Summary
PCNU the latest nitrosourea analogue to be subjected to clinical trials, held promise as a superior chemotherapy agent for brain tumors because of more favorable biochemical and cytotoxic characteristics in laboratory studies. Thirty-nine children with a variety of recurrent primary CNS tumors, all of whom had evaluable disease, participated in a phase 11 PCNU trial. Their mean age was 9.7 (3–20) years. PCNU was administered as a 2 hour intravenous infusion in one of 2 dose schedules at 6–7 week intervals; 100–125 mg/m2 for minimally treated patients and 70–90 mg/m2 for heavily treated patients. Response was assessed after 2 courses of chemotherapy after attempting to taper the steroid dose. The overall objective response rate was 18% (7/39) for a mean of 5.9 months (2+−12). Only partial responses were observed. Disease-specific responses rates were: brainstem glioma - 18% (3/17); cerebral glioma - 27% (3/12); ependymoma- 1/1; and primitive neuroectodermal tumors - (0/9) including 5 medulloblastomas, 2 pineoblastomas and 3 cerebral primitive neuroectodermal tumors. Toxicity was primarily hematologic and clinically significant thrombocytopenia (< 50000 mm3) was encountered in 30/38 (79%) patient trials. Modest activity of PCNU in recurrent childhood gliomas is confirmed. Our response rates, using objective CT criteria, are somewhat lower than those reported for BCNU and CCNU. Because of comparable hematologic toxicity and efficacy, intravenous PCNU does not appear to offer a clinical advantage to existing nitrosoureas for children with recurrent brain tumors using a 2 hour intravenous infusion schedule.
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Allen, J.C., Hancock, C., Walker, R. et al. PCNU and recurrent childhood brain tumors. J Neuro-Oncol 5, 241–244 (1987). https://doi.org/10.1007/BF00151228
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DOI: https://doi.org/10.1007/BF00151228