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1.
Lenvatinib complementary with radioiodine therapy for patients with advanced differentiated thyroid carcinoma: case reports and literature review.
Sheu, NW, Jiang, HJ, Wu, CW, Chiang, FY, Chiou, HC, Hsiao, PJ
World journal of surgical oncology. 2019;(1):84
Abstract
BACKGROUND The prognosis for patients with advanced differentiated thyroid carcinoma (ADTC) with disseminated distant metastases is very poor. Tyrosine kinase inhibitors targeting tumor angiogenesis have been shown to improve progression-free survival in patients with advanced thyroid carcinoma and progressive radioiodine-refractory thyroid carcinoma. Tyrosine kinase inhibitor has been reported as a successful neoadjuvant for total thyroidectomy to reduce tumor burden. However, the special indications for prompt treatment with lenvatinib as a rescue therapy to reduce tumor burden and prolong a durable response to radioiodine therapy have not been explored. CASE PRESENTATION Here, we present two ADTC cases with distant metastases who were effectively treated by total thyroidectomy combined with lenvatinib to prolong a durable response to radioiodine therapy. Case 1 was a 66-year-old male diagnosed with ADTC and disseminated brain, lung, and bone metastases. Lenvatinib was initiated via compassionate access because of rapidly progressive tumor growth even after second doses of radioiodine therapy and external beam radiation therapy for his brain metastases. The result was a durable response to lenvatinib, slowing progressive tumor growth for 3 years and allowing a third course of radioiodine therapy to treat the bone metastases. Case 2 was a 45-year-old male diagnosed with ADTC and diffuse disseminated lung metastases. Respiratory failure ensued after total thyroidectomy, requiring mandatory support by respirator. Lenvatinib was started as a rescue therapy to reduce tumor burden rapidly. The patient was successfully weaned off the respirator only 1 week after using lenvatinib. The patient was then maintained on a low dose of lenvatinib, allowing three subsequent courses of radioiodine therapy. Currently, his lung metastasis remains well controlled with decreased lung infiltrating nodules and the patient can tolerate exercise well. CONCLUSION Our case experience indicated that lenvatinib has significant value as salvage therapy, reducing tumor burden, producing a durable response and maintaining quality of life. For ADTC patients with progressive life-threatening metastases, our experience suggests that lenvatinib treatment can be used as an urgent rescue therapy as well as a complement to radioiodine therapy to improve tumor eradication.
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2.
Exceptional serological and radiological response to sorafenib in 2 patients with advanced hepatocellular carcinoma and chronic hepatitis C viral infection: case report and review of the literature.
Atkin, C, Earwaker, P, Pallan, A, Shetty, S, Punia, P, Ma, YT
BMC gastroenterology. 2017;(1):30
Abstract
BACKGROUND In patients with advanced hepatocellular carcinoma (HCC), the multikinase inhibitor sorafenib is the only systemic treatment that has been shown to increase overall survival. However, similar to other tyrosine kinase inhibitors, most patients achieve disease stabilisation radiologically, and only 2-3% of patients achieve a partial response. Recent exploratory subgroup analyses of the large phase 3 trials have demonstrated that patients with chronic hepatitis C virus (HCV) infection associated HCC survive longer than those who are negative for HCV. The mechanism underlying this currently remains unknown. A small number of cases of complete response to sorafenib treatment have now been reported worldwide, however a prolonged response has only been reported in 2 cases, both of whom had HCV-related HCC. CASE PRESENTATION A 55 year old gentleman was diagnosed with hepatocellular carcinoma and concomitant chronic hepatitis C viral infection. He progressed following transarterial chemoemoblisation treatment and was commenced on sorafenib treatment. His serum alphafetoprotein level normalised within 2 months of treatment and he achieved an almost complete radiological response. This response was maintained for 20 months before the patient progressed. A 75 year old lady was diagnosed with advanced hepatocellular carcinoma and concomitant chronic hepatitis C viral infection. She was commenced on sorafenib treatment but required early dose reductions due to palmar plantar erythrodysesthesia, and liver decompensation. Despite this she achieved an excellent serological and radiological response that was maintained for 24 months. CONCLUSIONS Our two cases show that patients with HCV-associated HCC can attain excellent responses to sorafenib treatment that is durable. Furthermore, such exceptional responses can be achieved even with dose reductions and treatment breaks.
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3.
Complete and Sustained Off-Therapy Response to Sorafenib in Advanced Hepatocellular Carcinoma.
