Researchers at Penn Medicine recently completed a phase II trial of sorafenib (Nexavar®), a promising new agent for the treatment of metastatic, iodine-refractory thyroid carcinoma.
Led by Marcia S.Brose,MD,PhD, the research team included members of both the Abramson Cancer Center of the University of Pennsylvania and the Center for Head and Neck Cancer at Penn.
The trial population included a spectrum of thyroid cancer histologic subtypes, including differentiated, anaplastic, medullary and nonmedullary cancers. All patients had progressive disease at baseline.
Sorafenib, an oral multi-kinase inhibitor currently approved for the treatment of non-resectable hepatocellular carcinoma and advanced renal cell carcinoma, was administered at a dose of 400mg orally twice daily for a minimum of 16 weeks.
Dose adjustments were made as needed for toxicity. Study endpoints included best objective response rate and progression-free survival.
On the basis of findings from the first 30 trial participants, the Penn team concluded that sorafenib represents a significant advance over chemotherapy in both response rate and progression-free survival (PFS) for patients with metastatic, iodine-refractory thyroid carcinoma.
The overall clinical benefit rate for these patients (defined as partial response plus stable disease) was 77%. Median progression-free survival (PFS) was 79 weeks.
No patient died before disease progression and no significant differences in PFS were observed between follicular and papillary subtypes. Treatment related adverse events were predominantly of grade 1 or 2, with the most common events including palmar-plantar erythema, rash, fatigue, stomatitis/mucositis, weight loss, and musculoskeletal pain.
The trial report was published in the Journal of Clinical Oncology in October 2008.1
Mr. K, a 37-year-old man, was referred to Penn Medicine by his internist after discovering a lump in his neck. His medical history was previously unremarkable.
At Penn, a needle aspiration biopsy determined that the lump was a follicular carcinoma. Mr. K was scheduled for a thyroidectomy and bilateral central neck lymph node dissection. Of the 32 lymph nodes removed from Mr. K’s central and right lateral neck, 14 were positive for cancer.
A subsequent total body PET scan revealed lesions in his left lung and kidney. Mr. K was diagnosed with metastatic iodine-nonavid differentiated thyroid cancer. With an anticipated survival of approximately eight months, Mr. K agreed to participate in the Phase II clinical trial of sorafenib in thyroid cancer at Penn.
Within two months of initiating therapy at 400 mg bid, the progression of Mr. K’s disease stabilized; a marked decrease in both thyroglobulin levels and CT-documented tumor burden was noted.
At six months, Mr. K experienced palmar erythema, which responded well to anti-inflammatory agents; he had no other significant adverse effects during treatment. At 27 months post-treatment, his disease remained progression-free and he was otherwise healthy.
1. Gupta-Abramson V, Traxel AB, Nellore A, Puttaswamy K, Redlinger M, Ransone K, Mandel SJ, Flaherty KT, Loevner LA, O’Dwyer PJ, Brose MS. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol. 2008;26:4714-4719.
The treatment of cancer at Penn Medicine involves more than 300 specialists and researchers collaborating under the auspices of the Abramson Cancer Center of the University of Pennsylvania, a national leader in cancer research, patient care, training, community education, and outreach.
At Penn, cancer patients are managed by oncologists, surgeons and radiation oncologists who specialize in the diagnosis and treatment of specific cancers; aftercare is tailored to address the emotional challenges facing cancer patients and their families––and all of these elements take place in a setting devoted to basic, translational, clinical and cancer control research.
Department of Otorhinolaryngology – Head and Neck Surgery
Marcia S. Brose, MD, PhD
Assistant Professor of Otorhinolaryngology
Director, Cancer Genetics Laboratory Abramson Cancer Center
Division of Endocrinology
Susan J. Mandel, MD, MPH
Professor of Medicine
Head and Neck Oncology
Abramson Cancer Center
Perelman Center for Advanced Medicine, West Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104
Thyroid Cancer Clinical Research at the Abramson Cancer Center
Clinical research is a fundamental mission of the Abramson Cancer Center of the University of Pennsylvania. To determine whether a patient is eligible for a following trial, please visit oncolink.org and click on “Cancer Clinical Trials Matching” in the left-hand column.
Title: An International, Randomized, Double-Blinded, Phase 3 Efficacy Study of XL184 Versus Placebo in Subjects With Unresectable, Locally Advanced, or Metastatic Medullary Thyroid Cancer Phase: III Rationale: The purpose of this research study is to evaluate the progression-free survival (PFS) with XL184 as compared with placebo (an inactive substance) in subjects with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). Subjects will be randomized to receive XL184 or placebo in a 2:1 ratio. XL184 is an investigational drug that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.
Title: A Phase 1/2 Dose Finding Study of an Experimental New Drug CS7017, an Oral PPARã Agonist Taken by Mouth Twice Daily in Combination With Paclitaxel Chemotherapy Administered Every Three Weeks by Venous Infusion by Patients With Anaplastic Thyroid Cancer Phase: I/II Rationale: The Phase I/II study will be conducted as an open label, multiple center study of CS-7017, an experimental drug and paclitaxel chemotherapy in subjects with advanced anaplastic thyroid cancer. Biopsies will be obtained from patients with accessible tumor at baseline, two-weeks after the first CS-7017 dosage (prior to the start of combination therapy) and at the end of the first study cycle (week 3 of combination therapy), in order to evaluate the effects of the study drug alone and in combination with the chemotherapy agent on the tumor. Treatment will continue until disease progression or the development of intolerable toxicities.
To refer a patient and/or consult with a physician, Call 800-789-PENN (7366) or visit: PennMedicine.org/referral
Downloadf a pdf of this Clinical Briefing.