This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Itoh, K. Articles by Ohashi, Y. Search for Related Content PubMed PubMed Citation Articles by Itoh, K. Articles by Ohashi, Y.

Study of Dose Escalation and Sequence Switching of Administration of the Combination of Docetaxel and Doxorubicin in Advanced Breast Cancer

Division of Oncology and Hematology, National Cancer Center Hospital East, Kashiwa 277-8577 [K. I., Y. S., H. F., H. M., T. O., H. W., T. I., Y. W., Y. On.]; Rhône-Poulenc Rorer Japan, Inc., Ibaraki 315 [M. K.]; and Epidemiology and Biostatistics, School of Health Sciences and Nursing, Faculty of Medicine, University of Tokyo, Tokyo 113-0033 [Y. Oh.], Japan

The objectives of the present study were to evaluate whether a schedule-dependent pharmacokinetic and/or pharmacodynamic interaction exists between two sequences of docetaxel and doxorubicin administration and to determine the maximal tolerated dose (MTD) of this combination. Patients with chemotherapy-naïve metastatic or recurrent advanced breast cancer were enrolled. In the crossover design, tandem dose escalation of docetaxel and doxorubicin was performed. Docetaxel, in doses ranging from 50–70 mg/m², was administered for 1 h by drip infusion either just before or after a 5-min bolus i.v. injection of doxorubicin at dosages from 40–50 mg/m². The sequence of drug administration was switched after the first course in each patient, and the sequence of drug administration thereafter depended on the patient’s choice. Twenty-five patients were initially assessable for toxicity. The MTD in the sequence of doxorubicin after docetaxel was 40 and 50 mg/m², respectively, with the dose-limiting toxicity of neutropenia. On the other hand, the MTD of the sequence of docetaxel after doxorubicin was 70 and 50 mg/m², respectively. The dose-limiting toxicities in this sequence were neutropenia and diarrhea. Duration of grade 4 neutropenia in the sequence of docetaxel followed by doxorubicin was significantly longer than that in the alternate sequence (P = 0.0062). However, there was no difference in pharmacokinetic parameters of docetaxel, doxorubicin, and doxorubicinol between the two sequences. The sequence of 50 mg/m² doxorubicin followed by 60 mg/m² docetaxel is recommended for subsequent clinical trials for practical reasons.

This article has been cited by other articles:

				M. Tabuchi, H. To, H. Sakaguchi, N. Goto, A. Takeuchi, S. Higuchi, and S. Ohdo Therapeutic Index by Combination of Adriamycin and Docetaxel Depends on Dosing Time in Mice Cancer Res., September 15, 2005; 65(18): 8448 - 8454. [Abstract] [Full Text] [PDF]

				S. Cresta, G. Grasselli, M. Mansutti, A. Martoni, G. Lelli, G. Capri, F. Buzzi, G. Robustelli Della Cuna, A. Jirillo, E. Terzoli, et al. A randomized phase II study of combination, alternating and sequential regimens of doxorubicin and docetaxel as first-line chemotherapy for women with metastatic breast cancer Ann. Onc., March 1, 2004; 15(3): 433 - 439. [Abstract] [Full Text] [PDF]

				G. Lunardi, M. Venturini, M. O. Vannozzi, G. Tolino, L. Del Mastro, C. Bighin, G. Schettini, and M. Esposito Influence of alternate sequences of epirubicin and docetaxel on the pharmacokinetic behaviour of both drugs in advanced breast cancer Ann. Onc., February 20, 2002; 13(2): 280 - 285. [Abstract] [Full Text] [PDF]