Plasma amino acids during high-dose methotrexate-citrovorum “rescue”

Hilton, Mary A.; Kmetz, Donald R.; Patel, Chandrakant C.

doi:10.1016/0006-2944(76)90003-x

Cited by 2 publications

(6 citation statements)

References 8 publications

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“…An elevation of 57 1070 in plasma PHE/TYR in patient A after 22 hours correlated with severe toxicity, which was treated with additional CFR [8]. Patient F, during her third treatment, showed a change of 410% in plasma PHE/TYR after an 8-hourlonger interval (30 hours), and this elevation was also associated with severe toxicity.…”

Section: Resultsmentioning

confidence: 97%

“…Therefore, elevations of plasma PHE/ TYR during HDMTX-CFR should parallel the intracellular concentrations of MTX in the liver, where PHE hydroxylase is located, without interference from the rescue protocol. In patient A, plasma PHE/TYR was maximal 22 hours after beginning the infusion of HDMTX; five injections of CF (at 6, 10, 14, 18, and 22 hours) had been administered before this peak in plasma PHE was observed [8]. cannot be recycled to functional FH, in the presence of methotrexate (above left).…”

Section: Disc Usslonmentioning

confidence: 98%

“…1). Perhaps surprisingly, plasma levels of TY R remained relatively constant during the 4 days following infusion of MTX [8]. This suggests that formation of TYR from PHE by liver PHE hydroxylase is not required for maintenance of normal plasma levels of TYR in these patients; plasma TYR is apparently mobilized from tissue proteins.…”

Section: Introductionmentioning

confidence: 95%

“…Patient A was discussed previously [8]. He had an unresectable osteosarcoma and underwent a single treatment with HDMTX-CFR which produced severe toxicity.…”

Section: Patientsmentioning

confidence: 99%

“…We reported earlier a marked elevation of plasma phenylalanine (PHE) in a patient who exhibited toxicity to HDMTX-CFR [8]. This elevation of plasma PHE persisted throughout the course of the CFR and was attributed to inhibition by MTX of dihydropteridine reductase, a component of the PHE hydroxylase system of the liver, which initiates the catabolism of excess PHE via oxidation to tyrosine (TYR) (see Fig.…”

Section: Introductionmentioning

confidence: 99%

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Plasma phenylalanine: Tyrosine ratios during high‐dose methotrexate‐citrovorum “rescue”

Hilton

Patel

Bertolone

et al. 1982

Med. Pediatr. Oncol.

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We have measured phenylalanine and tyrosine in the plasma of patients with osteogenic sarcoma undergoing chemotherapy with high-dose methotrexate (HDMTX) citrovorum factor rescue (CFR). During 14 treatments in six different patients, the phenylalanine to tyrosine ratio (PHE/TYR) at 21 to 38 hours was elevated over pretreatment levels. The observed increase in plasma phenylalanine is attributed to inhibition by MTX of the phenylalanine hydroxylase system of the liver, which is not folate-dependent and thus is not corrected by administration of CV. A post-infusion increase in PHE/TYR of 571% after 22 hours in one patient and of 410% after 30 hours in another were associated with marked MTX toxicity. The greatest increase in PHE/TYR seen in a patient who did not experience toxicity was was 249% in 21 hours. Thus, in this group of patients, there appears to be a correlation between evidence of clinical MTX toxicity and the magnitude of the percentage increase in PHE/TYR in the plasma, which indicates inhibition of a liver enzyme and thus reflects the intracellular concentration of MTX.

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Section: Resultsmentioning

confidence: 97%

Section: Disc Usslonmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 95%

“…Patient A was discussed previously [8]. He had an unresectable osteosarcoma and underwent a single treatment with HDMTX-CFR which produced severe toxicity.…”

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Plasma phenylalanine: Tyrosine ratios during high‐dose methotrexate‐citrovorum “rescue”

Hilton

Patel

Bertolone

et al. 1982

Med. Pediatr. Oncol.

Self Cite

View full text Add to dashboard Cite

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Daily profiles of plasma phenylalanine and tyrosine in patients with osteogenic sarcoma during treatment with high‐dose methotrexate‐citrovorum rescue

Hilton

Bertolone

Patel

1989

Med. Pediatr. Oncol.

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Three adolescents and one child with osteosarcoma were studied during multiple courses of high-dose methotrexate, citrovorum factor rescue (HDMTX-CFR), with one adolescent treated intermittently over a period of 6 years. Plasma phenylalanine (Phe) and tyrosine (Tyr) were measured immediately before the infusion of MTX and then daily until serum MTX fell below 10(-7) M. At 24 hours, all showed marked increases in Phe and in the Phe/Tyr ratio. This suggests inhibition of dihydropteridine reductase (DHPR) which, in association with hepatic Phe hydroxylase, controls plasma concentrations of Phe. Inhibition of this enzyme system is not relieved by CFR. In the adolescent patients, although MTX levels in plasma declined steadily, Phe concentrations, which fell between 24 and 48 hours, rose to a new peak at 4-7 days. Possible reasons for this secondary increase are discussed. The patient with the longest exposure to HDMTX showed an increase in pretreatment Phe/Tyr ratios with time, suggesting damage to liver parenchymal cells not indicated by standard tests of liver function. Evaluation of plasma Phe during the course of HDMTX-CFR may permit assessment of intracellular concentrations of MTX or its metabolites in the liver without interference by CFR.

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Plasma amino acids during high-dose methotrexate-citrovorum “rescue”

Cited by 2 publications

References 8 publications

Plasma phenylalanine: Tyrosine ratios during high‐dose methotrexate‐citrovorum “rescue”

Plasma phenylalanine: Tyrosine ratios during high‐dose methotrexate‐citrovorum “rescue”

Daily profiles of plasma phenylalanine and tyrosine in patients with osteogenic sarcoma during treatment with high‐dose methotrexate‐citrovorum rescue

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