Methotrexate breast cancer

Higher response rates are seen when 5-FU is used in combination with other agents, such as cyclophosphamide and methotrexate (breast cancer), cisplatin (head and neck cancer), and with oxaliplatin or irinotecan in colon cancer. The combination of 5-FU and oxaliplatin or irinotecan has become the standard first-line treatment for patients with metastatic colorectal cancer. The use of 5-FU in combination regimens has improved survival in the adjuvant treatment for breast cancer, and with oxaliplatin and leucovorin, for colorectal cancer. 5-FU also... 

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

Cyclophosphamide is a component of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) and other drug combinations used in the treatment of breast cancer. Cyclophosphamide in combination may produce complete remissions in some patients with ovarian cancer and oat cell (small cell) lung cancer. Other tumors in which benehcial results have been reported include non-oat cell lung cancers, various sarcomas, neuroblastoma, and carcinomas of the testes, cervix, and bladder. Cyclophosphamide also can be employed as an alternative to azathioprine in suppressing immunological rejection of transplant organs. 

Sohn KJ, Croxford R, Yates Z et al. Effect of the methylenetetrahydrofolate reductase C677T polymorphism on chemosensitivity of colon and breast cancer cells to 5-fluorouracil and methotrexate. J... 

Methotrexate Inhibits DHFR inhibits TS inhibits de novo purine nucleotide synthesis Breast cancer, head and neck cancer, osteogenic sarcoma, primary central nervous system lymphoma, non-Hodgkin s lymphoma, bladder cancer, chorioca rcinoma Mucositis, diarrhea, myelosuppression with neutropenia and thrombocytopenia... 

Advantage is taken of the properties of antimctabolitcs in chemotherapy. In cancer chemotherapy, several antimetabolites are used. These include methotrexate, 6-mercaptopunne, 6-thioguanine, 5-fluorouracil, and cystine arabinoside. In the chemotherapy of metastatic breast cancer, 5-fluorouracil and methotrexate, in combination with cyclophosphamide, have been used. Antimetabolites, sometimes along with corticosteroids, are used in the therapy of various autoimmune diseases, such as thrombocytenic purpura, thyroiditis, Goodpasture s syndrome, among others. 

Distante V, Bolognesi A, Aldrighetti D, Farris A. Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast cancer patients results of the Italian Breast Cancer Adjuvant Study Group 02 randomized trial. J Clin Oncol 2000 18(14) 2718-27. 

CMF Cyclophosphamide (Cytoxan), methotrexate, 5-fluorouracil Breast cancer... 

Cyclophosphamide (Cytoxan and Endoxan) is used in the treatment of Hodgkin s disease, lymphosarcoma, and other lymphomas. It is employed as a secondary drug in patients with acute leukemia and in combination with doxorubicin in women with breast cancer. A drug combination effective in the treatment of breast cancer is cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP). Cyclophosphamide is also an immunosuppressive agent. The toxicity of cyclophosphamide causes alopecia, bone marrow depression, nausea and vomiting, and hemorrhagic cystitis. 

Breedveld P, Zelcer N, Pluim D, et al. Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles potential role for breast cancer resistance protein in clinical drug-drug interactions. Cancer Res 2004 64 5804— 5811. 

Knoop AS, Knudsen H, Balslev E, Rasmussen BB, Overgaard J, Nielsen KV, et al. retrospective analysis of topoisomerase lla amplifications and deletions as predictive markers in primary breast cancer patients randomlyassignedtocyclophosphamide, methotrexate, andfluorouracilor cyclophosphamide, epirubicin, and fluorouracil Danish Breast Cancer Cooperative Group. J Clin Oncol 2005 23(30) 7483-90. 

Ross, D. D., Schneider, E. (2000). Methotrexate cross-resistance in a mitoxantrone-seiected muitidrug-resistant MGF7 breast cancer ceii iine is attributabie to enhanced energy-dependent drug efflux. Cancer Res. 60, 3514-3521. 

Gelman RS, Taylor SG. Cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in women more than 65 years old with advanced breast cancer The elimination of age trends in toxicity by using doses based on creatinine clearance. J Clin Oncol 1984 2 1404-13. 

Fluorouracil has been the mainstay of treatment of gastrointestinal tract tumours for the last 50 years. Combined with cyclophosphamide and methotrexate, the so-called CMF regimen is a gold standard treatment for many women with either early or advanced breast cancer. 

The idea that the degree of leukocjde suppression can be used to predict the success of adjuvant chemotherapy has been apphed to combined treatment with cyclophosphamide, methotrexate, and 5-fluorouracil for breast cancer the lower the nadir leukocjde count, the greater the incidence of metastatic disease-free survival (14). 

Two-thirds of patients treated with cyclophosphamide orally for 4 months plus intravenous 5-fluorouracil and methotrexate for breast cancer developed Barrett s epithelium (16), perhaps as a result of esophagitis, rather than through mucosal re-epithelialization by undifferentiated stem cells (17). 

Volk, E.L. and Schneider, E. (2003) Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Research, 63, 5538—5543. 

Folate analogues, such as methotrexate (Figure 27-3), are folate antagonists. They block production of FH2 and FH4 by dihydrofolate reductase and lead to diminished purine biosynthesis (inhibition of reactions 3 and 9 in Figure 27-8). Methotrexate also affects metabolism of amino acids and pyrimidine (inhibition of thymidylate synthesis) and inhibits DNA, RNA, and protein synthesis. It is effective in the treatment of breast cancer, cancer of the head and neck, choriocarcinoma, osteogenic sarcoma, and acute forms of leukemia. High doses of methotrexate can be tolerated provided that the patient also receives folinic... 

Cytotoxic drags that have been used alone and in combination as adjuvant therapy in breast cancer include doxorubicin, epirubicin, cyclophosphamide, methotrexate, fluorouracil, paclitaxel, docetaxel, melphalan, prednisone, vinorelbine, and vincristine. The most common combination chemotherapy regimens employed in the adjuvant and metastatic setting are listed in Table 125-11. 

Bonadonna G, Valagussa P, MoUtemi A, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer The results of 20 years of follow-up. N Engl J Med 1995 332 901-906. 

Jonat W, Kaufmann M, Sauerbrei W, et al. Goserelin versus cyclophosphamide, methotrexate and fluorouracil as adjuvant therapy is premenopausal patients with node-positive breast cancer The Zoladex Early Breast Cancer Research Association Study. J Clin Oncol 2002 20 4628-4635. 

In addition, 5-FU and methotrexate are used to treat certain forms of breast cancer, and methotrexate is the drug of choice for the treatment of choriocarcinoma in women. It is also effective in the treatment of psoriasis, a disease in which there is an over-proliferation of epidermal cells in the skin. Finally, it is worth recalling that azidothymidine (AZT) was first synthesised in 1964 as a potential anti-metabolite for cancer chemotherapy, but proved to be ineffective in this role. Its subsequent efficacy as an inhibitor of viral reverse transcriptase in the treatment of HIV infections has assured its place in the history of the 20th century. 

Menard S, Valagussa P, Pilotti S, et al. Response to cyclophosphamide, methotrexate, and fluorotrracil in lymph node-positive breast cancer according to HER2 overexpression and other tumor biologic variables. / Clin Oncol. 2001 19 329-335. 

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