TY - JOUR
T1 - Phase II trial of pyrazoloacridine (NSC#366140) in patients with metastatic breast cancer
AU - Ramaswamy, Bhuvaneswari
AU - Mrozek, Ewa
AU - Kuebler, John Philip
AU - Bekaii-Saab, Tanios
AU - Kraut, Eric H.
N1 - Funding Information:
Funding NCI grant # U01 63185 P30 CA 16058 B.Ramaswamy(*).E.Mrozek.T.Bekaii-Saab.E.H.Kraut 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 e-mail: Bhuvaneswari.Ramaswamy@osumc.edu
PY - 2011/4
Y1 - 2011/4
N2 - Purpose: 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). Experimental Design: 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.
AB - Purpose: 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). Experimental Design: 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.
KW - Metastatic breast cancer
KW - Phase II
KW - Pyrazoloacridine
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U2 - 10.1007/s10637-009-9338-1
DO - 10.1007/s10637-009-9338-1
M3 - Article
C2 - 19844661
AN - SCOPUS:79957464991
SN - 0167-6997
VL - 29
SP - 347
EP - 351
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 2
ER -