Phase II study of lenalidomide in distantly metastatic, rapidly progressive, and radioiodine-unresponsive thyroid carcinomas: preliminary results

Ain, Kenneth B.; Lee, C.; Holbrook, K.; Dziba, Joshua M.; Williams, Kathleen

doi:10.1200/jco.2008.26.15_suppl.6027

Cited by 41 publications

(23 citation statements)

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“…Independent, blinded radiological review was rarely reported (19,20), despite recommendations as critical to minimize bias (78). Nonstandard response criteria have also been used in some trials (68,69).…”

Section: Discussionmentioning

confidence: 99%

“…Toxicities were dose limiting in the majority of patients, and the most common adverse events included somnolence, peripheral neuropathy, constipation, dizziness, and infection. Given the suggested efficacy but high rate of adverse events with thalidomide, a subsequent phase II study was initiated using the presumably less toxic lenalidomide (69). Eligibility was limited to DTC patients whose measured tumor volumes had increased by at least 30% in the past year.…”

Section: Thalidomidementioning

confidence: 99%

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Advances in Chemotherapy of Differentiated Epithelial and Medullary Thyroid Cancers

Sherman

2009

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context: Systemic chemotherapies for advanced or metastatic thyroid carcinomas have been of only limited effectiveness. For patients with differentiated or medullary carcinomas unresponsive to conventional treatments, novel therapies are needed to improve disease outcomes.Evidence Acquisition: The PubMed and Google Scholar search engines were used to identify publications and peer-reviewed meeting presentations addressing chemotherapy and targeted therapy for differentiated or medullary carcinoma.Evidence Synthesis: Multiple novel therapies primarily targeting angiogenesis have entered clinical trials for metastatic thyroid carcinoma. Partial response rates up to 30% have been reported in single agent studies, but prolonged disease stabilization is more commonly seen. The most successful agents target the vascular endothelial growth factor receptors, with potential targets including the mutant kinases associated with papillary and medullary oncogenesis. Two drugs approved for other malignancies, sorafenib and sunitinib, have had promising preliminary results reported, and are being used selectively for patients who do not qualify for clinical trials. Randomized trials for several agents are underway that may lead to eventual drug approval for thyroid cancer. thyroid carcinomas have limited effectiveness, with response rates typically 25% or less (1). With such poor outcomes, results from few clinical trials of new therapies for thyroid carcinomas were published during the latter half of the 20th century (2). Plaguing these early trials was the practice of lumping patients with all histologies of thyroid carcinoma (differentiated, medullary, and anaplastic), confounding interpretation of the results. The definitions of response used in these earlier studies varied as well, and none are comparable with the currently used standard RECIST methodology [for detailed description of RECIST, see Refs. 3, 4). Thus, treatment with cytotoxic chemotherapy is generally limited to patients with symptomatic or rapidly progressive metastatic disease unresponsive to or unsuitable for surgery, radioiodine (for tumors derived from differentiated carcinomas), and external beam radiotherapy. ConclusionDuring the past decade, biological discoveries sparked trials testing novel therapies for advanced thyroid carcinomas. Of prime importance has been recognition of key oncogenic mutations in papillary (PTC) and medullary (MTC) carcinomas. BRAF and RAS genes code for kinases that activate signaling through the MAPK pathway, regulating growth and function in many cells both normal and neoplastic. Evidence from various tumor models support the contention that most PTCs arise as a result of single activating somatic mutations in one of three genes: BRAF, RAS, and translocations producing RET/PTC oncogenes (5). The resultant RET/PTC proteins signal upstream from RAS, thus activating the same MAPK pathway. For MTC,

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Section: Discussionmentioning

confidence: 99%

Section: Thalidomidementioning

confidence: 99%

Advances in Chemotherapy of Differentiated Epithelial and Medullary Thyroid Cancers

Sherman

2009

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Chemotherapy with standard agents (e.g. doxorubicin, cisplatin and taxanes) and thalidomide has not been popular because of unconvincing results with significant toxicity, whereas a newer thalidomide analogue lenalidomide needs to be investigated further [23][24][25][26][27][28]. To summarize, the major issues with these agents have been the requirement for more consistent results from multiple centres that would further validate the initially reported promising results.…”

