This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Straus, M. J. Articles by Goldin, A. Search for Related Content PubMed PubMed Citation Articles by Straus, M. J. Articles by Goldin, A.

The Effect of the Sequence of Administration of Cytoxan and Methotrexate on the Life-span of L1210 Leukemic Mice

Drug Research and Development [M. J. S., A. G.], Chemotherapy, and Biometry Branch, National Cancer Institute [N. M.], Bethesda, Maryland 20014

The purpose of this study was to determine whether the sequence of administration of two chemotherapeutic agents, cytoxan (Cyt) and methotrexate (MTX), would alter antileukemic effectiveness. CDF₁ mice were inoculated i.p. with 10⁵ L1210 ascites tumor cells. In one experiment, mice were treated with one dose of MTX 2 days after tumor inoculation (Day 2) and one dose of Cyt on Day 4 or 6.

For each group of mice in this study there was a corresponding group that received the same doses of the drugs but for which the order of administration was reversed; i.e., Cyt was given on Day 2 and MTX was given on Day 4 or 6. When the doses of Cyt and MTX were 80 and 30 mg/kg, respectively, significantly longer survivals were noted when Cyt was administered prior to MTX.

In other experiments, MTX was administered in a series of doses at 2-or 4-day intervals to L1210 mice. When a high dose of Cyt (120 mg/kg) was substituted for a regularly scheduled dose of MTX, the earlier the substitution, the longer was the survival. No effect of replacement was noted when Cyt (40 mg/kg) was substituted for MTX. When a higher dose of MTX (36 mg/kg) replaced a dose of MTX (4 mg/kg), earlier substitution appeared to increase survival.

The advantage to therapy of a high priming dose may reflect a prior observation that the percentage kill of tumor cells of cell cycle stage-specific agents such as MTX is greater for smaller populations of tumor cells. Early administration of a high priming dose of Cyt or MTX apparently lowers the tumor cell population so that scheduled doses of MTX can kill tumor cells more effectively.

Received 5/13/71. Accepted 10/ 7/71.