Extended Adjuvant Temozolomide with cis-Retinoic Acid for Adult Glioblastoma

Objective: To determine the toxicity and effectiveness of 24 months of adjuvant temozolomide (TMZ) with cis-retinoic acid (CRA) for patients with glioblastoma. Methods: This retrospective population-based review considered the charts of all patients diagnosed with glioblastoma in Manitoba and referred to a provincial cancer centre during 2002–2008. Consecutive patients came from a population-based referral centre and provincial cancer registry. All patients were treated according to the local standard of care with surgical resection followed by concurrent radiotherapy and TMZ 75 mg/m² daily, followed by TMZ 150–200 mg/m² for days 1–5, repeated every 28 days for up to 24 cycles, and CRA 50 mg/m² twice daily for days 1–21, repeated every 28 days. The main outcome measures were safety, tolerability, and effectiveness of long-term TMZ and CRA. Results: Of 247 patients diagnosed with glioblastoma in Manitoba during the study period, 116 started concurrent chemoradiotherapy, and 80 received adjuvant TMZ. Of the patients who started concurrent chemoradiotherapy, 80 began adjuvant chemotherapy. Patients completed a median of 5.5 cycles of TMZ and 3 cycles of CRA. Grade 3 or 4 hematologic toxicity was noted in 16% of patients. Median overall survival was 15.1 months, and 26.7% of patients remained alive at 2 years. Conclusions: Extended adjuvant TMZ and CRA is well tolerated. However, the population-based effectiveness of this regimen is similar to the clinical trial efficacy of 6 months of adjuvant TMZ. Future studies in glioblastoma should incorporate duration of adjuvant chemotherapy into the study design.