PCNU and recurrent childhood brain tumors

Abstract

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 II 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 (less than 50,000 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.

Radiotherapy followed by high dose busulfan and thiotepa

“…[27][28][29][30] Occasional responses have been reported with PCNU, cyclophosphamide, and etoposide. [31][32][33] When chemotherapy is added to radiotherapy, there is no evidence that it influences survival rate or duration. The Children's Cancer Study Group conducted a randomized study, but this was during the early CT scan era with less rigorous selection criteria.…”

The Present State of Antineoplaston Research (1)

“…In a phase II PCNU trial, 18% of patients obtained PR and 12% obtained SD, compared to the total of 80% of CR, PR, and MR in our study (Figure 6). 63 In the study with thiotepa, in 14 cases there were no objective responses. 64 A paper by Mandell et al analyzes the results of 66 patients treated with radiation therapy and chemotherapy with cisplatin.…”

Chemotherapy in Recurrent Ependymoma

“…PCNU (70-90 mg/ m 2 /dose), a nitrosourea analogue, was utilized in a phase II trial in recurrent brain tumors. The only patients with ependymoma had a PR [12]. The low response rates observed with these agents (3/10) probably explain, at least partially, the failure of the randomized CCG protocol utilizing CCNU.…”