Toxicities related to intraarterial infusion of cisplatin and etoposide in patients with brain tumors.

Abstract

Chemotherapy for malignant brain tumors has a limited efficacy largely due to restricted blood-brain barrier permeability for chemotherapeutic drugs. Intraarterial chemotherapy (IAC) has the advantage of increased uptake during the first passage of the drugs through tumor capillaries. Initial IAC trials had less than satisfactory results due to unacceptable toxicities. Between 1987 and 1996, 173 patients with primary and metastatic brain tumors were treated with intraarterial (intracarotid and/or intravertebral) cisplatin and etoposide (VP-16). Out of these, 168 patients, who received a total of 438 cycles, were evaluated for the incidence of toxicities. Patients received either cisplatin at 40 mg/m2 and VP-16 at 20 mg/m2 or cisplatin at 60 mg/m2 and VP-16 at 40 mg/m2. Nausea and vomiting were the most common toxicities (42 patients, 14% of cycles). Arterial puncture was associated with a 1.6% incidence of groin hematomas (6 patients), and a 0.7% incidence of failure to canulate the carotid or vertebral arteries (3 patients). Neurologic toxicities included headache (1.4% of cycles, 5 patients), focal seizures (1.4% of cycles, 5 patients), transient confusion and urinary retention/incontinence (1.9% of cycles, 8 patients), and blurred vision (0.9% of cycles, 4 patients). We have not seen visual loss, strokes, major vessel dissection or thrombosis, or myelosuppression. Toxicity incidence was higher in patients with metastatic brain tumors than in those with primary brain tumors (34% versus 17%, p < 0.001). It was also higher in patients who had brain radiation therapy (RT) prior to IAC than in those who had RT concomitant with IAC (31% versus 19%, p = 0.05). No significant difference in toxicity incidence was noticed between patients who received RT concomitant with IAC and those who received RT after IAC (19% and 23% respectively, p = 0.08). Intracarotid chemotherapy given prior to RT resulted in 23 months of median survival for patients with glioblastoma multiforme. Intraarterial chemotherapy with cisplatin and VP-16 is a relatively safe treatment modality, especially in patients with primary brain tumors who have not received brain radiotherapy.