| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author 2007. Published by Oxford University Press.
BRIEF COMMUNICATION |
Hypothyroidism in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib
Affiliations of authors: Department of Solid Tumor Oncology, Taussig Cancer Center (BIR, IT, PS, RS, JG, LW, RD, RMB), and Department of Endocrinology, Diabetes, and Metabolism (SR), Cleveland Clinic, Cleveland, OH
Correspondence to: Brian I. Rini, MD, Departments of Solid Tumor Oncology and Urology, Taussig Cancer Center, Cleveland Clinic, 9500 Euclid Ave., Desk R35, Cleveland, OH 44195 (e-mail: rinib2{at}ccf.org).
 |
ABSTRACT |
|---|
 TopNotes Abstract Context and CaveatsReferences |
|---|
Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted.
Prior knowledge Fatigue was the most common toxic effect in patients with metastatic renal cell carcinoma in trials of sunitinib. Thyroid dysfunction has been associated with anticancer treatment for renal cell carcinoma. Study type Single clinic–based case series. Contribution Sunitinib treatment of patients with metastatic renal cell carcinoma can cause biochemical and clinical thyroid dysfunction. Symptoms improved in some patients after thyroid hormone replacement therapy. Implications Thyroid function test abnormalities are common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring may be of value. Limitations The number of patients was small and there were no control subjects, so it could not be determined whether thyroid dysfunction was associated with outcome.
|
Sunitinib, an orally bioavailable oxindole, is small-molecule tyrosine kinase inhibitor for vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptors (1,2). The antitumor activity of this agent was initially established in two, sequential single-arm phase II trials in patients with cytokine-refractory metastatic renal cell carcinoma. Objective response rates to sunitinib of approximately 40% and progression-free survival of 8.2 months were observed in these trials (3,4). A subsequent, randomized phase III trial in untreated patients with metastatic renal cell carcinoma that compared sunitinib with interferon 
observed a statistically significantly increased objective response rate (31% versus 6%, respectively; P<.001, Pearson chi-square test) and progression-free survival (11 months versus 5 months, respectively; P<.001, unstratified log-rank test) (5). In addition, activity of sunitinib against imatinib-resistant gastrointestinal stromal tumors led the Food and Drug Administration to approve sunitinib for treatment of imatinib-refractory gastrointestinal stromal tumor and advanced renal cell carcinoma in January 2006 (6).
Common toxic effects in the renal cell carcinoma trials of sunitinib included fatigue, diarrhea, hand/foot syndrome, stomatitis, and hypertension. Fatigue was the most common and was often the dose-limiting toxicity of sunitinib in patients with metastatic renal cell carcinoma. Fatigue in these patients prompted us to measure their thyroid function. In this report, we summarize the investigation of biochemical and clinical thyroid abnormalities in a cohort of patients with metastatic renal cell carcinoma treated with sunitinib. All patients, regardless of sex, were analyzed as a single cohort.
The medical records of patients with metastatic renal cell carcinoma enrolled in one of four institutional review board–approved clinical trials of sunitinib monotherapy were reviewed. All patients signed a written informed consent form that was approved by the institutional review board. All patients received 50 mg of sunitinib orally daily for the first 28 days of a 42-day cycle, with dose adjustment to 37.5 or 25 mg daily for toxicity, as required. Thyroid function test assessment (i.e., thyroid-stimulating hormone, T3, and T4 levels and free thyroxine index) was undertaken initially on some patients because the treating physicians suspected thyroid dysfunction and later on all patients prospectively. Thyroid hormone replacement therapy and/or more frequent thyroid function testing were undertaken at the discretion of the treating physician. The frequency and results of thyroid function tests and any signs or symptoms of thyroid dysfunction were collected. An objective response, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, was recorded for all patients (7).
