Salvage chemotherapy with CPT-11 for recurrent temozolomide-refractory anaplastic astrocytoma

BACKGROUND. The primary objective of this prospective phase 2 study of CPT-11 in adult patients with recurrent temozolomide-refractory anaplastic astrocytoma (AA) was to evaluate 6-month progression-free survival (PFS). METHODS. Forty patients (27 men and 13 women) ages 17 to 58 years (median age, 38 years) with radiographically recurrent AA were treated. All patients had been treated previously with surgery, involved-field radiotherapy, and adjuvant chemotherapy. Fifteen patients were treated at first recurrence with an alternative chemotherapy. All patients were treated at either first or second recurrence with CPT-11 administered intravenously once every 3 weeks, which was defined operationally as a single cycle. Neurologic and neuroradiographic evaluations were performed every 9 weeks. RESULTS. All patients were evaluable for toxicity, and 39 patients were evaluable for response. In total, 302 cycles of CPT-11 (median, 6 cycles; range, 1-22 cycles) were administered. CPT-11-related toxicity included diarrhea (19 cycles), leukopenia (16 cycles), fatigue (11 cycles), anemia (6 cycles), delayed nausea/vomiting (5 cycles), neutropenia (5 cycles), and renal failure (1 patient, 1 toxic death). Two patients (5%) patients required erythrocyte transfusions. Nine patients (23%) demonstrated a radiographic complete response (1 patient) or partial response (8 patients), 16 patients (41%) demonstrated stable disease, and 14 patients (36%) had progressive disease after 3 cycles of CPT-11. The median time to tumor progression was 4.1 month. The median survival was 6.9 months, and the 6-month and 12-month PFS rates were 40% and 5%, respectively. CONCLUSIONS. CPT-11 demonstrated modest efficacy with acceptable toxicity in this cohort of adult patients with recurrent AA, all of whom had failed on prior temozolomide chemotherapy.