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The 1948 antifolate that produced the first chemotherapy remissions in childhood leukaemia and the first cure of a solid tumour; still essential in ALL, lymphoma, osteosarcoma and CNS lymphoma.
Farber (1948) with aminopterin; methotrexate cured choriocarcinoma (1956). Roles: ALL maintenance and CNS prophylaxis (intrathecal), high-dose regimens in osteosarcoma (MAP), PCNSL and Burkitt/DLBCL CNS prophylaxis, GTN, head and neck and bladder (MVAC). Toxicities: mucositis, nephrotoxicity (high dose; glucarpidase rescue), hepatotoxicity, pneumonitis. Also the standard DMARD in rheumatoid arthritis and used in ectopic pregnancy.
Inhibits dihydrofolate reductase, depleting tetrahydrofolate needed for thymidylate and purine synthesis; high doses with leucovorin rescue cross the blood-brain barrier.
1.Methotrexate slips into a pocket on its target.
Oral anticancer drug with an injectable equivalent used for the same indication, so Medicare covers the oral form under Part B (the oral anticancer drug benefit) as well as under Part D; the pharmacy bills whichever applies. High-dose IV methotrexate is Part B and usually inpatient (Part A).
Multi-source generic on low-cost tiers; usually no prior authorisation. Cash prices without insurance are modest.
Sources: Medicare.gov: Chemotherapy · Medicare.gov: Prescription drugs (outpatient, Part B) · Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
Sources: NICE search: methotrexate. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
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| Region | Year | Indication |
|---|---|---|
| US | 1953 | ALL, choriocarcinoma, and later osteosarcoma, breast, head and neck, lung, lymphoma, mycosis fungoides |
Read for the class this product belongs to (high-dose or intrathecal methotrexate) unless the answer names the product. Population figures from the cohorts named, not a prediction for one person. Blank where no source gives a recovery figure.
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The standard-of-care rows on all three trophoblastic pages follow this report and the national centres it describes.
High-dose methotrexate interim maintenance and age-adapted steroid choice are standard in high-risk paediatric B-ALL protocols.
MATRix became the reference induction for fit patients with primary CNS lymphoma and the control arm of later randomised trials.
Pulsed dactinomycin is at least as good as weekly methotrexate for low-risk GTN, but many centres still prefer the multi-day methotrexate-folinic acid schedule, which was not tested here; overall cure approaches 100 percent whichever drug comes first.
The regimen that made extranodal NK/T-cell lymphoma treatable. The usual explanation is that asparaginase is not a substrate of the P-glycoprotein pump this tumour expresses, which would explain why it works where anthracycline-based regimens do not; that mechanism is widely repeated but has been contradicted by at least one series.
EMA/CO remains the first-line regimen for high-risk GTN worldwide; later Charing Cross work added low-dose induction etoposide-cisplatin for women with very high scores.
Query for this drug: (TITLE:"Methotrexate" OR ABSTRACT:"Methotrexate" OR TITLE:"Trexall" OR ABSTRACT:"Trexall" OR TITLE:"Otrexup" OR ABSTRACT:"Otrexup" OR TITLE:"Xatmep" OR ABSTRACT:"Xatmep") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Methotrexate, not a curated reading list.
Shares EMA/CO for high-risk gestational trophoblastic tumours: results from a cohort of 272 patients, Donald Pinkel, Treatment Protocol of the NHL-BFM and the NOPHO Study Groups for Mature Aggressive B-cell Lymphoma and Leukemia in Children and Adolescents, Histological response to induction chemotherapy (osteosarcoma and Ewing sarcoma) and the tags generic, who-essential.
Shares EMA/CO for high-risk gestational trophoblastic tumours: results from a cohort of 272 patients, FIGO Cancer Report 2021: diagnosis and management of gestational trophoblastic disease, Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myeloid Leukemia, Treatment Protocol of the NHL-BFM and the NOPHO Study Groups for Mature Aggressive B-cell Lymphoma and Leukemia in Children and Adolescents and the tags generic, who-essential.
Shares GOG 174: weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia, EMA/CO for high-risk gestational trophoblastic tumours: results from a cohort of 272 patients, FIGO Cancer Report 2021: diagnosis and management of gestational trophoblastic disease, Sidney Farber and the tags generic, who-essential.
Shares EMA/CO for high-risk gestational trophoblastic tumours: results from a cohort of 272 patients, Burkitt leukaemia, Intravascular large B-cell lymphoma, DBCG 82b and 82c and the tags generic, who-essential.
Shares LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis, LCH-III, Perioperative Durvalumab With Neoadjuvant ddMVAC or Gemcitabine/Cisplatin in Patients With Muscle-invasive Bladder Cancer (NIAGARA-2), Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma and the tags generic, who-essential.
Shares Choriocarcinoma of the testis, HIV-associated (AIDS-related) lymphomas, The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest, Testicular germ cell tumours and the tags generic, who-essential.
Shares DBCG 82b and 82c, Alkylating agents and antimetabolites, Small-molecule API synthesis, Buccal mucosa and gingivobuccal cancer (oral cancer in India) and the tags generic, who-essential.
Shares Alkylating agents and antimetabolites, Perioperative Durvalumab With Neoadjuvant ddMVAC or Gemcitabine/Cisplatin in Patients With Muscle-invasive Bladder Cancer (NIAGARA-2), Study to Investigate Outcome of Individualized Treatment in Patients With Metastatic Colorectal Cancer, Extranodal NK/T-cell lymphoma and the tags generic, who-essential.