1. In grade 2 glioma patients younger than 40 years old that have undergone subtotal tumour resection, or in patients 40 years of age and older, the combination of chemotherapy and radiation confers a longer progression-free and overall survival compared to radiation therapy alone.
2. The frequency and severity of toxicity was greater in the radiation plus chemotherapy arm, with most side effects being of grade 1 or 2 in nature. There were no grade 5 toxic effects, or instances of myelodysplasia or leukemia.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Grade 2 gliomas are relatively uncommon primary adult brain tumours, causing inevitable neurologic sequelae and premature death. A prior phase II study using the chemotherapy regimen of procarbazine, lomustine (also called CCNU) and vincristine showed a tumour regression benefit post radiation therapy, after a median follow-up time of 5.9 years. This study was a phase III trial using the same chemotherapy regimen above, but randomized to include radiation therapy or radiation therapy alone, in addition to long-term follow-up. In the radiation therapy and chemotherapy arm, progression-free survival and overall survival were longer compared to radiation therapy alone. This effect was greatest in patients with oligodendroglioma or oligoastrocytoma, and with patients having IDH1 R132H mutations. There were more instances of grade 1 and 2 toxicity in the combination therapy group (e.g. fatigue, nausea, vomiting, anorexia). There were no reports of any grade 5 toxicities in either of the treatment arms. Strengths of this study include randomized controlled trial methodology, and long-term follow-up not previously achieved in other studies. Limitations include the small patient numbers and single institution data. Favourable prognosticators for progression-free and overall survival included receiving radiation plus chemotherapy, and oligodendroglioma histology.
In-Depth [randomized controlled trial]: This phase III trial provided long-term survival data from grade 2 glioma patients receiving procarbazine, CCNU and vincristine, plus radiation therapy, versus radiation therapy alone. Patients included those having grade 2 astrocytoma, oligoastrocytoma or oligodendroglioma, who were younger than 40 years old and had subtotal resection or biopsy, or who were 40 years of age or older. These patients were randomly assigned to radiation therapy alone, or radiation therapy followed by 6 cycles of chemotherapy.
There were a total of 254 patients who underwent randomization between 1998 to 2002: 128 patients in the radiation therapy alone group, and 126 patients in the radiation therapy plus chemotherapy group. The median follow-up time was 11.9 years and at the time of analysis, 67% of enrolled patients had tumour progression, and 55% died. Patients receiving radiation therapy and chemotherapy had a longer progression-free survival (10.4 years; 95% [CI], 6.1 to not reached) compared to those receiving radiotherapy alone (4.0 years, 95% [CI], 3.1 to 5.5). The overall survival for radiation plus chemotherapy was significantly longer compared to radiation therapy alone (13.3 vs. 7.8 years; HR for death, 0.59; p=0.03).
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