ATCT-32: A PHASE II STUDY OF TEMOZOLOMIDE IN THE TREATMENT OF ADULT PATIENTS WITH SUPRATENTORIAL LOW-GRADE GLIOMA

INTRODUCTION: Optimal adjuvant management of low-grade gliomas (LGGs) remains controversial. Radiotherapy has been shown to improve progression-free survival compared to observation, but carries the potential for substantial late toxicity. In an effort to delay or obviate the need for radiotherapy, there has been increasing interest in the use of adjuvant chemotherapy in LGGs. However, there is a dearth of prospective studies with long-term follow-up evaluating the efficacy of adjuvant chemotherapy without radiation in patients with newly diagnosed LGGs. METHODS: Patients over the age of 18 with histologically proven supratentorial LGG (WHO grade II) who underwent subtotal resection or biopsy were eligible for enrollment. All patients received monthly cycles of oral Temozolomide (TMZ) for 12 months or until disease progression. Patients were assessed for radiographic response and progression with MRIs every two months during and after treatment. The primary outcome was objective radiographic response rate; secondary outcomes included progression-free and overall survival. RESULTS: 120 patients were enrolled in the trial (57 oligodendrogliomas, 20 oligoastrocytomas, 43 astrocytomas), with a median follow-up of 6.9 years. Objective responses were seen in 7 patients (6%), and 86% demonstrated stable or improved disease during treatment with TMZ. Median progression-free survival was 4.2 years, and median overall survival was 9.7 years. Partitioning analysis demonstrated favorable results in patients with disease confined to one hemisphere undergoing subtotal resection. Treatment was well tolerated with minimal toxicity. CONCLUSIONS: In this high-risk cohort of newly diagnosed LGGs undergoing subtotal resection or biopsy, adjuvant TMZ alone achieved progression-free survival comparable to that seen in similar cohorts treated with adjuvant radiation. TMZ was very well tolerated, and could be considered as adjuvant therapy in appropriately selected patients. Work is ongoing to determine the demographic, pathologic and molecular characteristics of patients who are optimal candidates for adjuvant TMZ.