Treatment > Carmustine · Chemoresistance · Procarbazine

Meeting Abstract

Increased pulmonary toxicity with scheduling procarbazine prior to BCNU in patients with high-grade gliomas

Slancar M., Wheeler H., Cook R., Levi J., Bell D., Beith J.

Department of Oncology and Department of Neurosurgery, Royal North Shore Hospital, Sydney, Australia

Chloroethylnitrosoureas (CNUs) are the most active agent used to treat gliomas but the DNA repair protein, O⁶-methylguanine methyltransferase (MGMT), has been shown to be a major mechanism of resistance in vitro. 
We performed a study in 22 patients with relapsed high grade gliomas scheduling procarbazine 200 mg/m ² days 1-5, BCNU 80 mg/m² days 3-5 and vincristine 1.4 mg/m ² day 3 in an attempt to modulate this resistance.
Our hypothesis was that the procarbazine prior to BCNU would deplete MGMT levels and enhance the cytotoxicity of BCNU.
Response rates were increased compared to routine administration of these agents but a significant increase in pulmonary toxicity was observed.
Four out of 22 patients (18%) developed WHO grade 4 pulmonary toxicity after cumulative doses of BCNU at much lower levels than has been previously reported.
All patients had an improvement in respiratory function after cessation of protocol and commencement of corticosteroids.
There was a significant decrease in MGMT levels in peripheral blood monocytes (PBM) after 2 days treatment of procarbazine to a mean of 54% of pretreatment levels of all patients (P<0.001). 

We postulate that a similar depletion might in pulmonary parenchyma tissue lead to the increased pulmonary toxicity it does however increase the response in the treatment of relapsed high grade gliomas.

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