Phase II Randomized Study of Whole-Brain Radiation Therapy with or without Concurrent Temozolomide for Brain Metastases from Breast Cancer
Mené sur 100 patientes présentant des métastases cérébrales ayant pour origine un cancer du sein (âge médian : 55 ans ; durée médiane de suivi : 9,4 mois), cet essai de phase II évalue, du point de vue du taux de réponse objective à 6 semaines, de la survie sans progression et de la survie globale, l'efficacité d'une radiothérapie du cerveau entier avec ou sans chimiothérapie concomitante par témozolomide
Background : To improve the therapeutic index of whole-brain radiation therapy (WBRT) in the treatment of brain metastases from breast cancer, we investigated the efficacy and safety of WBRT combined with temozolomide (TMZ) in this population. Patients and Methods : This phase II multicenter prospective randomized study included patients with newly diagnosed intraparenchymal brain metastases from breast cancer, unsuitable for surgery or radiosurgery. All patients received conformal WBRT (3 Gy x 10 to 30 Gy), with or without concomitant TMZ administered at a dosage of 75 mg/m2/day during the irradiation period. The primary endpoint was objective response rate six weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (modified WHO criteria). Secondary endpoints were progression-free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability. Results : Between February 2008 and November 2010, 100 patients were enrolled in the study (50 in the WBRT+TMZ arm, 50 in the WBRT arm). Median age was 55 years [29 -79]. Median follow-up was 9.4 months [1.0 – 68.1]. Objective responses rates at six weeks were 36% in the WBRT arm and 30% in the WBRT+TMZ arm (NS). In the WBRT arm, median PFS was 7.4 months and median OS was 11.1 months. In the WBRT+TMZ arm, median PFS was 6.9 months and median OS was 9.4 months. Treatment was well tolerated in this arm: the most common≥grade 2 acute toxicity was reversible lymphopenia. Conclusion : Whole-brain radiation therapy combined with temozolomide did not significantly improve local control and survival in patients with brain metastases from breast cancer. Clinicaltrials.gov registration number NCT00875355
Annals of Oncology 2014