PHASE-II STUDY OF PYRAZOLOACRIDINE IN PATIENTS WITH ADVANCED COLORECTAL-CARCINOMA

Purpose: Pyrazoloacridine (PZA) is an acridine derivative selected for clinical development because of broad preclinical antitumor activity and solid tumor selectivity. Phase I evaluations with PZA have demonst rated predictable toxicity and suggested clinical efficacy. A phase II trial in patients with previously untreated advanced colorectal cance r was conducted. Methods: PZA was administered at a dose of 750 mg/m(2 ) intravenously over 3 h every 21 days to patients who received a tota l of 31 courses of PZA. Results: In 15 patients evaluable for response , no responses were observed (0% response rate, 95% confidence interva l 0-22%). Toxicity to PZA consisted of myelosuppression and neurotoxic ity that was treatment-limiting in several instances. Conclusion: PZA at this dose and schedule of administration is inactive in patients wi th colorectal cancer.