Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 3092
© 2006 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schoeffski, P. Articles by Dumez, H. Search for Related Content PubMed Articles by Schoeffski, P. Articles by Dumez, H.

Abstract

Sunitinib-related thyroid dysfunction: A single-center retrospective and prospective evaluation

University Hospital, Leuven, Belgium; Pfizer Inc., La Jolla, CA

3092

Background: Sunitinib is a multi-target tyrosine kinase inhibitor with anti-angiogenic and anti-proliferative activity mediated by signal blockade of VEGFR1/2, KIT, PDGFR/ß, and FLT-3. Phase II/III trials have demonstrated efficacy of the oral agent in Imatinib-resistant GIST and advanced renal cell cancer (RCC). We observed several cases of thyroid dysfunction in GIST during treatment with sunitinib suggesting that the drug may be associated with hypothyroidism. We therefore assessed the incidence and severity of thyroid dysfunction in cancer patients treated with sunitinib. Methods: Thyroid function (serum TSH, T3 and free thyroxin index) and thyroid antibodies (anti-TPO, -Tg and TSH-R-Ab) were evaluated retrospectively in a cohort of patients with GIST in a Phase III trial and in an expanded access program (1st part of the investigation) and in a prospective cohort of RCC and GIST patients treated in the framework of expanded access programs (2nd part). Sunitinib was given at a daily oral dose of 50 mg 4 weeks on, 2 weeks off. Thyroid parameters were assessed on days 1 and 28 of each treatment cycle in the prospective cohort. We report here the first TSH results, the full data set will be available at ASCO. Results: We identified a total of 46 patients who received sunitinib, and 33 of these patients were evaluable for thyroid function. 14 patients were analyzed retrospectively (all GIST), 19 patients prospectively (8 GIST, 11 RCC). 7 of these 19 patients (37%) showed an elevated TSH (>5 mIU/L) during treatment. In the retrospective analysis of 14 patients with a median treatment duration of 44 weeks, 8 patients (57%) had developed hypothyroidism. All patients with GIST in randomized Phase III trial remaining under active treatment with sunitinib for 58–80 weeks show an increased TSH (up to 83 mIU/L) during the course of treatment, requiring hormone substitution. In a cohort of 11 patients with RCC, after 6 weeks of treatment, 3 patients already have an increased TSH. Conclusions: Sunitinib is associated with a high incidence of thyroid dysfunction which requires further study. The mechanism by which Sunitinib induces thyroid dysfunction is yet unclear.

No significant financial relationships to disclose.

Abstract presentation from the 2006 ASCO Annual Meeting