Between May 1, 2004, and March 31, 2006, 73 patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center. The demographic characteristics of all patients treated are presented in Table 1. Sixty-six patients had thyroid function test results available, initially obtained because of the clinical suspicion of treating physicians (n = 29) and later prospectively as routine laboratory assessment performed at baseline and on day 28 of every even-numbered cycle (n = 37). All patients with thyroid function test results had metastatic renal cell carcinoma. Patients in this study were treatment naive (n = 30) or had been treated with cytokine-based therapy (n = 30) or bevacizumab (Avastin, Genentech, South San Francisco, CA)-based therapy (n = 6) and then relapsed, as required by the eligibility criteria for the clinical trials in which they participated.
|
Table 2 presents the thyroid function characteristics of the patients with metastatic renal cell carcinoma who were receiving sunitinib. Median thyroid-stimulating hormone at baseline was 2.56 mIU/L (range = 0.8–34.8; a normal range is 0.40–5.50 mIU/mL). Fifty-six (85%; 95% confidence interval (CI) = 74% to 92%) of the 66 patients with test results had one or more thyroid function test abnormalities. Such abnormalities were consistent with hypothyroidism in all patients and primarily included elevation of thyroid-stimulating hormone and decreased levels of T3 and, less commonly, decreases in T4 and/or of the free thyroxine index. Thyroid function test abnormalities were detected relatively early in the treatment course (median = at cycle 2), with a broad range. There were 43 males and 13 females with abnormal thyroid function test results, with a median age of 58 years (range = 23–72 years). The demographics and disease characteristics of patients with thyroid function test abnormalities were similar to those patients without such abnormalities. Two patients had a history of well-controlled hypothyroidism before the initiation of sunitinib treatment. The thyroid function tests of these two patients were consistent with more severe hypothyroidism during therapy with sunitinib. Among patients with abnormal thyroid function tests, signs and symptoms possibly related to hypothyroidism were found in 47 patients (84%; 95% CI = 72% to 92%), including fatigue, cold intolerance, anorexia, periorbital edema, fluid retention, and changes in skin or hair. Thyroid hormone replacement was undertaken at the discretion of the treating physician (on the basis of the degree of biochemical abnormality and/or clinical symptoms) in 17 patients (30% of those with abnormal thyroid function tests, 95% CI = 19% to 44%) and resulted in resolution of biochemical abnormalities in all patients and improved symptoms in nine patients. Thyroglobulin antibodies were measured in 44 patients and were abnormal (i.e., >10.0 IU/mL) in 13 patients (30%, 95% CI = 17% to 45%; eight patients at baseline and five patients after treatment). There was no association between the presence of thyroglobulin autoantibodies and either the incidence or severity of thyroid function test abnormalities. No other thyroid autoantibodies were measured. Among the 56 patients with abnormal thyroid function test results, 55 had tumor evaluation results available. The best response as defined by RECIST criteria was partial or complete response in 26 patients (47%, 95% CI = 34% to 61%). Among the 29 patients who did not achieve an objective response, 25 (44%) had stable disease and 4 (7%) had progressive disease.
|
In vitro and in vivo studies (8–10) have found the expression of VEGF and VEGF receptor mRNA and protein in normal thyroid follicular cells, mediated at least in part by thyroid-stimulating hormone. Expression of VEGF protein and its receptor has not been well characterized in human thyroid tissue, and the dependence upon VEGF for normal thyroid function is unknown. It is possible that sunitinib, a VEGF receptor inhibitor, decreases thyroid function by preventing binding of VEGF to normal thyroid cells and/or by impairing thyroid blood flow, which results in thyroiditis. This hypothesis requires prospective testing and further examination of normal thyroid tissue in a cancer population. Sunitinib-induced hypothyroidism does not appear to be specific to patients with renal cell carcinoma because prior reports (11,12) in patients with gastrointestinal stromal tumor have also noted a substantial number of patients with hypothyroidism.
