Objectives: Acridine compounds are believed to exhibit anti-cancer cytotoxic effects because of interactions with both DNA and RNA. Pyrazoloacridine (PZA) (NSC No. 366140) is a 9-methoxyacridine compound that has demonstrated activity in some patients with solid tumors. The Gynecologic Oncology Group (GOG) performed a phase II trial of PZA to determine the response rate of this agent in patients with recurrent platinum-sensitive ovarian cancer.
Methods: Patients with recurrent ovarian cancer who experienced a progression-free interval of greater than 6 months after response to platinum-based chemotherapy are defined as platinum sensitive by the GOG and were eligible for this trial. PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 3 weeks.
Results: Among 42 evaluable patients, there was 1 (2.4%) complete response and 9 (21.5%) partial responses, including 1 patient who had a partial response after 10 courses of treatment. The major toxicity was neutropenia; severe thrombocytopenia was infrequent.
Conclusion: PZA demonstrates moderate activity in this chemotherapy-sensitive population, with manageable hematologic toxicity. Due to its unique mechanism of action and preclinical activity against hypoxic and noncycling cells, PZA should be considered for evaluation in combination with other active agents.