Methotrexate cancer

Since the late 1940s, when Farber treated leukemia with methotrexate, cancer therapy with cytotoxic drugs made enormous progress. Chemotherapy is usually integrated with other treatments such as surgery, radiotherapy, and immunotherapy, and it is clear that postsurgery, it is effective with solid tumors. This is due to the fact that only systemic therapy can attack micrometastases. 

S.J. Friedman and P. Skehan. Morphological differentiation of human choriocarcinoma cells induced by methotrexate. Cancer Res. 39 1960-1967 (1979). 

Sonneveld P, Schultz FW, Nooter Kand Elahlen K. 1986. Pharmacokinetics of methotrexate and 7-hydroxymethotrexate in plasma and bone marrow of children receiving, low-doses oral methotrexate. Cancer Chemother Pharmacol 18 111-118. 

Weinstein JN, Magin RL, Cysyk RL, et al. Treatment of solidL1210 murine tumors with local hyperthermia and temperature sensitive liposomes containing methotrexate. Cancer Res 1980 40 1388-1395. 

V Raso, R Schrieber. A rapid and specific radioimmunoassay for methotrexate. Cancer Res. 35 1407, 1975. 

Altered excretion Competition for transport systems in kidney Elimination of methotrexate (cancer chemotherapy) inhibited by probenecid (for gout)... 

Sketris IS, Farm er PS, Fraser A. Effect of vitamin C on tiie excretion of methotrexate. Cancer Treat Rep (1984) 68, 446-7. 

Reid T, Yuen A, Catolico M, Carlson RW. Impact of omeprazole on the plasma clearance of methotrexate. Cancer ChemotherPharmacol 993) 33, 82-4. 

Innocenti F, Danesi R, Di Paolo A, Lorn B, Favre C, Nardi M, Bocci G, Nardini D, Macchia P, Del Tacca M. Clinical and e q)erimental pharmacokinetic interaction between 6-mercaptop-urine and methotrexate. Cancer Chemother Pharmacol 996) 37,409-14. 

Shamash J, Earl H, Souhami R. Acetazol-amide for alkalinisation of urine in patients receiving high-dose methotrexate. Cancer Chemother Pharmacol 1991 28 150-1. 

Folate antagonists (eg, methotrexate and certain antiepileptics) are used ia treatment for various diseases, but their adininistration can lead to a functional folate deficiency. Folate utilization can be impaired by a depletion of ziac (see Zinc compounds). In humans, the intestinal bmsh border folate conjugase is a ziac metaHoenzyme (72). One study iadicates that the substantial consumption of alcohol, when combiaed with an iaadequate iatake of folate and methionine, may iacrease the risk of colon cancer (73). Based on this study, it is recommended to avoid excess alcohol consumption and iacrease folate iatake to lower the risk of colon cancer. 

Ms. Thompson has cancer of the lung and will begin a treatment regimen with methotrexate. Discuss important preadministration assessments you would perform before beginning therapy with methotrexate. 

D. (1978). Effect of lipid vesicle (liposome) encapsulation of methotrexate on its chemotherapeutic efficacy in solid rodent tumors. Cancer Res., 38, 2848-2853. 

Panetta JC, Wall A, Pui CH, Rolling MV, Evans WE. Methotrexate intracellular disposition in acute lymphoblastic leukemia a mathematical model of gamma-glutamyl hydrolase activity. Clin Cancer Res 2002 8 2423-9. 

Panetta JC, Yanishevski Y, Pui CH, Sandlund JT, Rubnitz J, Rivera GK et al. A mathematical model of in vivo methotrexate accumulation in acute lymphoblastic leukemia. Cancer Chemother Pharmacol 2002 50 419-28. 

Zaharko DS, Dedrick RL, Bischoff KB, Longstreth JA, Oliverio VT. Methotrexate tissue distribution prediction by a mathematical model. / Natl Cancer Inst 1971 Apr 46(4) 775-84. 

Dedrick R, Bischoff KB, Zaharko DS. Interspecies correlation of plasma concentration history of methotrexate (NSC-740). Cancer Chemother Rep 1970 Apr 54(2) 95-101. 

The combination of methotrexate and UVB seems to be synergistic responses may occur with lower cumulative doses of both methotrexate and UVB. However, stopping methotrexate may cause rebound21,33 and there is some concern about photosensitivity.21 Methotrexate and PUVA have been used together in patients refractory to other treatments however, there is additive carcinogenesis (especially increasing the risk of squamous cell cancer) and subacute phototoxicity.21... 

The combination of cyclosporine with calcipotriol may be more efficacious than either agent used alone.21,37 Cyclosporine and SCAT may also be effective.21,38 However, cyclosporine should not be used concurrently with PIJVA there is a well-documented increased risk of squamous cell cancer and the combination may have a negative effect on lesion clearance.21 The combination of cyclosporine with methotrexate is extremely effective and minimizes toxicity from either agent as discussed. Cyclosporine has also been used successfully with mycophenolate mofetil38 and etanercept.29... 

Cytotoxic drugs that have been used alone and in combination as adjuvant therapy in breast cancer include doxorubicin, epirubicin, cyclophosphamide, methotrexate, fluorouracil,... 

C, cytarabine ASP, asparaginase CALCB, Cancer and Leukemia Croup B CNS, central nervous system CTX, cyclophosphamide DEX, dexamethasone DNR, daunorubicin DOX, doxorubicin IT, intrathecal captopurine MTX, methotrexate PRED, prednisone TG, thioguanine VCR, vincristine. 

Methotrexate Dihydrofolate reductase Cancer, bacterial infection... 

An antimetabolite interferes with the normal cellular metabolites. For instance, it can act as an inhibitor of one or more enzymes whose substrates are metabolites. Others are incorporated into macromolecules instead of the metabolites. Development of antimetabolites exhibiting anti-cancer activity met with the greatest success for analogues of metabolites involved in the biosynthesis of nucleic acids and of cofactors containing nitrogenous bases. Compounds such as 5-fluorouracyl and methotrexate are remarkably effective against human cancers, even though they feature host toxicity. 

Abe, T., et al. LST-2, a human liver-spedfic organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology 2001, 120, 1689—1699. 

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