Anticancer treatment in metastatic renal cell carcinoma has previously been associated with thyroid dysfunction (13–15). Development of thyroid autoantibodies has been associated with improved outcome in patients with metastatic renal cell carcinoma receiving immunotherapy, such as therapy with interleukin 2 or interferon (13,14). Although the mechanism of this potentially enhanced response remains unclear, it may involve a treatment-induced alteration of immune responsiveness and self-tolerance. The association of hypothyroidism without autoantibodies and improved clinical outcome in patients with metastatic renal cell carcinoma receiving cytokines has been observed in some, but not all, studies (15,16). The objective response rates observed in patients with thyroid dysfunction in the present series approximate those observed in the general experience among sunitinib-treated patients with metastatic renal cell carcinoma. Thus, it cannot be determined from this small series of patients whether thyroid dysfunction is associated with clinical outcome in patients with metastatic renal cell carcinoma receiving sunitinib. This conclusion is tempered by certain study limitations, including the lack of baseline thyroid function tests in some patients, the relatively small number of total patients, and the high prevalence of biochemical hypothyroidism. Further examination of hypothyroidism, thyroid autoantibodies, and additional clinical outcome measures, such as tumor shrinkage and progression-free survival, are warranted to investigate a possible association.
In conclusion, sunitinib treatment in metastatic renal cell carcinoma patients can cause biochemical and clinical hypothyroidism. Routine monitoring of thyroid function tests is warranted, and replacement therapy should be undertaken as clinically indicated.
|
NOTES |
|---|
|
TopNotesAbstractContext and CaveatsReferences |
|---|
Dr J. Garcia is currently conducting research sponsored by Genentech, Celgene, and Pfizer. He is also a member of the speaker's bureau for Pfizer and Bayer/Onyx. Dr R. M. Bukowski is currently conducting research sponsored by Pfizer and Bayer. He is also a member of the Pfizer speaker's bureau and was a consultant for Pfizer and Bayer. Dr L. Wood is a member of the nursing speaker's bureau for Pfizer. Dr B. I. Rini is a consultant for Pfizer and is currently conducting research funded by Pfizer.
Patients reported here participated in clinical trials funded in part by Pfizer, Inc, and Pfizer was involved in design, data collection, analysis, and interpretation of the clinical results of those trials. Pfizer, Inc, did not have any role in the design, analysis, decision to submit, or manuscript preparation of the thyroid function data reported in this study. The authors had full responsibility for these activities.
Presented in part at the American Society of Clinical Oncology Annual Meeting 2006.
|
REFERENCES |
|---|
|
TopNotesAbstractContext and CaveatsReferences |
|---|
(1) Sun L, Liang C, Shirazian S, Zhou Y, Miller T, Cui J, et al. Discovery of 5-[5-fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2, 4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J Med Chem 2003;46:1116–9.[CrossRef][Web of Science][Medline]
(2) Mendel DB, Laird AD, Xin X, Louie SG, Christensen JG, Li G, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9:327–37.
(3) Motzer RJ, Michaelson MD, Redman BG, Hudes GR, Wilding G, Figlin RA, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:16–24.
(4) Motzer RJ, Rini BI, Bukowski RM, Curti BD, George DJ, Hudes GR, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 2006;295:2516–24.
(5) Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe R, et al. Phase III randomized trial of sunitinib malate (SU11248) versus interferon-alfa (IFN-) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC). 2006 American Society of Clinical Oncology Annual Meeting Proceedings Pt I. Vol 24 (June 20 Suppl); 2006: LBA3.
(6) Demitri GD, van Oosterom AT, Blackstein M, Garrett C, Shah M, Heinrich M, et al. Phase 3, multicenter, randomized, double-blind, placebo-controlled trial of SU11248 in patients (pts) following failure of imatinib for metastatic GIST. 2005 American Society of Clinical Oncology Annual Meeting Proceedings Pt I of II. Vol 23 (June 1 Suppl); 2005:4000.
(7) Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–16.
