Neurotoxicity of combination chemotherapy with procarbazine, CCNU and vincristine (PCV) for recurrent glioma

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Abstract
In cerebral glioma combination chemotherapy with procabazine, CCNU and vincristine (PCV) is used as adjuvant therapy in cases of recurrence. Standard PCV is usually well tolerated, but intensive PCV (CCNU 130 mg/m2 on day 1, procarbazine 75 mg/m2 on day 8–21, vincristine 1.4 mg/m2 on day 8 and 29; 6 courses every 6 weeks) is less well tolerated. We observed central neurotoxic side effects (focal neurological deficit, cognitive disturbances, slowing of EEG background activity, atrophy on cerebral MR) in combination with hematological and hepatic toxicity in four of 26 PCV treated patients with recurrent glioma. Prolonged myelosuppression and/or ongoing (partial reversible in two patients) neurological deficit still influence daily life in three of four patients months after discontinuation of chemotherapy. Despite the fact that all four patients used anticonvulsants and have been treated with radiotherapy in the past, we have the strong impression that central neurotoxic side effects are related to intensive PCV therapy. We advocate to use the standard PCV regimen in patients with recurrent glioma, because of this potential toxicity and the lack of evidence that intensive PCV leads to better tumor control than standard PCV in cerebral glioma.