Toxicities related to intraarterial infusion of cisplatin and etoposide inpatients with brain tumors

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 duri ng the first passage of the drugs through tumor capillaries. Initial IAC tr ials had less than satisfactory results due to unacceptable toxicities. Bet ween 1987 and 1996, 173 patients with primary and metastatic brain tumors w ere treated with intraarterial (intracarotid and/or intravertebral) cisplat in and etoposide (VP-16). Out of these, 168 patients, who received a total of 438 cycles, were evaluated for the incidence of toxicities. Patients rec eived either cisplatin at 40 mg/m(2) and VP-16 at 20 mg/m(2) or cisplatin a t 60 mg/m(2) and VP-16 at 40 mg/m(2). Nausea and vomiting were the most com mon toxicities (42 patients, 14% of cycles). Arterial puncture was associat ed with a 1.6% incidence of groin hematomas (6 patients), and a 0.7% incide nce 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 ret ention/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 high er in patients with metastatic brain tumors than in those with primary brai n tumors (34% versus 17%, p < 0.001). It was also higher in patients who ha d brain radiation therapy (RT) prior to IAC than in those who had RT concom itant with IAC (31% versus 19%, p = 0.05). No significant difference in tox icity incidence was noticed between patients who received RT concomitant wi th 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 ch emotherapy with cisplatin and VP-16 is a relatively safe treatment modality , especially in patients with primary brain tumors who have not received br ain radiotherapy.