Targ Oncol DOI 10.1007/s11523-014-0305-1
ORIGINAL RESEARCH
Sunitinib administered prior to radiotherapy in patients with non-resectable glioblastoma: results of a Phase II study Carmen Balaña & Miguel J. Gil & Pedro Perez & Gaspar Reynes & Oscar Gallego & Teresa Ribalta & Jaume Capellades & Sofia Gonzalez & Eugenia Verger
Received: 31 May 2013 / Accepted: 3 January 2014 # Springer-Verlag France 2014
Abstract Sunitinib is a tyrosine kinase inhibitor with direct anti-tumor and anti-angiogenesis activity targeting VEGFR 1–2, PDGFR α–β, c-kit, bFGF, (CSF-1), FLT3 and RET. The present trial examined the activity of sunitinib in 12 patients with newly diagnosed, non-resectable glioblastoma. Patients (≤75 years of age with performance status [PS] ≥2 and minimental status [MMS] ≥25) were treated post-biopsy C. Balaña (*) Medical Oncology Service, Catalan Institute of Oncology (ICO), Hospital Germans Trias i Pujol, Carretera Canyet sn, 08916 Badalona, Spain e-mail:
[email protected] M. J. Gil Medical Oncology Service, Catalan Institute of Oncology (ICO), IDIBELL Hospital Duran I Reynalds, Gran Via s/n Km 2.7, 08907 L’Hospitalet, Barcelona, Spain P. Perez Medical Oncology Service, Hospital Clinico San Carlos, Calle Profesor Martin Lagos, s/n, 28040 Madrid, Spain G. Reynes Medical Oncology Service, Hospital La Fe, Bulevar del Sur, 46026 Valencia, Spain
with sunitinib 37.5 mg daily for 8 weeks pre-radiotherapy, during radiotherapy (60 Gy, 6 weeks) and post-radiotherapy until disease progression. The primary endpoints were overall response rate (ORR; RANO criteria) after 8 weeks of sunitinib and patient tolerance. Secondary endpoints were percentage of patients free of neurological deterioration pre-radiotherapy, percentage of patients completing radiotherapy, progressionfree survival (PFS), overall survival (OS), and 1-year survival. A Simon 2-stage design (12 →20) based on ORR was applied to calculate the number of patients needed to detect at least 10 % response with α error of 0.05 and β error of 0.10. The trial was closed because it did not meet minimal activity criteria. ORR was 0 % with only 1/12 patients (8.3 %) achieving stable disease after sunitinib treatment. No patient showed reduction in gadolinium enhancement. The most frequent G3/4 toxicities were fatigue (24.9 %) and diarrhea (16.6 %); one patient died of a CNS hemorrhage; 10/12 patients (83.3 %) deteriorated neurologically before radiation therapy; median PFS was 7.7 weeks (95 % CI: 7.2–8.2); median OS was 12.8 weeks (95 % CI: 0.5–23.8 weeks); 1-year survival was 0 %. Sunitinib has no activity as monotherapy in glioblastoma, and further investigation of its efficacy in this setting is unwarranted.
O. Gallego Medical Oncology Service, Hospital de la Santa Creu i de Pau, Calle Sant Antoni M. Claret 167, 08025 Barcelona, Spain
Keywords Glioblastoma . Sunitinib . Radiotherapy
T. Ribalta Department of Pathology, Hospital Clinic Provincial, Calle Villarroel 170, 08036 Barcelona, Spain
Introduction
J. Capellades : S. Gonzalez Radiology Service, Parc de Salut Mar., Hospital del Mar., Passeig Marítim 25-29, 08003 Barcelona, Spain E. Verger Radiotherapy Service, Hospital Clinic Provincial, Calle Villarroel 170, 08036 Barcelona, Spain
The standard treatment of glioblastoma following surgical resection is local irradiation with concomitant administration of temozolomide and subsequent adjuvant temozolomide for 6 cycles. This treatment improved overall survival compared to treatment with irradiation alone (27.2 % vs. 10.9 % at 2 years, 16.0 % vs. 4.4 % at 3 years, 9.8 % vs. 1.9 % at 5 years; hazard ratio, 0.6; p50 %, healed surgical wound, tumor measurable by magnetic resonance imaging (MRI) performed within 3 weeks prior to initiating treatment (MRI acceptable if prior to the biopsy), left ventricular ejection fraction (LVEF) >50 %, adequate bone marrow reserve (neutrophils ≥2,000×109/l, platelets ≥100×109/l, hemoglobin ≥10 g/dl), creatinine
