Chemotherapy plus concomitant low-dose fractionated radiotherapy as second-line treatment for recurrent or progressive glioblastoma after temozolomide-based chemoradiation: A pilot study.

2083 Background: Second-line treatment in recurrent or progressive glioblastoma (GBM) has not yet been defined. Since in vitro and preclinical studies demonstrated a hyper-radiosensitivity of human malignant glioma cell lines to low doses fractionated radiotherapy (LD-FRT) and a synergism with chemotherapy, we performed a pilot study to evaluate the feasibility and efficacy of this approach. METHODS Eligibility criteria were: radiological diagnosis of recurrent or progressive GBM, previously treated by surgical resection followed by 3D-CRT (total dose 59,4 Gy) plus concomitant and adjuvant TMZ. Patients with recurrent or progressive disease during adjuvant TMZ received 30 cGy twice a day on days 1-2,8-9,15-16, q42, concurrently with fotemustine (40 mg/m2 on days 1, 8, 15) and cisplatin (30 mg/m2 on days 2, 9, 16), whereas in patients with recurrent/progressive disease occurring more than 6 months after the end of adjuvant TMZ a re-challenge with TMZ (150/200 mg/m2) concurrently with LD-FRT (40 cGy twice a day, over consecutive 5 days, q28) was attempted. Primary endpoints were toxicity (RTOG criteria) and efficacy (RECIST criteria); Progression Free Survival (PFS) and Overall Survival (OS) were also evaluated. RESULTS From February 2008 to January 2011, 20 patients were enrolled. The median total dose of LD-FRT was 760 cGy (range, 240-1200). The associated chemotherapy was based on cisplatin and fotemustine in 7 patients and on TMZ in 13 patients. Hematologic toxicity was mild, with a G3-4 (leucopenia) observed in 5% of patients; no treatment related death was observed. One out of 20 patients (5%) had a complete response, 1 patient (5%) experienced a partial response (PR), while 5 patients (25%) had a stable disease (SD) lasting at least 8 weeks (Clinical Benefit 35%). The median PFS and OS from relapse were 5 and 7 months, respectively; survival rate at 6 months was 58.7 % with an OS at 1 year of 26.7 %. No differences were observed between the two schedules of chemotherapy. CONCLUSIONS These data suggest that chemotherapy plus LD-FRT as second-line treatment is safe and well tolerated, encouraging the prosecution of the study.