Phase II trial of pyrazoloacridine (NSC#366140) in patients with metastatic breast cancer.
OBJECTIVE
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).


METHODS
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.


RESULTS
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).


CONCLUSIONS
Pyrazoloacridine demonstrated modest activity in patients with metastatic breast cancer.
Division of Hematology and Oncology, Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH 43210, USA. Bhuvaneswari.Ramaswamy@osumc.edu
Bhuvaneswari
B
Ramaswamy
Ewa
E
Mrozek
John Philip
JP
Kuebler
Tanios
T
Bekaii-Saab
Eric H
EH
Kraut
D000166:Acridines / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003710:Demography; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000166:Acridines; D000970:Antineoplastic Agents; D011720:Pyrazoles; C064541:NSC 366140