Clinical use of methotrexate--with emphasis on use of high doses

The rationale for and the clinical use of regimens that utilize methotrexate (MTX) in high dose (greater than 500 mg/m2) are reviewed. Advantages of high pulse doses are (a) increased cell kill; (b) prevention or delay of resistance; (c) penetration into the cerebrospinal fluid (CSF); and (d) relative lack of toxicity, if used with appropriate monitoring and patient surveillance. Disadvantages are its cost and the cost of patient followup required. Some examples of its use in combination illustrate the point that antagonistic as well as synergistic antitumor or antinormal cell effects can result, depending upon the sequence of administration of MTX and another drug.