Clinical Cancer Research, Vol 2, Issue 3 549-552, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Evaluation of carboplatin pharmacokinetics in the absence and presence of paclitaxel

CK Obasaju, SW Johnson, A Rogatko, D Kilpatrick, JM Brennan, TC Hamilton, RF Ozols, PJ O'Dwyer and JM Gallo
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

In a clinical trial of paclitaxel (Taxol) and carboplatin in combination, the severity of thrombocytopenia was less than would be expected with an equivalent dose of carboplatin alone. To determine whether a pharmacokinetic interaction was responsible for this observation, the effect of pretreatment with Taxol on the pharmacokinetics of carboplatin was examined in 11 patients. Each patient was randomized to one of two treatment groups that determined the order of drug treatments. The treatments were carboplatin as a 30-min infusion alone or immediately following 175 mg/m2 Taxol administered as a 3-h i.v. infusion. The treatments were separated by 1 week. The carboplatin dose was chosen to produce a target area under the concentration-time curve (AUC) of 3.75 mg-min/ml according to a previously published formula (A. H. Calvert et al., J. Clin Oncol., 7: 1748-1756, 1989). The mean administered dose of carboplatin was 338 mg. Serial blood samples were collected over 24 h and analyzed for total and free platinum, and, in some patients, Taxol. The pharmacokinetics of carboplatin (i.e., total clearance and volume of distribution at steady state), was not significantly affected by pretreatment with Taxol. Total clearances of carboplatin were 67.2 +/- 28.8 ml/min and 64.6 +/- 27.9 ml/min in the absence and presence of Taxol, respectively (P = 0.56). The AUC of free carboplatin (3.45 mg-min/ml) obtained in the absence of Taxol was not significantly different from that measured in the presence of Taxol (3.27 mg-min/ml). The AUC of carboplatin in both the absence and presence of Taxol agreed with the projected target AUC of 3.75 mg-min/ml. In conclusion, the application of an individualized dosing strategy is valid for the calculation of the carboplatin dose in this combination. The pharmacokinetics of carboplatin is not altered by pretreatment with Taxol at a standard dose, and a pharmacokinetic interaction is not responsible for the altered toxicity of the combination.

This article has been cited by other articles:

				S. Kaestner and G. Sewell Dose-banding of carboplatin: rationale and proposed banding scheme Journal of Oncology Pharmacy Practice, June 1, 2007; 13(2): 109 - 117. [Abstract] [PDF]

				S. Kaestner and G. Sewell A sequential temperature cycling study for the investigation of carboplatin infusion stability to facilitate `dose-banding' Journal of Oncology Pharmacy Practice, June 1, 2007; 13(2): 119 - 126. [Abstract] [PDF]

				M. Nakajima, Y. Fujiki, S. Kyo, T. Kanaya, M. Nakamura, Y. Maida, M. Tanaka, M. Inoue, and T. Yokoi Pharmacokinetics of Paclitaxel in Ovarian Cancer Patients and Genetic Polymorphisms of CYP2C8, CYP3A4, and MDR1 J. Clin. Pharmacol., June 1, 2005; 45(6): 674 - 682. [Abstract] [Full Text] [PDF]

				M. B. Polee, A. Sparreboom, F. A. L. M. Eskens, R. Hoekstra, J. van de Schaaf, J. Verweij, G. Stoter, and A. van der Gaast A Phase I and Pharmacokinetic Study of Weekly Paclitaxel and Carboplatin in Patients with Metastatic Esophageal Cancer Clin. Cancer Res., March 15, 2004; 10(6): 1928 - 1934. [Abstract] [Full Text] [PDF]

				W. K. Kelly, A. X. Zhu, H. Scher, T. Curley, M. Fallon, S. Slovin, L. Schwartz, S. Larson, W. Tong, B. Hartley-Asp, et al. Dose Escalation Study of Intravenous Estramustine Phosphate in Combination with Paclitaxel and Carboplatin in Patients with Advanced Prostate Cancer Clin. Cancer Res., June 1, 2003; 9(6): 2098 - 2107. [Abstract] [Full Text] [PDF]

				R. J. Schilder, J. M. Gallo, M. M. Millenson, M. A. Bookman, L. M. Weiner, A. Rogatko, B. Rogers, K. Padavic-Shallers, M. Boente, N. Rosenblum, et al. Phase I Trial of Multiple Cycles of High-Dose Carboplatin, Paclitaxel, and Topotecan With Peripheral-Blood Stem-Cell Support as Front-Line Therapy J. Clin. Oncol., February 15, 2001; 19(4): 1183 - 1194. [Abstract] [Full Text] [PDF]

				W. K. Kelly, T. Curley, S. Slovin, G. Heller, J. McCaffrey, D. Bajorin, A. Ciolino, K. Regan, M. Schwartz, P. Kantoff, et al. Paclitaxel, Estramustine Phosphate, and Carboplatin in Patients With Advanced Prostate Cancer J. Clin. Oncol., January 1, 2001; 19(1): 44 - 53. [Abstract] [Full Text] [PDF]

				M. Ando, H. Minami, Y. Ando, H. Saka, S. Sakai, M. Yamamoto, Y. Sasaki, K. Shimokata, and Y. Hasegawa Multi-Institutional Validation Study of Carboplatin Dosing Formula Using Adjusted Serum Creatinine Level Clin. Cancer Res., December 1, 2000; 6(12): 4733 - 4738. [Abstract] [Full Text]