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Published on: March 14, 2019
A phase II pharmacodynamic study of pyrazoloacridine in patients with metastatic colorectal cancer
R Pelley1, R Ganapathi, L Wood
1Experimental Therapeutics Program, The Cleveland Clinic Cancer Center, OH 44195, USA.
Purpose:
To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy.
Methods:
PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed.
Results:
No responses were seen in 14 response-evaluable patients. Patients received a median of two cycles of PZA (range 1-6). Toxicity included neutropenia and neurologic side-effects, which were > or = grade III in 73% and 14%, respectively. High plasma concentrations of PZA (Cmax) correlated with low neutrophil counts (P = 0.04).
Conclusions:
PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity.
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