METHOTREXATE, the most widely used antimetabolite in cancer chemotherapy, has an essential role in the treatment of such diverse diseases as acute lymphocytic leukemia, non-Hodgkin's lymphoma, oste...

The pharmacology and clinical use of methotrexate

High-dose methotrexate (HDMTX) with leucovorin (LV) rescue has been used as a therapeutic strategy in oncology for more than a decade. Administration of HDMTX results in tumoricidal plasma concentrations of the drug without significant host toxicity, provided that plasma MTX levels are monitored and LV rescue is properly administered. The original premise of LV rescue was that the provision of reduced folate to normal cells would circumvent the metabolic block produced by MTX and allow resumption of DNA synthesis, although the presumed therapeutic selectivity of leucovorin has not yet been adequately explained. Despite a strong pharmacologic rationale and a vast clinical experience, HDMTX with leucovorin rescue has not been shown to be unequivocally superior to conventional doses of MTX in any clinical situation except, perhaps, for treatment of osteogenic sarcoma and childhood acute leukemia. While HDMTX is an important component of effective treatment regimens for these diseases, its precise contribution to the success of these regimens remains undefined. Although HDMTX can theoretically overcome all known mechanisms of MTX resistance, no data exist to suggest that this can be accomplished in the clinic. Thus, this well-known but poorly understood treatment regimen must remain a subject of clinical investigation rather than a part of routine clinical practice.

High-dose methotrexate: a critical reappraisal.

Vitamins B9 (folate) and B12 are essential water-soluble vitamins that play a crucial role in the maintenance of one-carbon metabolism: a set of interconnected biochemical pathways driven by folate and methionine to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation. Dietary deficiencies in B9 and B12, or genetic polymorphisms that influence the activity of enzymes involved in the folate or methionine cycles, are known to cause developmental defects, impair cognitive function, or block normal blood production. Nutritional deficiencies have historically been treated with dietary supplementation or high-dose parenteral administration that can reverse symptoms in the majority of cases. Elevated levels of these vitamins have more recently been shown to correlate with immune dysfunction, cancer, and increased mortality. Therapies that specifically target one-carbon metabolism are therefore currently being explored for the treatment of immune disorders and cancer. In this review, we will highlight recent studies aimed at elucidating the role of folate, B12, and methionine in one-carbon metabolism during normal cellular processes and in the context of disease progression.

B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease.

Gastrointestinal toxicity of chemotherapeutic agents

THE folic acid antagonists were shown to have antileukemic activity by Farber and his colleagues in 1948.1 Since then the prototypical folic acid antagonist, methotrexate, has been found effective ...

New Approaches to Cancer Chemotherapy with Methotrexate

Summary The effect of “leucovorin rescue” on the therapeutic index of methotrexate in epidermoid carcinomas of the head and neck was studied. Sixteen patients received maximally tolerated doses of methotrexate alone as 30-hr i.v. infusions at 2-week intervals and 44% responded. Significant hematological toxicity and 4 drug-related deaths were incurred. Twenty-five patients received higher doses of methotrexate followed by leucovorin rescue as 36- to 42-hr i.v. infusions every 2 weeks. This group experienced a response rate of 60% with fewer cases of severe toxicity. Seventeen of this group received more than 500 mg/sq m as a maximal dose and had a response rate of 76% with two drug-related deaths, while those receiving smaller doses had a response rate of only 25%. Serum methotrexate levels were proportional to the dose of drug. Leucovorin rescue enhances the therapeutic index of high-dose methotrexate infusions in epidermoid carcinomas of the head and neck.

https://cancerres.aacrjournals.org/content/canres/33/7/1729.full.pdf

Improved therapeutic index of methotrexate with "leucovorin rescue".

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Mosher Mb

Author Tools

Chat about Author

Papers

Improved therapeutic index of methotrexate with "leucovorin rescue".