PHARMACOKINETICS OF CIS-DIAMMINEDICHLOROPLATINUM(II) GIVEN AS LOW-DOSE AND HIGH-DOSE INFUSIONS

A pharmacokinetic analysis of cis-diamminedichloroplatinum (IT) (DDP) was conducted comparing low-dose daily bolus infusions, and high-dose drip infusions. Eight patients with gastric cancer were treated with l ow-dose daily bolus infusions of DDP to a total daily dose of 75 mg/m( 2) bid for 5 days. Four patients with esophageal cancer and one patien t with gastric cancer were treated with high-dose drip infusions of DD P to a total daily dose of 70-80 mg/m(2). Side effects were assessed i n all the patients, and the platinum concentration in plasma was deter mined by an atomic absorption method. The peak plasma concentration (C -max) and area under the curve (AUC) were calculated in four cases of the low-dose therapy, and three cases of the high-dose therapy. The si de effects of DDP were evaluated according to the World Health Organiz ation (WHO) grading, paying particular attention to nausea/vomiting, a ppetite loss, renal toxicity, and bone marrow suppression. The inciden ce of nausea/vomiting and appetite loss was significantly reduced with low-dose daily bolus infusions when compared to the high-dose drip in fusions. Bone marrow toxicity and renal toxicity were similar with bot h administration methods, although hydration was required for the high -dose drip infusions to prevent renal toxicity. The peak plasma concen tration (C-max) of total and free platinum, and the area under the cur ve (AUC) of total platinum, were similar with both administration meth ods, while the AUC of free platinum was higher with the low-dose daily bolus infusions compared to the high-dose drip infusions. The time wh en the concentration of total platinum was >1 mu g per mi (holding tim e) was significantly longer with the high-dose drip infusions than wit h the low-dose daily bolus infusions. The present study suggests that low-dose daily bolus infusions of DDP would be useful in reducing gast rointestinal toxicity, without reducing the area under the curve which is important for antitumor activity. (C) 1996 Wiley-Liss, Inc.