A phase II pharmacodynamic study of pyrazoloacridine in patients with metastatic colorectal cancer

Purpose: To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no prev ious therapy. Methods: PZA was administered at a dose of 750 mg/m(2) intrav enously over 3 h every 21 days. Pharmacokinetic studies to determine PZA pl asma concentrations were performed. Results: No responses were seen in 14 r esponse-evaluable patients. Patients received a median of two cycles of PZA (range 1-6). Toxicity included neutropenia and neurologic side-effects, wh ich were greater than or equal to grade III in 73% and 14%, respectively. H igh plasma concentrations of PZA (C-max) correlated with low neutrophil cou nts (P = 0.04). Conclusions: PZA is inactive at this dose and schedule in c olorectal cancer, and produces moderately severe toxicity.