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Pharmacokinetics of consecutive low-dose cisplatin.

The present study investigated the optimal mode of cisplatin (CDDP) dosing in terms of pharmacokinetics. Ten patients with stage Ic ovarian cancer were randomly assigned to receive either bolus-CDDP (70 mg/m(2), 2-h infusion on day 1) or consecutive low-dose (CLD)-CDDP (10 mg/m(2), 4-h infusion for 7 consecutive days) in the adjuvant setting. Maximum concentration (C-max) of total and filterable platinum for the bolus-CDDP group were significantly higher than those for the CLD-CDDP group. Whereas, filterable drug exposure defined by the area under the concentration-time curve (AUC) was approximately 2-fold higher for the CLD-CDDP group. Urine excretion rates, which were considered to be related with nephrotoxicities, were significantly lower for the CLD-CDDP. Anti-tumor effect of CDDP has been reported to be dependent on the AUC rather than C-max of filterable platinum. Thus, CLD-CDDP dosing may possibly deliver an improved therapeutic index as compared to the usual bolus dosing method, especially for patients with pelvic tumors which eventually involve the urinary tract leading to impaired renal function.