Addition of continuous low dose temozolomide (T) to bevacizumab (Bev) plus irinotecan (Iri) after bevacizumab plus irinotecan failure in heavily pretreated glioblastoma multiforme (GBM)

Abstract

e13015 Background: In several phase II studies in relapsed GBM, Bev plus Iri showed impressive objective response rates (>50%) with acceptable toxicity rate, duration of response, however, was moderate. Methods: From April 2007 to October 2008, 35 pretreated patients with confirmed GBM with progressive disease (PD) after Bev (4 mg/kg body weight i.v.) plus Iri (80 mg/m2 i.v.) were treated with additional continuous low dose T (20 mg per day p.o.) while Bev plus Iri were continued. ECOG performance status (PF) was 0 - 2 in all pts. MRI scan was required after 4 weeks and every 6 weeks afterwards. MacDonald criteria were used for evaluation of response. If MRI scans could not be performed, patients were considered to have PD. Treatment was given until PD or intolerable toxicity occurred. Results: All 35 patients were eligible for toxicity and efficacy, median follow up was 7 months (2 - 20), 25 patients were male, 10 female, median age was 51 years (29 - 80), 21 patients had primary GBM, 14 patients secondary GBM. All patients had prior irradiation (56 - 60 Gy) 2 patients had 5, 8 patients had 4, 15 patients had 3, and 10 patients 2 prior chemotherapeutic regimen. 1 patient developed grade 3 leucopenia, and 1 patients grade 3 thrombopenia; 3 patients asymptomatic intracerebral bleeds requiring treatment delay, 1 pat. grade 3 sepsis and 2 patients grade 3 fatigue. In 4/35 patients a partial response (PR) was achieved, in 14/35 patients a disease stabilization for at least 2 months, while 17/35 patients showed primary PD. Median duration of PR was 3.5 months (2–5), median duration of SD was 5 months (2–13), Median survival was 5 months (2–13). Data will be updated. Conclusions: The addition of continuous low dose T in combination with Bev plus Iri seems to have activity in GBM patients, after progression on Bev plus Iri treatment, and has an acceptable toxicity profile. Further investigation of the combination Bev plus Iri plus T in GBM patients is necessary. No significant financial relationships to disclose.