A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas
Mené sur 39 patients atteints d'un adénocarcinome avancé des voies biliaires, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du sorafenib à un traitement combinant gemcitabine et cisplatine
Background: This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy. Methods: Patients with advanced biliary adenocarcinomas received gemcitabine 1000mgm−2 and cisplatin 25mgm−2 on a 2 weeks on/1 week off cycle and sorafenib 400mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand–foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800mgm−2, cisplatin 20mgm−2 and sorafenib 400mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57–77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome. Results: A total of 39 patients were accrued. The most common grade 3–4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34–66%). Median PFS and overall survival were 6.5 (95% CI: 3.5–8.3) and 14.4 months (95% CI: 11.6–19.2 months), respectively. No correlation was observed between pERK and outcomes. Conclusion: The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.