(8) Ramsden JD. Angiogenesis in the thyroid gland. J Endocrinol 2000;166:475–80.[Abstract]
(9) Viglietto G, Romano A, Manzo G, Chiappetta G, Paoletti I, Califano D, et al. Upregulation of the angiogenic factors PlGF, VEGF and their receptors (Flt-1, Flk-1/KDR) by TSH in cultured thyrocytes and in the thyroid gland of thiouracil-fed rats suggest a TSH-dependent paracrine mechanism for goiter hypervascularization. Oncogene 1997;15:2687–98.[CrossRef][Web of Science][Medline]
(10) Wang JF, Milosveski V, Schramek C, Fong GH, Becks GP, Hill DJ. Presence and possible role of vascular endothelial growth factor in thyroid cell growth and function. J Endocrinol 1998;157:5–12.[Abstract]
(11) Schoeffski P, Wolter P, Himpe U, Dychter SS, Baum CM, Prenen H, et al. Sunitinib-related thyroid dysfunction: a single-center retrospective and prospective evaluation. J Clin Oncol 2006;24:3092.
(12) 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.
(13) Atkins MB, Mier JW, Parkinson DR, Gould JA, Berkman EM, Kaplan MM. Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. N Engl J Med 1988;318:1557–63.[Abstract]
(14) Franzke A, Peest D, Probst-Kepper M, Buer J, Kirchner GI, Brabant G, et al. Autoimmunity resulting from cytokine treatment predicts long-term survival in patients with metastatic renal cell cancer. J Clin Oncol 1999;17:529–33.
(15) Weijl NI, Van der Harst D, Brand A, Kooy Y, Van Luxemburg S, Schroder J, et al. Hypothyroidism during immunotherapy with interleukin-2 is associated with antithyroid antibodies and response to treatment. J Clin Oncol 1993;11:1376–83.
(16) Krouse RS, Royal RE, Heywood G, Weintraub BD, White DE, Steinberg SM, et al. Thyroid dysfunction in 281 patients with metastatic melanoma or renal carcinoma treated with interleukin-2 alone. J Immunother Emphasis Tumor Immunol 1995;18:272–8.[Medline]
Manuscript received July 14, 2006; revised October 17, 2006; accepted October 24, 2006.
Correspondence about this Article
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 975-976.
This article has been cited by other articles:
|
|
 |
|
  T. B. Dorff, A. Goldkorn, and D. I. Quinn Review: Targeted therapy in renal cancer Therapeutic Advances in Medical Oncology, November 1, 2009; 1(3): 183 - 205. [Abstract] [PDF]
|
|
|
|
 |
|
 B. I. Rini, J. A. Garcia, M. M. Cooney, P. Elson, A. Tyler, K. Beatty, J. Bokar, T. Mekhail, R.M. Bukowski, G. T. Budd, et al. A Phase I Study of Sunitinib plus Bevacizumab in Advanced Solid Tumors Clin. Cancer Res., October 1, 2009; 15(19): 6277 - 6283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Cersosimo Renal cell carcinoma with an emphasis on drug therapy of advanced disease, part 2 Am. J. Health Syst. Pharm., September 15, 2009; 66(18): 1625 - 1633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Demetri, M. C. Heinrich, J. A. Fletcher, C. D.M. Fletcher, A. D. Van den Abbeele, C. L. Corless, C. R. Antonescu, S. George, J. A. Morgan, M. H. Chen, et al. Molecular Target Modulation, Imaging, and Clinical Evaluation of Gastrointestinal Stromal Tumor Patients Treated with Sunitinib Malate after Imatinib Failure Clin. Cancer Res., September 15, 2009; 15(18): 5902 - 5909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. van Erp, K. Eechoute, A. A. van der Veldt, J. B. Haanen, A. K.L. Reyners, R. H.J. Mathijssen, E. Boven, T. van der Straaten, R. F. Baak-Pablo, J. A.M. Wessels, et al. Pharmacogenetic Pathway