Phase I study of intracarotid PCNU.
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)
Stewart
D J
DJ
Ontario Cancer Treatment and Research Foundation, Ottawa Regional Cancer Centre, Canada.
Grahovac
Z
Z
Russel
N A
NA
Hugenholtz
H
H
Gupta
S
S
Benoit
B C
BC
Richard
M T
MT
Maroun
J A
JA
Hopkins
H S
HS
Locke
L
L
D000328:Adult; D000368:Aged; D000477:Alkylating Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002343:Carotid Artery, Internal; D004341:Drug Evaluation; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C018627:1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidinyl)-1-nitrosourea