nsc-366140 and Neoplasm-Metastasis

Pyrazoloacridine (PZA) is an investigational nucleic acid binding agent that inhibits the activity of topoisomerases 1 and 2. We conducted a phase II clinical study to determine the efficacy and toxicities of PZA in patients with metastatic breast cancer (MBC).. In this phase II multicenter study, patients who were treated with no more than one prior chemotherapy for MBC were treated with 750 mg/m² of PZA given as a 3-hour intravenous infusion every 3 weeks. Treatment cycles were continued until disease progression or unacceptable toxicities. The study was designed to distinguish between a response rate of < 15% vs > 30% (alpha = 0.10, beta = 0.10) using Simons optimal 2-stage design. At least 2 responses were required in the first 12 patients in the 1st stage and 6 of 35 in the 2nd stage to recommend the agent for further study.. Two patients in the first stage had a response allowing accrual to second stage. A total of 15 patients (out of 35 planned) were treated on the study prior to premature closure. Three patients had a partial response (20%) lasting 4.5-6 months. Two patients had stable disease for 3 and 5 months. The dose limiting toxicity was granulocytopenia with ten patients requiring dose reduction or dose delay for grade 4 neutropenia. Other grade 3 and 4 toxicities include vomiting (n = 2), nausea (n = 2), neurotoxicity (n = 1), fatigue (n = 1), anemia (n = 1), dyspnea 9n = 1) and renal (n = 1).. Pyrazoloacridine demonstrated modest activity in patients with metastatic breast cancer.

Topics: Acridines; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Demography; Female; Humans; Middle Aged; Neoplasm Metastasis; Pyrazoles; Treatment Outcome

To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy.. 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.. 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).. PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity.

Topics: Acridines; Adult; Aged; Antineoplastic Agents; Colonic Neoplasms; Female; Humans; Intercalating Agents; Male; Middle Aged; Neoplasm Metastasis; Nervous System Diseases; Neutropenia; Pyrazoles; Rectal Neoplasms