-transparent.png){kind=logo}
Sixty-four patients with refractory acute leukemia were treated with high-dose cytosine arabinoside given at a dosage of 3 g/m2 intravenously over two hours every 12 hours for four to 12 doses, repeated at two- to three-week intervals. Complete remissions were observed in 16 patients (25 percent), and the median duration of remission was three months (range, one to 10 months). Remission rates were similar for patients with acute myelogenous and acute lymphocytic leukemia (24 and 27 percent, respectively). Response rates were significantly higher in patients with initial remission durations of more than six months than in those with shorter remissions or those in whom there was no response to front-line therapy (41 and 9 percent; p less than 0.01). Similarly, patients with disease sensitive to conventional cytosine arabinoside had higher response rates than did those with resistant disease (54 and 17 percent; p = 0.03). Serial in vivo measurements of intracellular concentrations of the active metabolite of cytosine arabinoside in peripheral blasts following the initial dose demonstrated considerable individual variation. Favorable intracellular pharmacology of this active metabolite, manifested by its higher intracellular concentrations 12 hours after the first dose, by longer half-lives of active metabolite levels, and by higher values of the measured area under the curve of its accumulation and retention, was associated with higher response rates. Central nervous system toxicity occurred in 24 percent of patients, and pulmonary toxicity occurred in 22 percent; both were dose-limiting and dose-related. Other toxicities included nausea, vomiting, diarrhea, conjunctivitis, photophobia, cytosine arabinoside fever, skin rashes, and hepatic dysfunction. Response rates were similar for schedules utilizing four to six doses at two-week intervals or nine doses at three-week intervals (27 percent versus 25 percent). The schedule of 12 doses had a more rapid antileukemic effect but resulted in significantly higher toxicity and mortality rates during therapy with a similar overall response rate (21 percent). Thus, high-dose cytosine arabinoside is an effective regimen with substantial toxicity in patients with acute leukemia.
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
June 1986,
Onkologie,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
January 1987,
Haematology and blood transfusion,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
August 1983,
Blood,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
September 1984,
Blood,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
October 1979,
Cancer,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
December 1984,
[Rinsho ketsueki] The Japanese journal of clinical hematology,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
January 1985,
Neoplasma,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
October 1984,
Journal of clinical oncology : official journal of the American Society of Clinical Oncology,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
June 1987,
Seminars in oncology,
H M Kantarjian, and
E H Estey, and
W Plunkett, and
M J Keating, and
R S Walters, and
S Iacoboni, and
K B McCredie, and
E J Freireich
June 1987,
Taiwan yi xue hui za zhi. Journal of the Formosan Medical Association,