Maida, M, Macaluso, FS, Valenza, F, Virdone, R
Journal of gastrointestinal and liver diseases : JGLD. 2016;(2):253-5
Abstract
UNLABELLED A 75-year-old Caucasian woman with alcohol-related cirrhosis was admitted to our Unit in October 2012 for the diagnostic evaluation of a focal liver lesion detected by regular surveillance ultrasound. The subsequent dynamic CT and MR led to a diagnosis of infiltrative hepatocellular carcinoma (HCC) of 5 cm in the hepatic segment IV with neoplastic infiltration of the left branch of the portal vein, in absence of extrahepatic metastases. Therapy with sorafenib 400 mg bid was started and the subsequent dynamic CT performed at the 10th month of therapy showed a complete response according to RECIST criteria and mRECIST, while seriated dosages of α-fetoprotein levels showed a progressive reduction up to normalization. After 18 months of therapy, Sorafenib was discontinued due to a grade 3 adverse event. Nonetheless, all subsequent radiological controls, performed over the following two years confirmed a complete off-therapy response despite withdrawal of Sorafenib. After three years the patient is asymptomatic, with a preserved liver function and undetectable solid tumor lesions at dynamic CT. This case represents one of the few examples of complete response to anti-angiogenic drugs and, to our knowledge, the only case of sustained response, even after the discontinuation of Sorafenib, described so far in the literature. KEY WORDS hepatocellular carcinoma - HCC - BCLC - sorafenib - complete response. ABBREVIATIONS AFP: alpha-fetoprotein; AE: adverse event; BCLC Barcelona Clinic Liver Cancer; CT: computed tomography; HCC: hepatocellular carcinoma; mRECIST modified response evaluation criteria in solid tumors; PS: Performance status; RCTs: randomized controlled trials.
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4.
Multitargeted Kinase Inhibition in Metastatic Differentiated Radioiodine-Refractory Thyroid Cancer: A Look at New Therapeutic Options for a Rare Disease.
Mischler, K, Kneifel, S, Cathomas, R
Oncology research and treatment. 2016;(9):548-52
Abstract
BACKGROUND Metastatic differentiated thyroid cancer (DTC) is a rare disease that is in the first line treated with iodine-131 radioisotope therapy. Until recently, options were very limited in the case of progressive radioactive-iodine (RAI)-refractory disease. Based on new study results, tyrosine kinase inhibitors (TKIs) have attracted attention. The TKI sorafenib demonstrated significantly improved progression-free survival (PFS) in a phase III trial. Recent data from another phase III trial showed that the TKI lenvatinib achieved high response rates and a large improvement in PFS in metastatic RAI-refractory DTC patients in the first-line setting and after 1 prior line of TKI. However, little is known about the response to lenvatinib in patients pretreated with multiple lines of TKIs. CASE REPORT We present the case of a 45-year-old man with metastatic RAI-refractory DTC progressing after multiple prior treatments with TKIs and chemotherapy. A very good and long-lasting response to lenvatinib was observed. Careful and prospective monitoring as well as management of side effects including dose adaptation were necessary to ensure success of treatment. CONCLUSION Here, we review different novel treatment options for patients with metastatic RAI-refractory DTC.
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5.
Case analysis of complete remission of advanced hepatocellular carcinoma achieved with sorafenib.
Liu, D, Liu, A, Peng, J, Hu, Y, Feng, X
European journal of medical research. 2015;(1):12
Abstract
BACKGROUND To evaluate the feasibility and security of complete remission (CR) of advanced hepatocellular carcinoma (HCC) achieved with sorafenib treatment, and investigate the previously described predictive factors in CR. METHODS The case of a patient who achieved CR of advanced HCC with sorafenib treatment was analyzed. The case analysis was performed by a literature review of relevant reports retrieved from the PubMed database. RESULTS A 58-year-old male patient achieved CR of advanced HCC after 23 weeks of oral treatment with sorafenib alone for 41 months and maintained CR for more than 35 months. Eleven reports worldwide have documented a total of twelve patients who achieved CR of advanced HCC, including six with nonsurgical oral sorafenib treatment, four with surgical resection in the descent stage following oral sorafenib treatment and two with oral sorafenib treatment for postoperative metastasis. CONCLUSIONS For unresectable advanced HCC, sorafenib can significantly improve progression-free survival and overall survival, achieving CR in some cases. In addition, surgical resection of advanced HCC in the descent stage is possible following oral sorafenib treatment. For patients with postoperative distant metastasis of HCC, sorafenib treatment also provides clinical benefits and can even achieve CR. Besides, long-term sorafenib administration is safe, and patients should continually receive sorafenib to avoid recurrence after complete remission of cancer. Furthermore, early HFSR, rapid decline of AFP levels and rapid tumor shrinking observed by imaging are known parameters describing sorafenib's effects. Finally, it is important to assess the gene locus of sorafenib sensitivity in HCC patients in future research.
