A comparative study of two different doses of cytarabine for acute myeloid leukemia: a phase III trial of Cancer and Leukemia Group B

Abstract

Between 1982 and 1986, 326 evaluable patients with acute myeloid leukemia (AML) were randomized to receive cytarabine (Ara-C) at 200 mg/m2 (A200) or 100 mg/m2 (A100) for induction and maintenance therapy. Cycle 1 of induction therapy consisted of 7 days of continuous intravenous (IV) Ara-C and 3 days of i.v. daunorubicin (DNR); cycle 2, if needed, consisted of 5 days of Ara-C and 2 days of DNR. Complete responders (CR) then received monthly subcutaneous (SC) Ara-C at the respective doses (A100 or A200) with 6-thioquanine (6TG) at months 1 and 5, with vincristine (VCR) and prednisone at months 2, 4, 6, and 8, and with DNR at months 3 and 7. Complete response rates were 58% (A100) and 64% (A200) (P = .29). Median survival was 46 weeks (A100) and 38 weeks (A200) (P = .64); 5-year survival was 10% (A200) and 8% (A100). Median time to remission was 6.7 weeks (A200) and 8.1 weeks (A100) (P = .18). Median disease-free survival was 41 weeks (A200) and 44 weeks (A100) (P = .86). Deaths were attributed to therapy-related toxicities in 21% (A200) and 13% (A100) (P = .05). The 5-year survival was 15% for patients with performance status (PS) 0, 8% for PS 1 to 2, and 2% for PS 3 to 4, 18% for patients less than 40 years, 8% for ages 40 to 59, and 3% for age 60 or greater. Stratification of data by age and PS suggested that A200 may improve survival in patients less than 60 years with a good PS 0 (P = .05). This trial does not support the superiority of A200 over A100 in the treatment of AML.

Finding chemo: the search for marine-based pharmaceutical drugs active against cancer

“…Similar toxicities were also observed in a phase III clinical trial at low dose (100 mg/m 2 ) and high dose (200 mg/m 2 ) of Cytosar-U. [111] This study was able to conclude that high-dose regimen used did not have a significant difference in overall survival or duration of relapse-free survival compared with the low-dose regimen. A similar study compared two induction regimens in 860 patients between the ages of 16 and 60 years.…”

A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia

“…Until recently, in most centres, the standard initial induction chemotherapy for patients younger than 60-65 years with newly diagnosed acute myeloid leukaemia (AML) consisted of 7 d of cytarabine at 100-200 mg/m 2 /d and 3 d of daunorubicin at 45-50 mg/m 2 /d, the so-called '7&3' regimen (Yates et al, 1982;Dillman et al, 1991). However, in an attempt to improve response rates, various approaches have been explored, predominantly the intensification of this standard regimen, including the use of alternative anthracyclines (Berman et al, 1991;Mandelli et al, 1991;Vogler et al, 1992;Wiernik et al, 1992), increased doses of daunorubicin (Fernandez et al, 2009;Lowenberg et al, 2009), addition of third drugs, such as etoposide (Bishop et al, 1990), and increasing the dose of cytarabine (Mayer et al, 1994;Bishop et al, 1996;Weick et al, 1996;Buchner et al, 1999;Estey et al, 2001).…”

Comparison of allogeneic stem cell transplantation, high‐dose cytarabine, and autologous peripheral stem cell transplantation as postremission treatment in patients with de novo acute myelogenous leukemia

“…Longer treatment with ara-C ("3ϩ10") does not induce higher remission rates, but the ''3ϩ7'' and ''3ϩ10'' regimens reportedly are more effective than less intensive regimens. [1][2][3][4] In recent years, three large randomized trials, including idarubicin in the induction regimen, produced significantly higher CR rates and prolonged survival compared with daunorubicin (55-60% and 69 -80%). [5][6][7] A metaanalysis of such studies suggested that idarubicin is associated with high CR rates and prolonged survival.…”