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The treatment of advanced bladder cancer with methotrexate and cis-platinum--a pharmacokinetic study.

Abstract
As part of a phase III study in advanced bladder cancer, 5 patients received methotrexate (MTX) 50 mg/m2 as a single agent every 2 weeks, and with every alternate dose of MTX (i.e. every 4 weeks) cis-platinum (CDDP) 50 mg/m2 was given simultaneously, together with saline hydration and diuresis. The clearance of MTX was measured in a total of 12 courses by serial serum sampling for up to 72 hr following injection. In 4 patients (with a mean pretreatment creatinine clearance of 97 ml/min) there was no significant difference between the clearance of MTX when given alone [mean t1/2 (beta) 3.2 hr] and when given 2 weeks later with concurrent CDDP [mean t1/2 (beta) 2.9 hr]. In 1 patient with a pretreatment creatinine clearance of 52 ml/min the clearance of MTX when given alone (without hydration) was significantly delayed compared with the clearance of MTX when given 2 weeks later concurrently with CDDP and saline hydration [t1/2 (beta) 19 and 4.5 hr respectively]. Of the 5 patients so far treated with MTX-CDDP, 2 have had a partial objective response and 3 have had stable disease (including 2 with a marked subjective response). These data indicate that in patients with satisfactory renal function, low-dose MTX and CDDP may be given concurrently without risk of enhanced drug toxicity.
AuthorsS B Kaye, D McWhinnie, A Hart, R F Deane, P Billaert, J Welsh, R V Milsted, J F Stuart, K C Calman
JournalEuropean journal of cancer & clinical oncology (Eur J Cancer Clin Oncol) Vol. 20 Issue 2 Pg. 249-52 (Feb 1984) ISSN: 0277-5379 [Print] England
PMID6368243 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Creatinine
  • Cisplatin
  • Methotrexate
Topics
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Cisplatin (administration & dosage, blood)
  • Clinical Trials as Topic
  • Creatinine (blood)
  • Humans
  • Kinetics
  • Male
  • Metabolic Clearance Rate
  • Methotrexate (administration & dosage, blood)
  • Middle Aged
  • Time Factors
  • Urinary Bladder Neoplasms (blood, drug therapy)

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