Analysis for Determination of Sunitinib-Induced Toxicity J. Clin. Oncol., September 10, 2009; 27(26): 4406 - 4412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A.L.M. Eskens, N. Steeghs, J. Verweij, J. L. Bloem, O. Christensen, L. van Doorn, J. Ouwerkerk, M. J.A. de Jonge, J. W.R. Nortier, J. Kraetzschmar, et al. Phase I Dose Escalation Study of Telatinib, a Tyrosine Kinase Inhibitor of Vascular Endothelial Growth Factor Receptor 2 and 3, Platelet-Derived Growth Factor Receptor {beta}, and c-Kit, in Patients With Advanced or Metastatic Solid Tumors J. Clin. Oncol., September 1, 2009; 27(25): 4169 - 4176. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Blay Pharmacological management of gastrointestinal stromal tumours: an update on the role of sunitinib Ann. Onc., August 12, 2009; (2009) mdp291v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Schiller, T. Larson, S.-H. I. Ou, S. Limentani, A. Sandler, E. Vokes, S. Kim, K. Liau, P. Bycott, A. J. Olszanski, et al. Efficacy and Safety of Axitinib in Patients With Advanced Non-Small-Cell Lung Cancer: Results From a Phase II Study J. Clin. Oncol., August 10, 2009; 27(23): 3836 - 3841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Motzer, T. E. Hutson, P. Tomczak, M. D. Michaelson, R. M. Bukowski, S. Oudard, S. Negrier, C. Szczylik, R. Pili, G. A. Bjarnason, et al. Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma J. Clin. Oncol., August 1, 2009; 27(22): 3584 - 3590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Rini Metastatic Renal Cell Carcinoma: Many Treatment Options, One Patient J. Clin. Oncol., July 1, 2009; 27(19): 3225 - 3234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ravaud How to optimise treatment compliance in metastatic renal cell carcinoma with targeted agents Ann. Onc., May 1, 2009; 20(suppl_1): i7 - i12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Iglesias and J J Diez Thyroid dysfunction and kidney disease Eur. J. Endocrinol., April 1, 2009; 160(4): 503 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M Weise, C. Y Liu, and A. F Shields Fatal Liver Failure in a Patient on Acetaminophen Treated with Sunitinib Malate and Levothyroxine Ann. Pharmacother., April 1, 2009; 43(4): 761 - 766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Illouz, S. Laboureau-Soares, S. Dubois, V. Rohmer, and P. Rodien Tyrosine kinase inhibitors and modifications of thyroid function tests: a review Eur. J. Endocrinol., March 1, 2009; 160(3): 331 - 336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schmidinger, C. C. Zielinski, U. M. Vogl, A. Bojic, M. Bojic, C. Schukro, M. Ruhsam, M. Hejna, and H. Schmidinger Cardiac Toxicity of Sunitinib and Sorafenib in Patients With Metastatic Renal Cell Carcinoma J. Clin. Oncol., November 10, 2008; 26(32): 5204 - 5212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Garfield, P. Wolter, P. Schoffski, A. Hercbergs, and P. Davis Documentation of Thyroid Function in Clinical Studies With Sunitinib: Why Does It Matter? J. Clin. Oncol., November 1, 2008; 26(31): 5131 - 5132. [Full Text] [PDF]
|
|
|
|
|
|
H. J. Burstein, K. D. Miller, M. A. Socinski, and L. B. Saltz In Reply J. Clin. Oncol., November 1, 2008; 26(31): 5132 - 5133. [Full Text] [PDF]
|
|
|
|
|
|
