Temozolomide (TMZ) 1 week on/1 week off as initial treatment for progressive low grade oligodendroglial tumors: A phase II AINO study.

2019 Background: Protracted low dose TMZ offers potential advantages over standard TMZ, including greater cumulative drug exposure and depletion of MGMT. Few data are available on the efficacy and tolerability of protracted low dose TMZ in patients with low grade gliomas.,In this ongoing phase II study, patients with progressive low grade oligodendroglial tumors after surgery are eligible. TMZ is administered orally at 150 mg/m/d, days 1-7 and 15-21 every 4 weeks, up to 18 cycles or tumor progression or unacceptable toxicity. Patients undergo clinical and MRI assessment every 4 and 8 weeks respectively, and a monitoring by PET with methionine (every 6 month) is performed in selected centers. The primary endpoint is response (based on FLAIR sequences), and secondary endpoints are progression free-survival (PFS) at 6 mos and 12 mos, median PFS, quality of life and toxicity. The analysis of 1p/19q status by FISH and MGMT promoter methylation by PCR are mandatory.,Of the first 31 patients enrolled since 2005, 25 are evaluable for response (median age 41, median KPS 90, and 36% with mild enhancement on MRI). Pathological diagnosis was oligodendroglioma (15) and oligoastrocytoma (10).The response rate was 52% (13/25) with PR 32% and MR 20%, and disease control rate (PR+MR+SD) was 92%. Median time to maximum radiographic response was 6 months; 2 patients had an early response (within the first 2 months), whereas 1 patient had a delayed response up to 6 months after interruption of treatment. Eleven of 17 (65%) patients improved, particularly those with seizures. Twenty of 25 patients are free from progression with a median follow-up of 14 months (range 4-39). Combined 1p/19q or isolated 1p deletion was not associated with response on FLAIR images, but only with response of the enhancing tumor. Grade 3 lymphopenia was observed in 45% of patients, and 15% interrupted the treatment or were changed to standard TMZ.,TMZ 1 week on/1 week off, as initial treatment for progressive low grade oligodendroglial tumors, seems more efficacious than standard dose TMZ, and is relatively safe. Updated results, correlation between MGMT promoter methylation, 1p/19q loss and response, and monitoring with PET will be presented. No significant financial relationships to disclose.