Salvage chemotherapy with CPT-11 for recurrent meningioma

Background: A prospective Phase II study of irinotecan (CPT-11) in adult patients with recurrent surgery and radiotherapy-refractory WHO Grade I meningioma. Methods: Sixteen patients (5 men; 11 women) ages 48-70 years (median 62.5), with recurrent meningioma were treated. All patients had previously been treated with surgery (complete in 4; partial in 9; biopsy in 3) and involved-field radiotherapy (median dose 54 Gy; 12 following first surgery and 4 following second surgery). Additionally, eight patients underwent re-operation (complete in 2; partial in 6) and eight patients were treated with salvage stereotactic radiosurgery. No patient was treated with prior chemotherapy. CPT-11 was administered intravenously every 3 weeks (350 mg/m(2)/day in patients on non-enzyme inducing anticonvulsants [NEIAED]; 600 mg/m(2)/day in patients on enzyme-inducing anticonvulsants [EIAED]) for 9 weeks (operationally defined as a single cycle). Neurological and neuroradiographic evaluation were performed every 10 weeks. Results: All patients were evaluable. A median of two cycles of CPT-11 (range 1-4) was administered. CPT-11 related-toxicity (>= grade 3) included diarrhea (6 occurrences, 19% all cycles administered), granulocytopenia (6, 19%), leukopenia (5, 16%), thrombocytopenia (3, 10%) and anemia (3, 10%). Four patients required transfusion (3 RBC and 1 platelet). One patient developed neutropenic fever without bacteriologic confirmation. No treatment-related deaths occurred. No patient demonstrated a neuroradiographic complete or partial response (PR), 13 patients (81%) demonstrated stable disease but disease progressed after 2 cycles of CPT-11, and 3 patients (19%) had progressive disease (PD) following a single cycle of CPT-11. Time to tumor progression ranged from 2.5 to 5.0 months (median 5.0 months). Survival ranged from 4 to months (median 7.5 months). Conclusions: The primary objective was to estimate the 6-month progression-free survival (PFS) after study entry. As no patient demonstrated PFS at 6-months, the study was stopped prematurely as specified by study design. Using CPT-11 in this moderately toxic dose schedule failed to demonstrate efficacy in this cohort of adult patients with recurrent surgery and radiotherapy-refractory meningioma.