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 Miller, A. A. Articles by Ratain, M. J. Search for Related Content PubMed PubMed Citation Articles by Miller, A. A. Articles by Ratain, M. J. Social Bookmarking                            What's this?

Phase I and Pharmacokinetic Study of Erlotinib for Solid Tumors in Patients With Hepatic or Renal Dysfunction: CALGB 60101

Antonius A. Miller, Daryl J. Murry, Kouros Owzar, Donna R. Hollis, Lionel D. Lewis, Hedy L. Kindler, John L. Marshall, Miguel A. Villalona-Calero, Martin J. Edelman, Raymond J. Hohl, Stuart M. Lichtman, Mark J. Ratain

From the Wake Forest University School of Medicine, Winston-Salem, NC; University of Iowa College of Pharmacy; University of Iowa Hospitals, Iowa City, IA; Department of Biostatistics and Bioinformatics and Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham, NC; Dartmouth Medical School, Lebanon, NH; Cancer and Leukemia Group B; University of Chicago Medical Center, Chicago, IL; Georgetown University Medical Center, Washington, DC; Ohio State University Medical Center, Columbus, OH; University of Maryland Cancer Center, Baltimore, MD; and North Shore–Long Island Jewish Health System, Manhasset, NY

Address reprint requests to Antonius A. Miller, MD, Comprehensive Cancer Center of Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157-1082; e-mail: aamiller{at}wfubmc.edu

Purpose We investigated dose and pharmacokinetics of erlotinib in patients with hepatic dysfunction or renal dysfunction.

Patients and Methods Patients were assigned to one of three cohorts: cohort 1, AST 3x upper limit of normal; cohort 2, direct bilirubin of 1 to 7 mg/dL; and cohort 3, creatinine of 1.6 to 5.0 mg/dL. Cohort 1a was amended for albumin less than 2.5 g/dL. Erlotinib was administered orally daily to groups of at least three assessable patients in escalating doses of 50, 75, 100, and 150 mg, starting with 50 mg in hepatic dysfunction patients and 75 mg in renal dysfunction patients.

Results Between December 2001 and May 2005, 55 patients were accrued. The distribution of assessable patients was: two of three in cohort 1, three of three in cohort 1a, 16 of 30 in cohort 2, and 18 of 18 in cohort 3. Dose-limiting toxicity (DLT) consisted of elevation of both total and direct bilirubin 1.5x baseline in three patients (cohort 1: one of five patients at 50 mg; cohort 2: two of six patients at 100 mg). In cohort 2, one of seven patients had DLT at 75 mg. No DLT was encountered in cohort 3 with 12 patients at 150 mg. Apparent oral clearance (mean ± standard deviation) was cohort dependent as follows: 1.9 ± 0.2 L/h in cohort 1; 3.7 ± 4.7 L/h in cohort 1a; 2.4 ± 1.1 L/h in cohort 2; and 4.5 ± 2.7 L/h in cohort 3 (Kruskal-Wallis, P < .017).

Conclusion Patients with renal dysfunction tolerate 150 mg of erlotinib daily and seem to have an erlotinib clearance similar to patients without organ dysfunction. Patients with hepatic dysfunction should be treated at a reduced dose (ie, 75 mg daily) consistent with their reduced clearance.

Supported by National Cancer Institute Grants No. CA 03927, CA 47642, CA 33601, CA 47577, CA 04326, CA 41287, CA 77597, CA 77658, CA 31983, CA 47642, CA 35279, and CA 31946.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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

This article has been cited by other articles:

				A. A. Miller, D. J. Murry, K. Owzar, D. R. Hollis, E. B. Kennedy, G. Abou-Alfa, A. Desai, J. Hwang, M. A. Villalona-Calero, E. C. Dees, et al. Phase I and Pharmacokinetic Study of Sorafenib in Patients With Hepatic or Renal Dysfunction: CALGB 60301 J. Clin. Oncol., April 10, 2009; 27(11): 1800 - 1805. [Abstract] [Full Text] [PDF]