This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Adjei, A. A. Articles by Erlichman, C. Search for Related Content PubMed PubMed Citation Articles by Adjei, A. A. Articles by Erlichman, C. Social Bookmarking                            What's this?

Phase I and Pharmacokinetic Study of Irinotecan and Docetaxel in Patients With Advanced Solid Tumors: Preliminary Evidence of Clinical Activity

From the Department of Oncology, Mayo Clinic and Foundation, Rochester, MN, and Department of Pharmaceutics and Pharmacodynamics, College of Pharmacy, University of Illinois, Chicago, IL.

Address reprint requests to Alex A. Adjei, MD, PhD, Division of Medical Oncology, Mayo Clinic, 200 First St, SW, Rochester, MN 55905; email adjei.alex{at}mayo.edu

PURPOSE: The goals of this study were to determine the maximum-tolerated dose and describe the toxicities of the combination of irinotecan and docetaxel administered every 3 weeks to patients with advanced malignancies and, also, to evaluate the effect of irinotecan on the disposition of docetaxel and describe preliminary evidence of antitumor activity.

PATIENTS AND METHODS: Eighteen patients received 85 courses (median, two courses; range, one to 15 courses) of treatment with irinotecan, administered over 90 minutes by intravenous infusion, followed by docetaxel, administered over 60 minutes by intravenous infusion. Four escalating dose levels of irinotecan/docetaxel (160/50 mg/m², 160/65 mg/m², 200/65 mg/m², and 200/75 mg/m²) were studied. Pharmacokinetic analyses were performed to evaluate the effect of irinotecan on the disposition of docetaxel.

RESULTS: The most common and dose-limiting toxicity was myelosuppression, which consisted of neutropenia that was severe (National Cancer Institute common toxicity criteria [NCI CTC] grade 4) but brief (< 5 days) in 11 patients, with three episodes of febrile neutropenia. Nonhematologic toxicities of anorexia, nausea, and stomatitis were mild to moderate (NCI CTC grades 1 and 2), but there was one incidence each of both CTC grade 3 anorexia and nausea. All patients had total alopecia. Diarrhea was dose-dependent and severe in four patients who failed to take adequate antidiarrhea therapy. Five out of 16 assessable patients, one with cholangiocarcinoma, one with leiomyosarcoma, and three with non–small-cell lung cancer, achieved partial remissions.

CONCLUSION: The combination of irinotecan and docetaxel causes significant reversible myelosuppression, which was dose limiting but led to no serious sequelae. There was no evidence of a clinically significant interaction using these two agents in this sequence. The combination showed antitumor activity at all the dose levels tested and should be further studied in a number of tumor types. The recommended phase II dose on this schedule is irinotecan 160 mg/m² and docetaxel 65 mg/m².

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				W. W. Tan, D. W. Hillman, M. Salim, D. W. Northfelt, D. M. Anderson, P. J. Stella, R. Niedringhaus, A. M. Bernath, S. S. Gamini, F. Palmieri, et al. N0332 phase 2 trial of weekly irinotecan hydrochloride and docetaxel in refractory metastatic breast cancer: a North Central Cancer Treatment Group (NCCTG) Trial Ann. Onc., July 22, 2009; (2009) mdp328v1. [Abstract] [Full Text] [PDF]

				B. Burtness, M. Gibson, B. Egleston, R. Mehra, L. Thomas, R. Sipples, M. Quintanilla, J. Lacy, S. Watkins, J. R. Murren, et al. Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer Ann. Onc., July 1, 2009; 20(7): 1242 - 1248. [Abstract] [Full Text] [PDF]

				M. A. Lee, I. S. Woo, J.-H. Kang, Y. S. Hong, and K. S. Lee Gemcitabine and Cisplatin Combination Chemotherapy in Intrahepatic Cholangiocarcinoma as Second-line Treatment: Report of Four Cases Jpn. J. Clin. Oncol., September 1, 2004; 34(9): 547 - 550. [Abstract] [Full Text] [PDF]

				S. D. Baker, M. Zhao, C. K. K. Lee, J. Verweij, Y. Zabelina, J. R. Brahmer, A. C. Wolff, A. Sparreboom, and M. A. Carducci Comparative Pharmacokinetics of Weekly and Every-Three-Weeks Docetaxel Clin. Cancer Res., March 15, 2004; 10(6): 1976 - 1983. [Abstract] [Full Text] [PDF]

				R. H. J. Mathijssen, R. J. van Alphen, J. Verweij, W. J. Loos, K. Nooter, G. Stoter, and A. Sparreboom Clinical Pharmacokinetics and Metabolism of Irinotecan (CPT-11) Clin. Cancer Res., August 1, 2001; 7(8): 2182 - 2194. [Abstract] [Full Text] [PDF]