Disposition and tumour concentrations of platinum in hypoalbuminaemic patients after treatment with cisplatin for cancer of the head and neck.
1 Platinum concentrations in the tumour reached a peak of 3.8 +/- 1.5 micrograms g-1 wet weight tissue at the end of an 8 h intravenous infusion of cisplatin. The tumour concentrations of platinum were higher than the corresponding plasma concentrations (2.5 +/- 0.9 micrograms ml-1) and declined more slowly. 2 Patients with squamous carcinoma of the head and neck had a significantly shorter median survival time if they had low plasma albumin concentrations (less than 40 g l(-1) compared with patients in the normal range, 133 days and 768 days respectively (P less than 0.05) after treatment with cisplatin. 3 No changes in the pharmacokinetics of platinum were detected to account for this poor response of hypoalbuminaemic patients, but plasma albumin concentration was found to be negatively correlated with the first order elimination rate constant. 4 The cumulative urinary excretion of platinum in the first 24 h was not altered by lowered plasma albumin. 5 The concentration of platinum in the tumour did not correlate with the survival time of the patient, but was found to be correlated with the volume of distribution in the post-distributive phase.
Holding
J D
JD
Department of Pharmacology and Therapeutics, University of Liverpool.
Lindup
W E
WE
Bowdler
D A
DA
Siodlak
M Z
MZ
Stell
P M
PM
D000328:Adult; D000368:Aged; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010984:Platinum / Q000097:blood / Q000378:metabolism* / Q000652:urine; D012709:Serum Albumin / Q000172:deficiency*
D012709:Serum Albumin; D010984:Platinum; D002945:Cisplatin