Temozolomide treatment for newly diagnosed anaplastic oligodendrogliomas: a clinical efficacy trial

Abstract

Purpose: Chemotherapy with alkylating agents is of proven efficacy in recurrent anaplastic oligodendroglioma (AO) with reported response rates ranging between 50% and 70%. The response of newly diagnosed AO to initial treatment with temozolomide (TMZ) has not yet been reported. This study evaluated the response and time to tumor progression of newly diagnosed AO initially treated with TMZ.

Patients and methods: Twenty patients with a median age of 47 (range: 26-65) received a median of 14 (range: 3-24) cycles of TMZ as their first modality of therapy following diagnosis of AO. Treatment was given every 28 days for 5 days at a starting dose of 200 mg/m2/d and was continued for 24 cycles unless toxicity or tumor progression required withdrawal of TMZ. MRI evaluations were repeated every 8 weeks and scales of Karnofsky performance status (KPS) and of neurological function were used to assess clinical response.

Results: Clinical improvement was observed in 60% of the patients with statistically significant gain measured by KPS and the neurologic function scales. The objective response rate was 75%, and median time to tumor progression was 24 months. Maximal objective response was reached within a median of 6 months (range: 3-12). Tumors with 1p loss had longer progression free survival compared to tumors without deletions (PFS at 24 months: 1p LOH = 100%, 1p intact = 20%; P = 0.057). TMZ was well tolerated with only two events of grade 3/4 hematological toxicity.

Conclusions: Newly diagnosed AO demonstrates a high rate of response to initial therapy with TMZ, similar to the response reported for PCV combination therapy. Further studies are needed to determine the optimal duration of treatment and whether radiotherapy should immediately follow chemotherapy.