Originally published as JCO Early Release 10.1200/JCO.2008.19.0645 on September 29 2008

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In Reply

Harold J. Burstein

Dana-Farber Cancer Institute, Boston, MA

Kathy D. Miller

Indiana University, Indianapolis, IN

Mark A. Socinski

University of North Carolina, Chapel Hill, NC

Leonard B. Saltz

Memorial Sloan-Kettering Cancer Center, New York, NY

Thyroid test abnormalities and clinical thyroid illness have been reported in association with several tyrosine kinase inhibitors, including sunitinib,^1-3 imatinib,⁴ and sorafenib.⁵ Results from the largest clinical series to date suggest that 53% to 85% of oncology patients treated with sunitinib develop thyroid test abnormalities, and a substantial percentage develop clinical manifestations of thyroid dysfunction.^1,2 Garfield et al have in previous correspondence raised important questions about the prevalence of thyroid dysfunction and the relationship of hypothyroidism to clinical outcomes in cancer patients receiving sunitinib.^6,7 Because the relationship of thyroid dysfunction and sunitinib was not well appreciated when the protocols were written, none of the three disease-specific phase II trials in colorectal, non–small-cell lung, or breast cancer prospectively collected laboratory data on thyroid function. Thus, neither the incidence nor the relationship to treatment effects can be known. Investigator-initiated adverse event reports have documented grade 1 or 2 thyroid dysfunction in less than 5% of patients on these trials, and no grade 3 or 4 toxicity was observed. However, the nature of the reporting and the complexities of assessing fatigue in cancer patients likely underestimated the clinical incidence of thyroid disease in cancer patients receiving sunitinib therapy. Studies to assess the clinical impact of sunitinib therapy on thyroid function are ongoing.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: Leonard B. Saltz, Pfizer (C) Stock Ownership: None Honoraria: None Research Funding: Kathy D. Miller, Pfizer; Mark A. Socinski, Pfizer; Leonard B. Saltz, Pfizer Expert Testimony: None Other Remuneration: None

NOTES

published online ahead of print at www.jco.org on September 29, 2008, 2007

REFERENCES

1. Desai J, Yassa L, Marqusee E, et al: Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med 145:660-664, 2006[Abstract/Free Full Text]

2. Rini BI, Tamaskar I, Shaheen P, et al: Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst 99:81-83, 2007[Abstract/Free Full Text]

3. Wong E, Rosen LS, Mulay M, et al: Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid 17:351-355, 2007[CrossRef][Medline]

4. de Grott JWB, Links TP, van der Graaf WTA: Tyrosine kinase inhibitors causing hypothyroidism in a patient on levothyroxine. Ann Oncol 17:1719-1720, 2006[Free Full Text]

5. Tamaskar I, Bukowski R, Elson P, et al: Thyroid function test abnormalities in patients with metastatic renal cell carcinoma treated with sorafenib. Ann Oncol 19:265-268, 2008[Abstract/Free Full Text]

6. Wolter P, Dumez H, Schoffski P: Sunitinib and hypothyroidism. N Engl J Med 356:1580, 2007[Free Full Text]

7. Garfield D, Hercbergs A, Davis P: Unanswered questions regarding the management of sunitinib-induced hypothyroidism. Nat Clin Pract Oncol 4:674, 2007[CrossRef][Medline]

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This Article 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 Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Burstein, H. J. Articles by Saltz, L. B. Search for Related Content PubMed Articles by Burstein, H. J. Articles by Saltz, L. B. Related Articles Related Correspondence Social Bookmarking                            What's this?