Corpus ID: 5801175

Potentiation of the antitumor activity of methotrexate by concurrent infusion of thymidine.

@article{Semon1978PotentiationOT,
  title={Potentiation of the antitumor activity of methotrexate by concurrent infusion of thymidine.},
  author={J H Semon and Gerald Burr Grindey},
  journal={Cancer research},
  year={1978},
  volume={38 9},
  pages={
          2905-11
        }
}
Abstract The effects of normal metabolites on the toxicity and antitumor activity of methotrexate against leukemia L1210 in DBA/2J mice were evaluated by a system that allows for long-term continuous i.v. infusion of unrestrained mice. In normal female DBA/2J mice, the infusion of methotrexate alone for 48 hr produced a 50% lethal dose of 6 mg/kg/day. Coadministration of thymidine (5 g/kg/day) and methotrexate, followed by an additional 48 hr of thymidine alone, dramatically reduced toxicity… Expand
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49 Citations
Background Citations
6
Methods Citations
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49 Citations

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Citation Type

Influence of concomitant infusion of thymidine and inosine on methotrexate activity in normal and P388-bearing mice.
TLDR
It is concluded that co-administration of inosine and/or thymidine allows the use of methotrexate doses otherwise not tolerated, though with loss of anti-tumor effect. Expand
Chemotherapeutic efficacy of 5-fluorouracil with concurrent thymidine infusion against transplantable colon tumors in rodents.
TLDR
The therapeutic efficacy of 5-fluorouracil given concomitantly with thymidine (TdR) versus that of FU alone at an equitoxic dose was evaluated and showed that, under the conditions employed, TdR did not modify significantly the antitumor activity of F U against rodent colon tumors. Expand
Effect of thymidine on the toxicity and antitumor activity of Cis-diamminedichloroplatinum (II)
TLDR
The data suggest that the cytotoxicity of DDP is increased by TdR only at higher doses of either drug, but that the antitumor activity against P388 murine leukemia is not affected. Expand
Reversal of the in vitro methotrexate suppression of cell-mediated immune response by folinic acid and thymidine plus hypoxanthine.
TLDR
The results indicate that reversal of the methotrexate-induced impairment of cellular immune function depends on several parameters including the concentration of metHotrexate and of the reversing agents as well as the time of exposure of relevant target cells to these agents. Expand
Thymidine enhancement of methotrexate and 5-fluorouracil toxicity in cultured human colon carcinoma
TLDR
Results suggest that less well studied mechanisms of dThd modulation, other than enhanced deoxynucleotide formation or total RNA incorporation, may biochemically enhance FUra toxicity in HCT-8 cells. Expand
Comparison of pharmacokinetics of 5-fluorouracil and 5-fluorouracil with concurrent thymidine infusions in a Phase I trial.
The serum half-life of 5-fluorouracil (5-FUra) in humans is best described as a biexponential decay function, with t1/2 alpha = 7.8 +/- 2.6 (S.E.) min and t1/2 beta = 36.8 +/- 13.5 min during initial… Expand
Synergism between purines and thymidine (TDR) in reversal of methotrexate (MTX) toxicity in mice using continuous infusions.
TLDR
The role of purine is investigated in the reversal by TdR of MTX toxicity and its role in the de novo synthesis of purines and thymidylate is investigated. Expand
Reversal of methotrexate inhibition of colony growth of L1210 leukemia cells in semisolid medium.
TLDR
The use of a high-purine-low-thymidine combination has advantages over the use of leucovorin in controlling toxicity over a wide range of MTX concentrations and in providing some degree of selective protection to normal proliferating cells. Expand
Achievement of long duration methotrexate exposure with concurrent low dose thymidine protection: influence of methotrexate pharmacokinetics.
TLDR
The results indicate that even low doses of thymidine partially protect normal tissues in vivo, and suggest that differences in uptake and release of MTX from tissue deposits must be considered as a source of variation in MTX pharmacokinetics. Expand
Thymidine requirements for the rescue of patients treated with high-dose methotrexate.
TLDR
This study demonstrates that the minimum dose of thymidine required for rescue is in the range of 1 g/sq m/day, demonstrating that the 8-fold larger doses used in previous studies of dThd rescue may have obscured potential selectivity based on differential utilization of d Thd by normal and malignant cells. Expand
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References

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