E-Newsletter - October 2015

Pivotal Alliance Trials Address Two Rare Population Subsets
Trial for Advanced Anaplastic Thyroid Cancer | Alliance A091305

While thyroid cancer is the most common endocrine malignancy, anaplastic thyroid cancer (ATC) is extremely rare. This year, the estimated incidence rate for thyroid cancer in the United States is about 62,450 newly diagnosed cases, of which ATC comprises less than 2 percent.1-3 ATC is an undifferentiated, highly aggressive tumor with a median survival of five months from diagnosis and a one-year survival of no more than 20 percent. Patients with ATC die from distant metastases or locoregional disease that obliterates the airway. Median age at diagnosis ranges between 63 and 74 years. ATC affects women more frequently than men.3 Symptoms at diagnosis include hoarseness (due to invasion of the trachea, larynx, or recurrent laryngeal nerve), dysphagia (due to invasion of the esophagus) and dyspnea.3 A diagnosis of ATC frequently follows a prior or concurrent diagnosis of well‑differentiated thyroid cancer or benign nodular thyroid disease, and synchronous pulmonary metastases may be present in up to 50 percent of patients.3 If detected early, extensive surgery offers the best chance of cure. Combination chemotherapy and hyperfractionated radiotherapy (RT) are used with limited success, but several clinical studies using taxanes have shown benefit.4-7 More effective targeted therapies based on a better understanding of the molecular and signaling pathways that are disrupted in ATC are needed.8-11

In Alliance A091305 (A phase 2 randomized study of efatutazone, an oral PPAR* agonist, in combination with paclitaxel versus paclitaxel in patients with advanced anaplastic thyroid cancer), Alliance researchers will determine how well efatutazone with paclitaxel compared to paclitaxel alone works in treating patients with advanced anaplastic thyroid cancer. Drugs used in chemotherapy, such as efatutazone and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells by stopping them from dividing or by stopping them from spreading. It is not yet known whether efatutazone in combination with paclitaxel is more effective than paclitaxel alone in treating patients with advanced anaplastic thyroid cancer.

This is a phase II randomized study for patients with advanced anaplastic thyroid cancer. Patients will be randomized to one of two treatment arms, efatutazone in combination with paclitaxel or paclitaxel alone. Treatment will consist of continuous cycles administered every 21 days. Treatment will continue until disease progression, unacceptable adverse events, or a minimum of two cycles beyond a complete response.

Some eligibility criteria for the study includes a diagnosis of advanced anaplastic thyroid cancer (ATC); disease is either metastatic (stage IVC) or locally advanced unresectable disease (stage IVB);  and no prior taxane therapy more than six months, except as a radiosensitizer. To learn more about this study, refer to the study protocol (Alliance A091305), which can be found on the CTSU menu (ctsu.org) and includes complete information on the trial design, treatment plan and patient eligibility. The Alliance Study Chair is Robert C. Smallridge, MD, Mayo Clinical Cancer Center, e-mail: smallridge.robert@mayo.edu. Also see ClinicalTrial.gov Identifier: NCT02152137.

* PPAR is an acronym for peroxisome proliferator-activated receptor, which are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. They play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms.

1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. (2015). SEER Stat Fact Sheets: Thyroid Cancer. Retrieved from http://seer.cancer.gov/statfacts/html/thyro.html
2. Abate E, Smallridge R 2011 Managing anaplastic thyroid cancer. Expert Rev Endocrinol Metab. 6:793-809.
3. Smallridge RC, Abate E 2014 In Press Anaplastic Thyroid Carcinoma: Clinical Aspects. In: Wartofsky L, Van Nostrand D, (eds) Thyroid Cancer: A Comprehensive Guide to Clinical Management. Third Edition ed. Springer.
4. Ain KB, Egorin MJ, DeSimone PA 2000 Treatment of anaplastic thyroid carcinoma with paclitaxel: phase 2 trial using ninety-six-hour infusion. Collaborative anaplastic thyroid cancer health intervention trials (CATCHIT) group. Thyroid. 10:587-594.
5. Bhatia A, Rao A, Ang KK, et al, Anaplastic thyroid cancer: clinical outcomes with conformal radiotherapy. Head Neck 2010;32:829-836..
6. Higashiyama T, Ito Y, Hirokawa M, et al. 2010 Induction chemotherapy with weekly paclitaxel administration for anaplastic thyroid carcinoma. Thyroid. 20:7-14.
7. Troch M, Koperek O, Scheuba C, et al. 2010 High efficacy of concomitant treatment of undifferentiated (anaplastic) thyroid cancer with radiation and docetaxel. J Clin Endocrinol Metab. 95:E54-57.
8. Smallridge RC, Copland JA 2010 Anaplastic thyroid carcinoma: pathogenesis and emerging therapies. Clin Oncol. 22:486-497.
9. Smallridge RC, Marlow LA, Copland JA 2009 Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocr Relat Cancer. 16:17-44.
10. Smallridge RC, Ain KB, Asa SL, et al. 2012 American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 22:1104-1139.
11. Smallridge RC 2012 Approach to the patient with anaplastic thyroid carcinoma. J Clin Endocrinol Metab. 97:2566-2572.


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For other articles in the October issue of Alliance E-News, see below.