Intra-arterial cisplatin plus oral etoposide for the treatment of recurrent malignant glioma: a phase II study.

Twenty-five adults with recurrent malignant glioma were enrolled into a phase II clinical study. All patients had undergone surgical resection and had failed radiotherapy and first-line treatment with nitrosourea-based chemotherapy; five had failed second-line chemotherapy. Our objective was to test the efficacy of combining intra-arterially (i.a.) infused cisplatin and oral etoposide. Using conventional angiographic technique to access anterior/posterior cerebral circulation, cisplatin 60 mg/m2 was administered by i.a. infusion on day 1 of treatment. Oral etoposide 50 mg/m2/day was given days 1-21, with a 7 day rest interval between courses. Response to treatment was evaluated in 20 patients. Two patients with anaplastic astrocytoma had partial responses (PR) and six patients experienced stable disease (SD) for an overall response rate (PR +/- SD) of 40%. The median time to disease progression (MTP) following treatment for the responder subgroup was 18 weeks. The median survival time from treatment (MST) for the responders (n = 8) and non-responders (n = 12) was 56.5 weeks and 11 weeks, respectively. Combined i.a. cisplatin and oral etoposide was well-tolerated, but produced an objective response in only a minority of patients. Those considered responders (PR + SD) experienced significant survival advantage when compared to the non-responders. Nonetheless, i.a. delivery of chemotherapy is an expensive and technologically burdensome treatment for most patients to access, requiring proximity to a major center with neuro-oncological and neuroradiological clinical services. This is of special concern for patients suffering recurrent disease with progressive neurological symptoms at a time in their course when quality of life must be safeguarded and palliation of symptoms should be the therapeutic goal. Despite the efforts of previous investigators to use this combination of agents to treat recurrent malignant glioma, we cannot recommend the use of i.a. chemotherapy for salvage treatment of this disease.