Abstract
Thirty-two patients with head and neck carcinoma received a multidrug chemotherapy protocol including low dose methotrexate (LDMTX) (30 mg/m 2 ) and cisplatin as their initial treatment. A sensitive immunoenzymatic technique was used for systematic MTX blood monitoring (0–56 hr) in all patients. The MTX-related side effects observed in 15 patients (47%) were significantly associated with an increase in systemic drug exposure occurring early during drug infusion. The average end-of-infusion concentration varied from 8 × 10 −7 M for nontoxic patients to 1.45 and 3.12 10 −6 M for moderately and severely toxic patients respectively. The area under the curve (AUC) (0–56 hr) was also directly related to the increase in side-effects. Total body clearance was reduced in an inverse manner. Volumes of distribution and terminal elimination half-lives were not related to the presence or intensity of MTX side-effects. Based on these data, the institution of folinic acid rescue adapted to the MTX blood concentration, a measure previously not suggested for LDMTX, completely prevented severe toxicity in a subsequent series of 26 patients without modification of the response rate.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
