Treatment > Pyrazoloacridine

Meeting Abstract

A phase I/II trial of pyrazoloacridine (PZA) in adults with newly diagnosed glioblastoma multiforme (GBM)

Glenn J Lesser, Kit Carson, Regina Priet, L. B Nabors, Thomas Doyle, Stuart A Grossman

The New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium, Baltimore, MD

PZA is a synthetic acridine derivative with broad spectrum preclinical antitumor efficacy thought to be related to topoisomerase I and II inhibition. 
In preclinical in vivo systems, PZA displays unique properties including solid tumor selectivity and activity against hypoxic and noncycling cells. 
The NABTT CNS consortium is conducting a Phase I/II trial of pre-irradiation PZA in patients with newly diagnosed GBM with measurable disease on postoperative contrast-enhanced brain MRI scans. 
In light of prior NABTT experience with unexpected drug interactions in brain tumor patients, concurrent dose escalations are underway in patients receiving hepatic enzyme-inducing anticonvulsant drugs (EIAD) and in patients not receiving those drugs. 
The starting dose of PZA in both arms was 750mg/m2 given as a 3 hour intravenous infusion. 
Eligible patients can receive up to 4 cycles of PZA, given at 3 week intervals, prior to receiving standard radiation therapy. 
Dose escalations were determined by the CRM method and 3 patients were treated at each dose level. 
To date, 8 patients (4 female) have been enrolled in this trial, 6 on the +EIAD arm. 
A total of 15 cycles of PZA have been delivered and pharmacokinetic sampling has been performed in all enrolled patients. 
Dose escalation to 871 mg/m2 and 1082 mg/m2 has been accomplished in the +EIAD arm. 
The observed drug-related toxicity has been minimal thus far and limited to 2 episodes of grade 3/4 neutropenia. 
No grade 3/4 drug-related neurotoxicity has been observed to date. 
Only 1 patient has received all 4 planned pre-irradiation cycles of PZA. 
Administration of PZA appears to be safe and not accompanied by excessive neurotoxicity in patients with malignant brain tumors. 
Response, toxicity and pharmacokinetic information will continue to be collected as additional patients are enrolled on this trial.

© Copyright 2002 American Society of Clinical Oncology