title: First-pass uptake of methotrexate after intra-arterial bolus injection in human head and neck cancers.
abstract: The aim of this study was to quantify first-pass uptake of methotrexate into tumour and healthy tissue after intra-arterial (i.a.) injection in patients with head and neck cancers. Twenty-one patients were studied; during surgery, a bolus injection of 10 mg of 3H-labelled methotrexate was administered into the tumour-supplying artery. At 15-20 s after injection, and again 2-3 h later, a biopsy of the tumour and of surrounding healthy tissue was taken and radioactivity was measured. In 8 of 17 pretreated patients the biopsy specimens contained no tumour cells. In tumour-bearing patients, radioactivity in tumour was three times higher than in healthy tissue (P = 0.006). In tumour-negative patients there was no difference in activity between the two biopsy sites (P = 0.889). However, after 2-3 h the concentration of methotrexate in all surgical specimens returned to near background level and the initial difference between tumour-positive and tumour-negative samples was lost. Our results show that i.a. injection of methotrexate does not necessarily lead to high tumour cell exposure.
authors.affiliation: Department of Clinical Pharmacology, Vienna University Hospital, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Blöchl-Daum
authors.forename: R
authors.initials: R
authors.lastname: Mader
authors.forename: W
authors.initials: W
authors.lastname: Millesi
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: H
authors.initials: H
authors.lastname: Rainer
authors.forename: R
authors.initials: R
authors.lastname: Eglmeier
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: G
authors.initials: G
authors.lastname: Zanaschka
authors.forename: H G
authors.initials: HG
authors.lastname: Eichler
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D012512:Sarcoma, Ewing / Q000188:drug therapy
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate