Carboplatin and etoposide pharmacokinetics in patients with testicular teratoma

The pharmacokinetics of carboplatin and etoposide were studied in four testicular teratoma patients receiving four courses each of combination chemotherapy consisting of etoposide (120 mg/m2 daily x 3); bleomycin (30 mg weekly) and carboplatin. The carboplatin dose was calculated so as to achieve a constant area under the plasma concentration vs time curve (AUC) of 4.5 mg carboplatin/ml x min by using the formula: dose = 4.5 x (GFR + 25), where GFR is the absolute glomerular filtration rate measured by 51Cr-EDTA clearance. Carboplatin was given on either day 1 or day 2 of each course and pharmacokinetic studies were carried out in each patient on two courses. Etoposide pharmacokinetics were also studied on two separate courses in each patient on the day on which carboplatin was given and on a day when etoposide was given alone. The pharmacokinetics of carboplatin were the same on both the first and second courses, on which studies were carried out with overall mean +/- SD values (n = 8) of 4.8 +/- 0.6 mg/ml x min, 94 +/- 21 min, 129 +/- 21 min, 20.1 +/- 5.41, 155 +/- 33 ml/min and 102 +/- 24 ml/min for the AUC, beta-phase half-life (t 1/2 beta), mean residence time (MRT), volume of distribution (Vd) and total body (TCLR) and renal clearances (RCLR), respectively. The renal clearance of carboplatin was not significantly different from the GFR (132 +/- 32 ml/min). Etoposide pharmacokinetics were also the same on the two courses studied, with overall mean values +/- SD (n = 8) of: AUC = 5.1 +/- 0.9 mg/ml x min, t 1/2 alpha = 40 +/- 9 min, t 1/2 beta = 257 +/- 21 min, MRT = 292 +/- 25 min, Vd = 13.3 +/- 1.31, TCLR = 46 +/- 9 ml/min and RCLR = 17.6 +/- 6.3 ml/min when the drug was given alone and AUC = 5.3 +/- 0.6 mg/ml x min, t 1/2 alpha = 34 +/- 6 min, t 1/2 beta = 242 +/- 25 min, MRT = 292 +/- 25 min, Vd = 12.5 +/- 1.81, TCLR = 43 +/- 6 ml/min and RCLR = 13.4 +/- 3.5 ml/min when it was given in combination with carboplatin. Thus, the equation used to determine the carboplatin accurately predicted the AUC observed and the pharmacokinetics of etoposide were not altered by concurrent carboplatin administration. The therapeutic efficacy and toxicity of the carboplatin-etoposide-bleomycin combination will be compared to those of cisplatin, etoposide and bleomycin in a randomised trial.