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      Rapid pleural effusion after discontinuation of lenvatinib in a patient with pleural metastasis from thyroid cancer

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          Summary

          We report a case of rapid pleural effusion after discontinuation of lenvatinib. A 73-year-old woman was diagnosed with poorly differentiated thyroid cancer with right pleural metastasis. Weekly paclitaxel treatment was performed for 18 weeks, but it was not effective. Oral administration of lenvatinib, a multi-target tyrosine kinase inhibitor, reduced the size of cervical and thoracic tumors and lowered serum thyroglobulin levels. Lenvatinib was discontinued on day 28 because of Grade 2 thrombocytopenia and Grade 3 petechiae. Seven days after discontinuation of lenvatinib, the patient was hospitalized because of dyspnea and right pleural effusion. Pleural effusion rapidly improved with drainage and re-initiation of lenvatinib and did not recur. Anorexia caused by lenvatinib led to undernutrition, which resulted in death 13 months after initiation of lenvatinib. Autopsy revealed extensive necrosis with primary and metastatic lesions, suggesting that the patient responded to lenvatinib. Physicians should be aware of the possibility of flare-up in patients with thyroid cancer treated with lenvatinib.

          Learning points:
          • Autopsy findings revealed that lenvatinib was efficacious in treating poorly differentiated thyroid cancer without primary lesion resection.

          • Flare-up phenomenon may occur in thyroid cancer treated with lenvatinib.

          • Attention should be paid to flare-up phenomenon within a few days of discontinuing lenvatinib.

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          Most cited references8

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          Disease flare after tyrosine kinase inhibitor discontinuation in patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib: implications for clinical trial design.

          Treatment of patients with oncogene-addicted cancers with tyrosine kinase inhibitors (TKI) is biologically and clinically different than with cytotoxic chemotherapy. We have observed that some patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib (RECIST progression after initial benefit) have accelerated progression of disease after discontinuation of TKI. To examine this observation and define the course of patients following TKI discontinuation, we systematically evaluated patients enrolled on clinical trials of agents to treat acquired resistance to erlotinib or gefitinib. We evaluated patients with EGFR-mutant lung cancer who participated in trials for patients with acquired resistance that mandated TKI discontinuation before administration of study therapy. Disease flare was defined as hospitalization or death attributable to disease progression during the washout period. Fourteen of 61 patients (23%; 95% CI: 14-35) experienced a disease flare. The median time to disease flare after TKI discontinuation was 8 days (range 3-21). Factors associated with disease flare included shorter time to progression on initial TKI (P = 0.002) and the presence of pleural (P = 0.03) or CNS disease (P = 0.01). There was no association between disease flare and the presence of T790M at the time of acquired resistance. In patients with EGFR-mutant lung cancer and acquired resistance to epidermal growth factor receptor TKIs, discontinuation of erlotinib or gefitinib before initiation of study treatment is associated with a clinically significant risk of accelerated disease progression. Clinical trials in this patient population must minimize protocol-mandated washout periods. ©2011 AACR
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            Lenvatinib for Anaplastic Thyroid Cancer

            Background Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need. Patients and methods This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015. Patients received lenvatinib 24 mg daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and the secondary endpoint was efficacy, as assessed by progression-free survival (PFS), overall survival (OS), and objective response rate. Results At data cutoff, 17 patients with ATC were enrolled. All experienced ≥1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were decreased appetite (82%), hypertension (82%), fatigue (59%), nausea (59%), and proteinuria (59%). Of note, only one patient required lenvatinib withdrawal because of a TEAE, and this TEAE was considered unrelated to lenvatinib. The median PFS was 7.4 months [95% confidence interval (CI): 1.7–12.9], the median OS was 10.6 months (95% CI: 3.8–19.8), and the objective response rate was 24%. Conclusion In this study, lenvatinib demonstrated manageable toxicities with dose adjustments and clinical activity in patients with ATC. This clinical activity of lenvatinib warrants further investigation in ATC. ClinicalTrials.gov NCT01728623.
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              Poorly differentiated and anaplastic thyroid cancer.

              Poorly differentiated thyroid carcinoma (PDTC) and anaplastic (undifferentiated) thyroid carcinoma (ATC) comprise a small subset of thyroid tumors that are associated with a poor prognosis and account for a significant portion of the morbidity and mortality related to thyroid cancer. Since management strategies vary between these two entities, it is important for clinicians to be able to differentiate PDTC from ATC. We reviewed the literature on PDTC and ATC and compared clinical and histopathologic features important in defining the disease process. Both PDTC and ATC display aggressive behavior with increased locoregional and distant disease. In most cases, patients are older and have large, locally advanced tumors. PDTC may represent an intermediate entity in the progression of well-differentiated thyroid carcinoma to ATC. The use of surgical management may be curative or palliative and differs between PDTC and ATC. The roles of radiotherapy and chemotherapy have not been well described. PDTC and ATC are rare diseases that carry a poor prognosis. Recognition of their different clinicopathologic features is important to the optimal management of these tumors.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                18 March 2019
                2019
                : 2019
                : 18-0158
                Affiliations
                [1 ]Department of Neurology , Respirology, Endocrinology and Metabolism, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
                [2 ]Department of Diagnostic Pathology , University of Miyazaki Hospital, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
                [3 ]Department of Clinical Oncology , Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
                [4 ]Division of the Gastrointestinal , Endocrine and Pediatric Surgery, Department of Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
                Author notes
                Correspondence should be addressed to M Nakazato; Email: nakazato@ 123456med.miyazaki-u.ac.jp
                Article
                EDM180158
                10.1530/EDM-18-0158
                6432980
                30884464
                234ba50a-ffd4-43b7-9b54-45c2318b3d5e
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 04 February 2019
                : 26 February 2019
                Categories
                Unusual Effects of Medical Treatment

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