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6.
Severe human poisoning with a flufenoxuron-containing insecticide: Report of a case with transient myocardial dysfunction and review of the literature.
Woo, JH, Lim, YS
Clinical toxicology (Philadelphia, Pa.). 2015;(6):569-72
Abstract
CONTEXT Flufenoxuron (Cascade™) is a new benzoylurea insecticide. We describe a case of human poisoning with previously unreported cardiac complications and review other case reports in the literature. CASE DETAILS A 54-year-old stuporous man who had ingested a flufenoxuron-containing insecticide presented to the emergency department with severely unstable vital signs and lactic acidosis which continued to worsen over time. He was treated with gastric lavage and infusion of sodium bicarbonate, crystalloid, and dopamine. The patient was initially unresponsive, but recovered from shock after norepinephrine treatment. While electrocardiography showed no abnormal findings, cardiac enzymes remained elevated for several days. Initial echocardiography showed global left ventricular hypokinesia and a left ventricular ejection fraction of 40%, but echocardiography after 45 h showed normal results. On the sixth day, he was discharged after rejecting medical advice for further evaluation. DISCUSSION Severe lactic acidosis, shock, elevation of cardiac enzymes, and global left ventricular hypokinesia can occur in human poisoning with flufenoxuron-containing insecticide, and norepinephrine is preferable for the management of shock.
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7.
Long-term complete response of advanced hepatocellular carcinoma treated with multidisciplinary therapy including reduced dose of sorafenib: case report and review of the literature.
Shinoda, M, Kishida, N, Itano, O, Ei, S, Ueno, A, Kitago, M, Abe, Y, Hibi, T, Yagi, H, Masugi, Y, et al
World journal of surgical oncology. 2015;:144
Abstract
An 83-year-old man underwent computed tomography during a routine check-up due to a history of surgical treatment for pancreatic cancer. Two tumors were detected in the anterior segment of the liver. A needle biopsy of the larger tumor was performed, and pathological examination showed that the tumor was a poorly differentiated hepatocellular carcinoma. Resection was not performed considering the patient's poor physical condition. Thus, transcatheter arterial chemoembolization and radiofrequency ablation of the tumors were performed. Three months later, residual tumor of the larger lesion and multiple pulmonary metastases were detected. This time, continuous hepatic arterial infusion chemotherapy was performed. Although the pulmonary metastases markedly reduced, tumor thrombi appeared in the right portal vein on computed tomography. Finally, sorafenib was administered, which led to disappearance of the tumor thrombi and no other signs of recurrence 8 months after initiation of sorafenib on computed tomography. Although sorafenib administration has continued at reduced doses of 200 mg per day or less due to hypertension, complete response has persisted for the past 34 months. It is noteworthy that sorafenib has been given at reduced doses, but a long-term complete response is maintained in a patient who had portal tumor thrombi and distant metastasis. Herein, we present this rare case of advanced hepatocellular carcinoma controlled with reduced doses of sorafenib following multidisciplinary therapy, describe our single center experience with sorafenib use in patients with hepatocellular carcinoma, and review previous reports that focused on dose reduction of sorafenib.
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8.
Sorafenib as monotherapy or in association with cytarabine and clofarabine for the treatment of relapsed/refractory FLT3 ITD-positive advanced acute myeloid leukemia.
Fontanelli, G, Rocco, M, Caracciolo, F, Benedetti, E, Buda, G, Orciuolo, E, Carulli, G, Galimberti, S, Azzarà, A, Petrini, M
Clinical lymphoma, myeloma & leukemia. 2014;(1):e13-7
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9.
Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib.
Choi, JI, Imagawa, DK, Bhosale, P, Bhargava, P, Tirkes, T, Seery, TE, Lall, C
Clinical and molecular hepatology. 2014;(2):218-22
Abstract
Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
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10.
Recurrent ascites in a patient with low-grade astrocytoma and ventriculo-peritoneal shunt treated with the multikinase inhibitor sorafenib.
Legault, G, Kieran, MW, Scott, RM, Chordas, C, Milla, SS, Karajannis, MA
Journal of pediatric hematology/oncology. 2014;(8):e533-5
Abstract
This report describes a 6-year-old boy with disseminated low-grade astrocytoma and ventriculo-peritoneal shunt, who developed recurrent ascites while receiving sorafenib on a clinical trial. Laboratory analysis of the peritoneal fluid showed no elevation of protein content and no evidence of underlying infection or tumor dissemination. This report highlights ascites as a previously unrecognized adverse reaction to sorafenib in a patient with a ventriculo-peritoneal shunt. We conclude that such patients should be closely monitored for this complication when treated with sorafenib.