Background : Hematologic toxicity of an antineoplastic drug, carboplatin, is largely dependent on its pharmacokinetics. Its therapeutic efficacy may be related to plasma drug exposure. Dosage adjustment based on isotopic determination of glomerular filtration rate has been proposed, but its ambulatory use is not yet conceivable. The dosage adjustment based on a patient's creatinine clearance relies on accurate measurement of urine volume per unit time and can be done with ease. Purpose : A population pharmacokinetics study was undertaken to determine a relationship between carboplatin clearance and patient characteristics. A predictive formula was derived that was then prospectively evaluated, and its outcome was compared with that obtained by other methods available to predict carboplatin clearance. Methods : Plasma carboplatin pharmacokinetics determined as ultrafilterable platinum in 70 patients (age range, 23–84 years) treated with different combination regimens that included carboplatin at doses ranging from 184 mg to 950 mg (1-hour intravenous infusion) for various tumor types. Data were analyzed using the nonlinear mixed effects model (NONMEM). The data from 34 patients (46 cycles) were utilized to derive the most predictive formula. The reliability of the formula was subsequently evaluated by analyzing the data obtained from 36 other patients (43 cycles). Results : Carboplatin clearance (mL/min) was found to be best predicted by the following formula: 0.134 weight + [218 weight (1 - 0.00457 age) (1 - 0.314 sex)]/creatinine expressed in micromolar concentration (with weight in kg, age in years, and sex = 0 if male and sex = 1 if female). Prospectively, this formula predicted the carboplatin clearance with good precision (median absolute percent error of 10% [range, 0% to 30%]) and minimal bias (median percent error of 2% [range, -25% to 30%]). This method of prediction was as accurate as the one derived from the measurement of glomerular filtration rate following the injection of 51 chromium-EDTA. Conclusion : This formula for the determination of carboplatin clearance can permit individualized determination of carboplatin dosage in adults by simply multiplying the calculated carboplatin clearance by the area under the curve for the desired dosage administration. [J Natl Cancer Inst 87: 573-580, 1995]

The elderly comprise the majority of patients with cancer and are the recipients of the greatest amount of chemotherapy. Unfortunately, there is a lack of data to make evidence-based decisions with regard to chemotherapy. This is due to the minimal participation of older patients in clinical trials and that trials have not systematically evaluated chemotherapy. This article reviews the available information with regard to chemotherapy and aging provided by a task force of the International Society of Geriatric Oncology (SIOG). Due to the lack of prospective data, the conclusions and recommendations made are a consensus of the participants. Extrapolation of data from younger to older patients is necessary, particularly to those patients older than 80 years, for which data is almost entirely lacking. The classes of drugs reviewed include alkylators, antimetabolites, anthracyclines, taxanes, camptothecins, and epipodophyllotoxins. Clinical trials need to incorporate an analysis of chemotherapy in terms of the pharmacokinetic and pharmacodynamic effects of aging. In addition, data already accumulated need to be reanalyzed by age to aid in the management of the older cancer patient.