TY - JOUR
T1 - Single-agent laromustine, a novel alkylating agent, has significant activity in older patients with previously untreated poor-risk acute myeloid leukemia
AU - Schiller, Gary J.
AU - O'Brien, Susan M.
AU - Pigneux, Arnaud
AU - DeAngelo, Daniel J.
AU - Vey, Norbert
AU - Kell, Jonathan
AU - Solomon, Scott
AU - Stuart, Robert K.
AU - Karsten, Verena
AU - Cahill, Ann L.
AU - Albitar, Maher X.
AU - Giles, Francis J.
PY - 2010/2/10
Y1 - 2010/2/10
N2 - Purpose: An international phase II study of laromustine (VNP40101M), a sulfonylhydrazine alkylating agent, was conducted in patients age 60 years or older with previously untreated poor-risk acute myeloid leukemia (AML). Patients and Methods: Laromustine 600 mg/m2 was administered as a single 60-minute intravenous infusion. Patients were age 70 years or older or 60 years or older with at least one additional risk factor - unfavorable AML karyotype, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2, and/or cardiac, pulmonary, or hepatic comorbidities. Results: Eighty-five patients (median age, 72 years; range, 60 to 87 years) were treated. Poor-risk features included age 70 years or older, 78%; adverse karyotype, 47%; PS of 2, 41%; pulmonary disease, 77%; cardiac disease, 73%; and hepatic disease, 3%. Ninety-six percent of patients had at least two risk factors, and 39% had at least four risk factors. The overall response rate (ORR) was 32%, with 20 patients (23%) achieving complete response (CR) and seven (8%) achieving CR with incomplete platelet recovery (CRp). ORR was 20% in patients with adverse cytogenetics; 32% in those age 70 years or older; 32% in those with PS of 2; 32% in patients with baseline pulmonary dysfunction; 34% in patients with baseline cardiac dysfunction; and 27% in 33 patients with at least four risk factors. Twelve (14%) patients died within 30 days of receiving laromustine therapy. Median overall survival was 3.2 months, with a 1-year survival of 21%; the median duration of survival for those who achieved CR/CRp was 12.4 months, with a 1-year survival of 52%. Conclusion: Laromustine has significant single-agent activity in elderly patients with poor-risk AML. Adverse events are predominantly myelosuppressive or respiratory. Response rates are consistent across a spectrum of poor-risk features.
AB - Purpose: An international phase II study of laromustine (VNP40101M), a sulfonylhydrazine alkylating agent, was conducted in patients age 60 years or older with previously untreated poor-risk acute myeloid leukemia (AML). Patients and Methods: Laromustine 600 mg/m2 was administered as a single 60-minute intravenous infusion. Patients were age 70 years or older or 60 years or older with at least one additional risk factor - unfavorable AML karyotype, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2, and/or cardiac, pulmonary, or hepatic comorbidities. Results: Eighty-five patients (median age, 72 years; range, 60 to 87 years) were treated. Poor-risk features included age 70 years or older, 78%; adverse karyotype, 47%; PS of 2, 41%; pulmonary disease, 77%; cardiac disease, 73%; and hepatic disease, 3%. Ninety-six percent of patients had at least two risk factors, and 39% had at least four risk factors. The overall response rate (ORR) was 32%, with 20 patients (23%) achieving complete response (CR) and seven (8%) achieving CR with incomplete platelet recovery (CRp). ORR was 20% in patients with adverse cytogenetics; 32% in those age 70 years or older; 32% in those with PS of 2; 32% in patients with baseline pulmonary dysfunction; 34% in patients with baseline cardiac dysfunction; and 27% in 33 patients with at least four risk factors. Twelve (14%) patients died within 30 days of receiving laromustine therapy. Median overall survival was 3.2 months, with a 1-year survival of 21%; the median duration of survival for those who achieved CR/CRp was 12.4 months, with a 1-year survival of 52%. Conclusion: Laromustine has significant single-agent activity in elderly patients with poor-risk AML. Adverse events are predominantly myelosuppressive or respiratory. Response rates are consistent across a spectrum of poor-risk features.
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U2 - 10.1200/JCO.2009.24.2008
DO - 10.1200/JCO.2009.24.2008
M3 - Article
C2 - 20026800
AN - SCOPUS:77649194028
SN - 0732-183X
VL - 28
SP - 815
EP - 821
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 5
ER -