“Eight-drugs-in-one-day” chemotherapy administered before and after radiotherapy to adult patients with malignant gliomas

Abstract

Thirty‐one adult patients with malignant glioma (23 with glioblastoma multiforme, six with anaplastic astrocytoma, and two with brainstem glioma) were treated with up to ten cycles of “eight‐drugs‐in‐one‐day” chemotherapy (methylprednisolone 300 mg/m², vincristine 1.5 mg/m² [maximum of 2 mg/cycle], CCNU 75 mg/m², procarbazine 75 mg/m², hydroxyurea 3000 mg/m², cisplatin 90 mg/m², cytosine arabinoside 300 mg/m², and imidazole carboxamide 150 mg/m²). Chemotherapy was planned as two cycles before and eight cycles after 60 Gy of involved brain irradiation. A total of 117 cycles of chemotherapy was administered. There was one treatment‐related death. Myelosuppression was the most frequent toxic effect (leucopenia was < 1000/mm3 in 9% of cycles and 1000–2500/mm3 in 25%; thrombocytopenia was < 100,000/mm³ in 33% of cycles). Sixteen patients developed infections requiring treatment, two of which were life‐threatening. Five patients suffered ototoxicity. Nausea and vomiting were observed in 35% of patients. A reversible rise in creatinine was observed in five patients. One patient developed a severe motor neuropathy, and three patients developed mild peripheral neuropathies. Three patients had episodes of atrial fibrillation. One new bundle branch block with supraventricular tachycardia was observed in a patient with pulmonary embolus. Five patients developed thrombophlebitis, three of whom had pulmonary emboli. Two patients suffered strokes in areas anatomically separate from their tumor. Eleven patients declined to continue therapy after receiving an average of three cycles. Two had complete, and five had partial responses. The median survival time was 47 weeks. The responses and survival times observed are comparable to less toxic treatment protocols for adults with malignant gliomas.