Phase II trial of pyrazoloacridine in children with solid tumors: A Pediatric Oncology Group phase II study

Purpose: Pyrazoloacridine (PZA), a rationally synthesized deoxyribonucleic acid (DNA) binding agent that preferentially inhibits ribonucleic acid rather than DNA synthesis, is active against hypoxic and noncycling tumor cells and has greater in vitro activity against a broad range of human solid tumor lines than against the L1210 murine leukemia line. The Pediatric Oncology Group conducted a phase II study to determine the activity of PZA administered as a 3-hour infusion. Patients and Methods: The activity of PZA was evaluated in patients with a variety of childhood solid tumors including rhabdomyosarcoma, Ewing sarcoma/peripheral neuroectodermal tumor, neuroblastoma, osteogenic sarcoma, Wilms tumor, or other solid tumors (excluding brain tumors). In addition to a standard three-stage design to test the drug's activity in each tumor type, a global stopping rule was used such that if no complete or partial responses (CR or PR) occurred in the first 35 patients (pooled across all strata except "other"), the study would be closed. Results: A total of 47 patients were entered into the study. Myelosuppression was the primary toxicity. Severe nonhematologic toxicity was uncommon. Only one patient exhibited grade 3 neurologic toxicity (anxiety). No CRs or PRs were observed. Conclusion: Use of the global stopping criterion permitted early identification of lack of activity of PZA against childhood solid tumors.