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.

Increased remissions from one course for intermediate‐dose cytosine arabinoside and idarubicin in elderly acute myeloid leukaemia when combined with cladribine. A randomized population‐based phase II study

“…However, overall the protocol provided long-term survival seemingly superior to other studies in elderly AML patients. One-third of our patients survived 2-3 years, whereas this figure typically is <20% (Dillman et al, 1991;Mayer et al, 1994;Lowenberg et al, 1997;Amadori et al, 2001;Goldstone et al, 2001;Stone et al, 2001;Anderson et al, 2002;Baer et al, 2002) in studies with a high degree of patient selection, as well as for our non-protocol patients. A major prerequisite for our positive study result is likely to be the low early death rate of 11% (intention-to-treat analysis), in comparison with 20-54% in several published studies (Mayer et al, 1994;Hiddemann et al, 1999;Goldstone et al, 2001;Anderson et al, 2002;Baer et al, 2002;Wrzesien-Kus et al, 2002).…”

ACUTE MYELOID LEUKEMIA: TREATMENT OVER 60

“…It has been suggested that neutropenia after chemotherapy lasts longer in older patients (15) and that a defective pool of hematopoietic stem cells could prolong myelosuppression (16). The age‐related differences in the disease biology explain in part why patients 60 years of age and older do not achieve the same remission rates (17–27) and remission duration (20, 23, 25–27) as younger patients. On the other hand, inadequate antileukemic treatment might also have contributed to the inferior results as chemotherapy intensity has commonly been reduced in older patients.…”

“…The age‐related study results are listed in Table 1 in the order of increasing age in the groups of patients treated (16–27, 30–40, 43–48). If age specific therapeutic results were reported, the related publications were listed for separate age groups.…”

Current therapeutic strategies for acute myeloid leukaemia

“…Results using an anthracycline combined with a 7 d c.i.v. infusion of either 100 or 200 mg/m 2 daily of Ara‐C are comparable (Dillman et al , 1991). Extending the Ara‐C infusion to 10 d showed no advantage over 7 d (Preisler et al , 1987).…”