Sorafenib plus daily low dose temozolomide for relapsed glioblastoma: A phase II study.

Abstract

2080 Background: There are no phase III trials supporting the role of some treatment for relapsed glioblastomas (GBMs). GBMs are very vascularized neoplasms thus antiangiogenic therapies might obtain some antitumoral effects. Recently, an antiangiogenic such as bevacizumab has given prior encouraging results in phase II studies and is under phase III investigation. From phase II studies also low dose protracted temozolomide (LDPT) seems to have some activity at relapse. Basing on these evidences we planned a phase II trial evaluating the activity of a full oral regimen with sorafenib (S), a tyrosine kinase inhibitor with antiangiogenic activity, associated to LDPT in patients (PTS) with relapsed GBMs. Methods: Recruit able PTS (not previously treated with antiangiogenics) were enrolled in the study and received S 400mg bid plus temozolomide (T) 40mg/m2 a day continuously till unmanageable toxicity or disease progression. Disease evaluation were performed every 2 months with gadolinium enhanced MRI using RECIST criteria. Results: From July 2008 to October 2010, 36 patients were enrolled, 18 male, median age was 59.4 (range =36.5-75.6), ECOG PS was 0 in 2 PTS, 1 in 20 PTS and 2 in 14 PTS. All PTS had histological proven GBMs relapsed after surgery, radiotherapy and temozolomide for at least six months. Five PTS had a prior second line chemotherapy and 5 two prior lines of therapy. No PTS received prior antiangiogenic treatment. Toxicity was manageable; grade 1-2 was (Type/PTS): Hand and foot syndrome (HFS)/7, Hypertension/7, Diarrhoea/6, Anorexia/3, fatigue/9, Nausea/4, stomatitis/1, thrombocytopenia/2, anaemia/2 and toxic hepatitis/3; grade 3-4 was HFS/5, hypertension/1, thrombocytopenia/2 and fatigue/2. All PTS were valuable for response: 3 PTS (8.3%) had PR, 16 (44.4%) had SD and 16 had progression. Median TTP was 2.7 months (CI 95% 1.2-4.2) and Median OS was 7.4 months (CI 95% 5.6-9.1). Conclusions: Based on our experience the combination of S ant LDPT is feasible and safe and has some activity against relapsed GBMs. The TTP of present study is comparable to the one obtained treating a similar subset of patients with bevacizumab (Zustovich et al. Anticancer Res. 2010; 12: 5213-6).