Journal of the National Cancer Institute Advance Access originally published online on June 12, 2007
JNCI Journal of the National Cancer Institute 2007 99(12):976-977; doi:10.1093/jnci/djm009
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© The Author 2007. Published by Oxford University Press.
CORRESPONDENCE |
Response: Re: Hypothyroidism in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib
Correspondence to: Brian I. Rini, MD, Department of Solid Tumor Oncology and Urology, Cleveland Clinic Taussig Cancer Center, 9500 Euclid Ave, Desk R35, Cleveland, OH 44195 (e-mail: rinib2{at}ccf.org).
We appreciate the interest of Feldman et al. and of Garfield et al. in our recent publication regarding thyroid function test (TFT) abnormalities in metastatic renal cell carcinoma (RCC) patients receiving sunitinib (1). The important conclusion is that hypothyroidism is commonly observed with sunitinib therapy and necessitates routine monitoring. Thyroid hormone replacement is easily administered in such patients when clinically indicated, and this phenomenon does not adversely impact the utility of sunitinib in metastatic RCC.
As noted, some patients in our cohort had elevated levels of thyroid-stimulating hormone (TSH) at baseline. Seven (19%) of the 37 patients in our series with available baseline TFTs had an elevated TSH, although the majority were mild, not associated with other TFT abnormalities or clinical symptoms, and did not require hormone replacement. Feldman et al. cite a baseline hypothyroidism prevalence of 4%–8% in an adult population from a recent review (2). This review also states that the prevalence of subclinical hypothyroidism increases with age up to as high as 20%, consistent with our experience and that of others (3). Indeed, other series have noted that the incidence of thyroid dysfunction may be higher in RCC patients than in the general population (4). There were two patients on thyroid hormone therapy at the start of sunitinib therapy in our report. The TSH of such patients rose on sunitinib, requiring a modest increase in their synthroid dose to maintain a clinically euthyroid state.
The retrospective reports of sunitinib-induced hypothyroidism which are currently available are likely to overestimate (if any biochemical TFT abnormality is considered) or underestimate (if only symptomatic patients are tested) the true incidence of thyroid dysfunction. As such, ongoing prospective trials will more fully define the treatment-induced incidence of this toxicity and, hopefully, elucidate the most appropriate management strategy and mechanism(s) underlying this phenomenon. Such studies can also accurately define the true incidence of thyroid abnormalities at baseline in this population of patients and determine whether baseline or posttreatment abnormalities are associated with any consequences relative to clinical outcome. Although TFT abnormalities are not always of clinical importance, Feldman et al. correctly state that the metabolic and other adverse effects can be severe if untreated. We also do not advocate reflexive thyroid hormone replacement for biochemical abnormalities alone. As with any population, clinical judgment as to the necessity and timing of replacement therapy must be exercised. Garfield et al. cite several references with indirect evidence that hypothyroidism can affect clinical outcome to cancer therapy. Although interesting, not all reports support these observations, and such an association may or may not hold for metastatic RCC patients and sunitinib therapy. As noted above, prospective testing of this hypothesis is needed. The demonstration of survival benefit to sorafenib in hepatocellular carcinoma is in no way a demonstration of an association between treatment-induced hypothyroidism and improved clinical outcome. There is, therefore, a need for monitoring, recognition, and treatment of thyroid dysfunction in metastatic RCC patients receiving sunitinib.
REFERENCES
(1) Rini BI, Tamaskar I, Shaheen P, Salas R, Garcia J, Wood L, et al. Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst (2007) 99:81–3.
(2) Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA (2004) 291:228–38.
(3) Desai J, Yassa L, Marqusee E, George S, Frates MC, Chen MH, et al. Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med (2006) 145:660–4.
(4) Rosenberg AG, Dexeus F, Swanson DA, von Eschenbach AC. Relationship of thyroid disease to renal cell carcinoma. An epidemiologic study. Urology (1990) 35:492–8.[CrossRef][Web of Science][Medline]
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Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 974-975.
J Natl Cancer Inst 2007 99: 975-976.
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