New Therapies for Thyroid Cancer [Новость добавлена - 03.12.2008]

Sorafenib and axitinib demonstrated activity against recurrent and metastatic disease.

Only a minority of thyroid cancer patients develop locally recurrent or
metastatic disease that is not curable with local therapy or I-131
treatment. However, treatment options for this small cohort have been
limited; the only FDA-approved chemotherapy agent for thyroid cancer is
adriamycin, which has shown only modest efficacy. Fortunately, our
understanding of thyroid cancer's underlying biology has grown dramatically
during the past decade, and this advancement has opened the way to
investigation of targeted agents and identification of new therapies.
Researchers now report results of two phase II studies of potentially
active oral agents.

In one trial, investigators evaluated the efficacy of sorafenib (Nexavar),
a multikinase inhibitor that blocks vascular endothelial growth factor
(VEGF) and B-Raf signaling pathways, both of which are implicated in
thyroid cancer. The researchers assessed outcomes in 30 patients with
advanced thyroid cancer deemed incurable (18 papillary, 9
follicular/Hurthle cell, 2 anaplastic/poorly differentiated, 1 medullary)
who received sorafenib (400 mg twice daily). Tumor measurements were
repeated at 8 weeks, at 16 weeks, and at 12-week intervals thereafter.
Median progression-free survival (PFS) was 79 weeks. Seven patients (23%)
achieved partial responses (PRs), and 16 patients (53%) had stable disease.
Patients with anaplastic/poorly differentiated carcinomas had no responses;
the patient with medullary thyroid cancer had stable disease. Toxicity was
substantial: 6 patients (20%) discontinued therapy because of toxicity, 14
(47%) required dose reductions, and 10 (33%) required adjustments of their
thyroid hormone therapy as a result of thyroid-stimulating hormone (TSH)
levels that rose above 0.10 mU/L.

In a second trial, investigators evaluated axitinib (an oral VEGF
inhibitor) in 60 patients with advanced thyroid cancer (30 papillary, 15
follicular [11 Hurthle cell variant], 11 medullary, 2 anaplastic, 2 other).
Patients had incurable disease with no evidence of hemoptysis, central
pulmonary lesions, or hypertension. Patients received axitinib (5 mg twice
daily; dose increased to 7 mg twice daily in the absence of grade 2
toxicity or blood pressure elevation >150/90 mm Hg). Tumors were measured
every 8 weeks. Median PFS was 18.1 months. Eighteen patients (30%)
experienced PRs, and 23 (43%) had stable disease. Responses were noted for
all pathologic subtypes. Eight patients (13%) discontinued therapy because
of toxicity. Fifteen patients were not eligible for response: 8 did not
meet response criteria, and 7 had no post-baseline data.

Comment: The role of medical oncologists in the treatment of thyroid cancer
has been limited because of the paucity of effective systemic agents. This
situation is destined to improve now that a number of targeted agents have
demonstrated moderate activity in recurrent and metastatic disease.
Responses to axitinib in patients with Hurthle cell, medullary, and
anaplastic/poorly differentiated thyroid tumor subtypes are especially
noteworthy because these tumors have been refractory to systemic
chemotherapy.

-- Barbara A. Murphy, MD

Published in Journal Watch Oncology and Hematology December 2, 2008
Citation(s):

Gupta-Abramson V et al. Phase II trial of sorafenib in advanced thyroid
cancer. J Clin Oncol 2008 Oct 10; 26:4714. (Subscription may be required)
(Free)

Cohen EEW et al. Axitinib is an active treatment for all histologic
subtypes of advanced thyroid cancer: Results from a phase II study. J Clin
Oncol 2008 Oct 10; 26:4708. (Subscription may be required) (Free)<!--
ARTICLE_TEXT = $ARTICLE_TEXT -->

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