TY - JOUR
T1 - Sequential use of methotrexate, folinic acid, and cytosine arabinoside in the treatment of acute leukemia
AU - Greenberg, Michael L.
AU - Waxman, Samuel
N1 - Funding Information:
MANY of the drugs used in the treatment of the acute leukemias have a major effect on one phase or another of the cell replicative cycle, as has been recently reviewed \[1, 2\]. A current model of leukemic blast cell replication suggests that only a portion of the blasts are in the active proliferative cycle \[1-3\]. The quiescent cells may be end stage ceils which are destined to die, Go cells which will divide again under proper stimulation, ceEs with a long postmitotic rest time (Gx), or a combination of these. Destruction of the cells in one phase of the cell cycle may result in (1) synchronization of the remaining cells, i.e., a greater than usual fraction will now be in a given phase of the cycle, and/or (2) recruitment, i.e., quiescent cells in a Go or long G1 phase will be stimulated into active replication. A decrease in the number of tumor cells or products of their destruction may *Supported Accepted 18 in March part 1976. by NIH Grants CA-10515 and AMI-6690-01, Chemotherapy Foundation of New York, and United Leukemia Fund. ~'MLG was a scholar of Leukemia Society of America during part of this work.
PY - 1976/8
Y1 - 1976/8
N2 - Methotrexate, folinic acid and cytosine arabinoside were used in sequence over 48 hr in 12 courses of treatment in 3 patients with lymphoblastic and 2 with myelomonoblastic leukemia, all of whom had become resistant to conventional chemotherapy, in an attempt to develop a means of synchronizing and/or recruiting blast cells for more effective chemotherapeutic effect. Three patients had partial, and two had complete remissions. Serial marrow specimens were studied. Methotrexate in vivo and in vitro blocked de novo DNA synthesis; most patients had a compensatory increase in the salvage pathway. The labeling index was unchanged or increased by methotrexate in vivo, and the mitotic index was markedly decreased. Folinic acid "rescue" incompletely restored de novo DNA synthesis but usually increased the labeling index. Cytosine arabinoside then markedly decreased the labeling index. The recovery of labeling and mitotic indices to pretreatment levels took 1-8 days after treatment. These studies demonstrate the biochemical, cellular kinetic and clinical feasibility of this approach to therapy.
AB - Methotrexate, folinic acid and cytosine arabinoside were used in sequence over 48 hr in 12 courses of treatment in 3 patients with lymphoblastic and 2 with myelomonoblastic leukemia, all of whom had become resistant to conventional chemotherapy, in an attempt to develop a means of synchronizing and/or recruiting blast cells for more effective chemotherapeutic effect. Three patients had partial, and two had complete remissions. Serial marrow specimens were studied. Methotrexate in vivo and in vitro blocked de novo DNA synthesis; most patients had a compensatory increase in the salvage pathway. The labeling index was unchanged or increased by methotrexate in vivo, and the mitotic index was markedly decreased. Folinic acid "rescue" incompletely restored de novo DNA synthesis but usually increased the labeling index. Cytosine arabinoside then markedly decreased the labeling index. The recovery of labeling and mitotic indices to pretreatment levels took 1-8 days after treatment. These studies demonstrate the biochemical, cellular kinetic and clinical feasibility of this approach to therapy.
UR - http://www.scopus.com/inward/record.url?scp=0017169727&partnerID=8YFLogxK
U2 - 10.1016/0014-2964(76)90187-0
DO - 10.1016/0014-2964(76)90187-0
M3 - Article
C2 - 1086210
AN - SCOPUS:0017169727
SN - 0014-2964
VL - 12
SP - 617
EP - 623
JO - European Journal of Cancer (1965)
JF - European Journal of Cancer (1965)
IS - 8
ER -