The treatment of advanced bladder cancer with methotrexate and cis-platinum--a pharmacokinetic study.
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.
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000097:blood*; D002986:Clinical Trials as Topic; D003404:Creatinine / Q000097:blood; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000097:blood*; D008875:Middle Aged; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000188:drug therapy
D003404:Creatinine; D002945:Cisplatin; D008727:Methotrexate