D. G. Pfister and J. A. Fagin Refractory Thyroid Cancer: A Paradigm Shift in Treatment Is Not Far Off J. Clin. Oncol., October 10, 2008; 26(29): 4701 - 4704. [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Hutson, R. A. Figlin, J. G. Kuhn, and R. J. Motzer Targeted Therapies for Metastatic Renal Cell Carcinoma: An Overview of Toxicity and Dosing Strategies Oncologist, October 1, 2008; 13(10): 1084 - 1096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Dora, M. A. Leie, B. Netto, L. M. Fogliatto, L. Silla, F. Torres, and A. L. Maia Lack of imatinib-induced thyroid dysfunction in a cohort of non-thyroidectomized patients Eur. J. Endocrinol., May 1, 2008; 158(5): 771 - 772. [Full Text] [PDF]
|
|
|
|
|
|
S. A. Laurie, I. Gauthier, A. Arnold, F. A. Shepherd, P. M. Ellis, E. Chen, G. Goss, J. Powers, W. Walsh, D. Tu, et al. Phase I and Pharmacokinetic Study of Daily Oral AZD2171, an Inhibitor of Vascular Endothelial Growth Factor Tyrosine Kinases, in Combination With Carboplatin and Paclitaxel in Patients With Advanced Non-Small-Cell Lung Cancer: The National Cancer Institute of Canada Clinical Trials Group J. Clin. Oncol., April 10, 2008; 26(11): 1871 - 1878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Kelleher and R. McDermott Response to Sunitinib in Medullary Thyroid Cancer Ann Intern Med, April 1, 2008; 148(7): 567 - 567. [Full Text] [PDF]
|
|
|
|
|
|
L. Arnaud, N. E.C. Schartz, G. Bousquet, F. Sarandi, O. Verola, I. Madelaine, D. Kerob, and C. Lebbe Transient Sunitinib-Induced Coma in a Patient With Fibromyxoid Sarcoma J. Clin. Oncol., March 20, 2008; 26(9): 1569 - 1571. [Full Text] [PDF]
|
|
|
|
|
|
I. Tamaskar, R. Bukowski, P. Elson, A. G. Ioachimescu, L. Wood, R. Dreicer, T. Mekhail, J. Garcia, and B. I. Rini Thyroid function test abnormalities in patients with metastatic renal cell carcinoma treated with sorafenib Ann. Onc., February 1, 2008; 19(2): 265 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mannavola, P. Coco, G. Vannucchi, R. Bertuelli, M. Carletto, P. G. Casali, P. Beck-Peccoz, and L. Fugazzola A Novel Tyrosine-Kinase Selective Inhibitor, Sunitinib, Induces Transient Hypothyroidism by Blocking Iodine Uptake J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3531 - 3534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Stein and K. T. Flaherty CCR Drug Updates: Sorafenib and Sunitinib in Renal Cell Carcinoma Clin. Cancer Res., July 1, 2007; 13(13): 3765 - 3770. [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Feldman, A. J. Martorella, R. J. Robbins, and R. J. Motzer Re: Hypothyroidism in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib J Natl Cancer Inst, June 20, 2007; 99(12): 974 - 975. [Full Text] [PDF]
|
|
|
|
|
|
D. H. Garfield, A. Hercbergs, and P. J. Davis Re: Hypothyroidism in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib J Natl Cancer Inst, June 20, 2007; 99(12): 975 - 976. [Full Text] [PDF]
|
|
|
|
|
|
B. I. Rini Response: Re: Hypothyroidism in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib J Natl Cancer Inst, June 20, 2007; 99(12): 976 - 977. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Wolter, H. Dumez, P. Schoffski, and R. J. Motzer Sunitinib and Hypothyroidism N. Engl. J. Med., April 12, 2007; 356(15): 1580 - 1581. [Full Text] [PDF]
|
|
|
|
 |
|
 J. D Chouhan, D. E Zamarripa, P. H Lai, C. U Oramasionwu, and J. L Grabinski Sunitinib (Sutent(R)): A novel agent for the treatment of metastatic renal cell carcinoma Journal of Oncology Pharmacy Practice, March 1, 2007; 13(1): 5 - 15. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||