Phase I clinical trial of intracarotid bis-chloroethylnitrosourea (BCNU) and 2' dioxy-5-fluorouridine (FUDR) in malignant astrocytomas.

Systemic chemotherapy has been of limited benefit in the treatment of intracranial neoplasms, due, in part, to the inability to deliver effective drug doses to the neoplasm without systemic toxicity. We have completed a clinical trial of intracarotid BCNU and FUDR using an implantable pump in patients with unilateral malignant astrocytomas (Grade III and IV) in the hope of obtaining better tumor control with less systemic toxicity. Six patients had in-dwelling catheters placed in the internal carotid artery attached to a percutaneous refillable pump (Infusaid 400). The treatment program consisted of bolus BCNU 400 mg every 6 weeks and FUDR by continuous infusion at dosages ranging from 0.5 mg/24 h to 2.5 mg/24 h. The maximum tolerable dose of FUDR was 1 mg/24 h with ipsilateral mucositis and conjunctivitis being dose limiting factors. Flow studies demonstrated significant perfusion of the ipsilateral eye and surrounding face secondary to ophthalmic artery collaterals. No patient had systemic toxicity and the lowest WBC encountered was 2 400 with normal differential and platelets.