CISPLATIN PHARMACOKINETICS IN ELDERLY PATIENTS

The treatment of elderly patients with cancer may be difficult because of the narrow therapeutic index of antineoplastic drugs, the decline in the performance of organs and functions, and frequent comorbidity. In these patients, therapeutic drug monitoring may be useful in optimizing chemotherapy. Six patients older than 70 years with a variety of solid tumors received a total of 21 cycles of cisplatin (DDP)-based chemotherapy program (DDP dose, 50- 65 mg/m(2)). Total and ultrafilterable platinum (Pt) were determined in plasma and urine during the first cycle of the therapy by means of atomic absorption spectroscopy. Pharmacokinetic parameters were analyzed with use of a two-compartment open model. The treatment was generally well tolerated. The most important side effects were a significant increase in serum creatinine level (from 0.98 to 1.23 mg/dl) and a decrease in creatinine clearance (from 44.4 to 38.9 ml/min) in comparison with pretreatment values. The mean decrease in hemoglobin levels was slight. The values of the main pharmacokinetic parameters of total Pt agreed well with the data obtained with other adult patients. Total and ultrafilterable Pt had a short distribution phase (t(1/2)alpha = 0.35 and 0.54 h, respectively) followed by a prolonged elimination phase (t(1/2)beta = 63.08 and 58.91 h, respectively). A reduced ability to clear ultrafilterable Pt (Cl-T = 123.52 ml h(-1) kg(-1)) was evident and, as a result, the area under the curve increased (15.47 mg h L(-1)). The limited number of patients and the concomitant use of other agents prevent any firm conclusions. However, the documented impaired clearance of ultrafilterable Pt suggests that it may be safer in the elderly to use DDP at lower doses than in the adult and that this is associated with optimal drug exposure.