; Susan Harden; Gary Middleton; Kate M Fife; Barbara Crosse; Paul Taylor; Stephen Nash; Allan Hackshaw Journal: J Clin Oncol Date: 2017-02-27 Impact factor: 44.544
Authors: J M Baas; L L Krens; A J ten Tije; F Erdkamp; T van Wezel; H Morreau; H Gelderblom; H J Guchelaar Journal: Invest New Drugs Date: 2015-09-19 Impact factor: 3.850
Authors: Luis Bujanda; Araceli Rodríguez-González; Cristina Sarasqueta; Emma Eizaguirre; Elizabeth Hijona; José J G Marín; María J Perugorria; Jesús M Banales; Angel Cosme Journal: Oncotarget Date: 2016-01-26