A phase I study of the intracarotid administration of
PCNU was conducted in patients with intracerebral
tumors recurring after cranial radiation. Seventeen patients were treated including 16 with recurrent
gliomas or
glioblastomas and 1 with recurrent
brain metastases from
adenocarcinoma of the lung. An additional patient received a vertebral artery infusion of
PCNU for a recurrent
glioblastoma. Seven of 17 patients receiving intracarotid
PCNU responded for a response rate of 41%. If only evaluable patients with
gliomas are considered, the response rate was 44%.
Tumor grade at time of initial diagnosis, exposure to prior
chemotherapy, and dose of
PCNU did not appear to have a major impact on response rate. Zubrod performance status 3 patients had a lower response rate (25%) than did patients with performance status 1 or 2 (response rate 63%).
Thrombocytopenia and reversible central nervous system toxicity were dose limiting at a
PCNU dose of 110 mg/m2. Two patients had possible permanent central nervous system toxicity. Three patients had permanent ipsilateral
visual impairment, including one at the lowest dose used into the carotid artery (60 mg/m2). Orbital
pain appeared to be substantially less than that seen with intracarotid
BCNU but
headaches may have been somewhat more common. The single patient receiving a vertebral artery infusion developed marked
headaches and
restlessness after receiving 25 mg/m2 of a planned 75 mg/m2 treatment into the vertebral artery and the treatment had to be discontinued. Symptoms were rapidly reversible upon stopping the medication. Our overall impression is that intracarotid
PCNU causes less ocular
pain but more transient central nervous system toxicity than does intracarotid
BCNU.(ABSTRACT TRUNCATED AT 250 WORDS)