Section: Diagnostic Investigation Protocol and Interpretive Pitfallsmentioning

confidence: 99%

Defining a rational step-care algorithm for managing thyroid carcinoma patients with elevated thyroglobulin and negative on radioiodine scintigraphy (TENIS): considerations and challenges towards developing an appropriate roadmap

Basu

Dandekar

Joshi

et al. 2015

Eur J Nucl Med Mol Imaging

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One of the most challenging clinical situations in patients with differentiated thyroid cancer (DTC) is an elevated serum thyroglobulin (Tg) level with negative radioiodine scintigraphy (commonly termed BTENIS^). The diagnostic and therapeutic approaches adopted by attending physicians in day-to-day routine vary quite widely. The main reason for this variation is the rarity of the condition (2 -13 % from various series reported in literature), and its management, especially therapeutic strategies, continues to be imperfect in the absence of a clear-cut understanding and lack of evidence of its aetiology, as observed by various authorities [1]. In this editorial, we discuss the different therapeutic strategies that have been explored and the associated pitfalls in interpretation of clinical findings, and propose a logical step-wise algorithmic approach to care to follow in routine clinics in this particular group of patients. Our views are supported by an overview of the evidence in the literature (with respect to both efficacy and adverse effects) and by practical experience. In addition, we critically review and analyse the steps needed in the immediate future to enhance and rationalize patient care. We believe that such endeavours to identify and prioritize the challenges will further the roadmap to the development of a systematic and scientific approach to the management of patients with TENIS.

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“…The majority of patients required dose modifications because of toxicity. This same group of investigators is undertaking a phase II clinical trial of lenalidomide, with an interim analysis suggesting similar response rates to thalidomide but with lesser toxicity [89].…”

Section: Other Molecular Targeted Therapiesmentioning

confidence: 99%

“…Additionally, because of the nature of phase II clinical trials, there is no control group for comparison. Endpoints in most studies are either assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) [80] or by changes in tumor volume, with partial responses or stable disease being the most common outcomes [18,[81][82][83][84][85][86][87][88][89][90][91].…”

Section: Potential Molecular Targetsmentioning

confidence: 99%

Standard and Emerging Therapies for Metastatic Differentiated Thyroid Cancer

et al. 2010

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After completing this course, the reader will be able to:1. Describe the role and limitations of traditional treatments for metastatic differentiated thyroid cancer.2. Discuss the molecular basis of and clinical evidence for novel and emerging treatments for metastatic differentiated thyroid cancer.3. Identify suitable candidates for clinical trials among your patients with radioactive iodine refractory, metastatic differentiated thyroid cancer and enroll them.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACTDifferentiated thyroid cancer accounts for >90% of cases of thyroid cancer, with most patients having an excellent prognosis. Distant metastases occur in 10%-15% of patients, decreasing the overall 10-year survival rate in this group to 40%. Radioactive iodine has been the mainstay of treatment for distant metastases, with good results when lesions retain the ability to take up iodine. For patients with metastatic disease resistant to radioactive iodine, treatment options are few and survival is poor. Chemotherapy and external beam radiotherapy have been used in these patients, but with disappointing results. In recent years, our understanding of the molecular pathways involved in thyroid cancer has increased and a number of molecular targets have been identified. These targets include the protooncogenes BRAF and RET, known to be common mutations in thyroid cancer; vascular endothelial growth factor receptor and platelet-derived growth factor receptor, associated with angiogenesis; and the sodiumiodide symporter, with the aim of restoring its The Oncologist CME Program is located online at http://cme.theoncologist.com/.To take the CME activity related to this article, you must be a registered user. EndocrinologyThe

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Phase II study of lenalidomide in distantly metastatic, rapidly progressive, and radioiodine-unresponsive thyroid carcinomas: preliminary results

Cited by 41 publications

References 0 publications

Advances in Chemotherapy of Differentiated Epithelial and Medullary Thyroid Cancers

Advances in Chemotherapy of Differentiated Epithelial and Medullary Thyroid Cancers

Defining a rational step-care algorithm for managing thyroid carcinoma patients with elevated thyroglobulin and negative on radioiodine scintigraphy (TENIS): considerations and challenges towards developing an appropriate roadmap

Standard and Emerging Therapies for Metastatic Differentiated Thyroid Cancer

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