Methotrexate gastric cancer

Further studies have validated this hypothesis, in part,4 and ultimately this inventive premise was borne out in clinical practice. As a result, 5-FU (5) was eventually approved for treatment of solid tumors, such as breast, colorectal, and gastric cancers. Marketed as Adrucil when administered intravenously, 5-FU can be used either as monotherapy or combination therapy with various cytotoxic drugs and biochemical modulators, such as leucovorin and methotrexate.5 Because 5-fluorouracil is not orally bioavailable, it must be administered by continuous infusion to optimize its efficacy due to its short half-life in plasma. In addition, 5-FU has poor selectivity toward tumors in vivo, and its distribution into tissues such as bone marrow, the gastrointestinal tract, the liver and skin causes high incidences of toxicity. In addition, in spite of its limited lipid solubility, 5-fluorouracil diffuses readily across the blood-brain barrier into cerebrospinal fluid and brain tissue.1,5... 

Murad, AM. et al. 1993. Modified therapy with 5-fluorouracil, doxorubicin and Methotrexate in advanced gastric cancer. Cancer. 72 37-41. 

Methotrexate is a folic acid antagonist that inhibits the enzyme dihydrofolate reductase. This agent is mainly used in the treatment of both cancer [trophoblastic neoplasms, leukemias, breast carcinoma, carcinoma of gastric, esophagus, testes, lymphomas] and non-cancer diseases [psoriasis rheumatoid arthritis]. Recent successful results using high-dose [>lg/ m ] methotrexate followed by leucoverin in the treatment of head and neck carcinomas and osteosarcoma has led to a more widespread use of this therapy in patients with these and other tumors. 

Importantly, OATPl B3 is highly expressed in certain gastric, colon, and pancreatic cancers, indicating that transporter expression may alter tumor sensitivity to methotrexate treatment [82]. 

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