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.