Журнал канцерогенеза и мутагенеза

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Irinotecan and BCNU-Impregnated Wafers Used in Combination, for the Treatment of Patients with Recurrent Glioblastoma Multiforme

Sheri Dewan, Edward Stopa, Lloyd Alderson and Prakash Sampath

Introduction: This retrospective study examines the toxicity of the combination of intravenous irinotecan, (CPT-11; Camptosar®; Pharmacia & Upjohn, Kalamazoo, Mich.) and BCNU (1,3-bis(2-chloroethyl)-1-nitrosurea) impregnated wafers (Gliadel®) following implantation at the time of tumor recurrence in patients with glioblastoma multiforme (GBM). Method: Ten patients with recurrent GBM were examined in this study. The inclusion criteria were histologically confirmed GBM, Karnofsky’s Performance Scale (KPS) greater than or equal to 60, and a single focus of recurrent tumor. All patients underwent resection of their tumor at the time of first recurrence with placement of BCNU wafers. Postoperatively, patients were treated with irinotecan. One cycle constituted of 125 mg/m2 once weekly for 4 weeks followed by a 2-week rest. The patients were followed for toxicity, tumor progression and survival. Treatment was discontinued if intolerable side effects ensued. Results: The mean time to tumor progression was 4.35 months. The mean survival from the time of BCNU wafer placement was 12.1 months. The overall mean survival was 18.9 months. The average number of cycles of CPT-11 that patients received was 2.7. The toxicity associated with the CPT-11 was as follows: two patients reported Grade 2 diarrhea and one patient experienced grade 3 pancytopenia, three patients reported deep vein thromboses and one patient suffered a non-life threatening pulmonary embolism. Conclusions: The combination of systemic irinotecan along with local intratumoral BCNU is well tolerated and may be more efficacious than either treatment alone. Our data support the need for a future prospective study designed to confirm the effectiveness of this combined treatment strategy.