title: Single-agent laromustine, a novel alkylating agent, has significant activity in older patients with previously untreated poor-risk acute myeloid leukemia.
abstract: 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/m(2) 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.
authors.affiliation: Cancer Therapy and Research Center at The University of Texas Health Science Center, 7979 Wurzbach Rd, Mail Code 8026, Urschel Tower, Suite 600, San Antonio, TX 78229, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schiller
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Brien
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pigneux
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Deangelo
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kell
authors.forename: Scott
authors.initials: S
authors.lastname: Solomon
authors.forename: Robert K
authors.initials: RK
authors.lastname: Stuart
authors.forename: Verena
authors.initials: V
authors.lastname: Karsten
authors.forename: Ann L
authors.initials: AL
authors.lastname: Cahill
authors.forename: Maher X
authors.initials: MX
authors.lastname: Albitar
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015897:Comorbidity; D005060:Europe / Q000453:epidemiology; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006331:Heart Diseases / Q000401:mortality; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008107:Liver Diseases / Q000401:mortality; D008171:Lung Diseases / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D006834:Hydrazines; D013449:Sulfonamides; C483604:laromustine