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Myositis - A common but underreported adverse effect of osimertinib: Case series and review of the literature.
Parafianowicz, P, Krishan, R, Beutler, BD, Islam, RX, Singh, T
Cancer treatment and research communications. 2020;:100254
Abstract
BACKGROUND Lung cancer is the second most common cancer in both men and women and the leading cause of cancer death worldwide. The development of novel tyrosine kinase inhibitors (TKIs) represented a paradigm shift in the management of lung cancer and has resulted in markedly prolonged survival. Osimertinib is a TKI that was fast-tracked by the United States Food and Drug Administration in 2015 and subsequently approved for the treatment of metastatic epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer. However, despite the generally favorable outcomes associated with osimertinib, rapid development and deployment of any new drug increases the risk of unforeseen adverse effects. Post-marketing surveillance studies therefore play an important role in further elucidating the risks and benefits of novel anti-neoplastic agents. MATERIAL AND METHODS We describe four patients with non-small cell lung cancer who developed myositis after beginning treatment with osimertinib. In addition, we review the literature on osimertinib-associated myositis. Using PubMed, the following terms were searched and relevant citations assessed: creatine phosphokinase, myositis, osimertinib, rhabdomyolysis, osimertinib, and Tagrisso. CASE PRESENTATION Thirty-eight patients were treated with osimertinib in our community clinic. Four with non-small cell lung cancer developed myositis after beginning treatment. The onset of symptoms and/or elevation of creatine phosphokinase occurred between two weeks and eleven months after osimertinib was initiated. Alternative causes for myositis were not identified. In two patients, myositis resolved within one month of withdrawing treatment. Two other patients continued osimertinib treatment with close monitoring. CONCLUSION Myositis is a serious and potentially underreported adverse effect of osimertinib. Previous studies suggest that osimertinib-associated myositis is rare, occurring in less than 1% of patients. However, myositis occurred in over 10% of patients treated with osimertinib in our clinic population. We suggest regular monitoring for myositis among patients being treated with osimertinib and dose-reduction or cessation of treatment if clinically indicated.
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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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Combined hepatocellular-cholangiocarcinoma successfully treated with sorafenib: case report and review of the literature.
Futsukaichi, Y, Tajiri, K, Kobayashi, S, Nagata, K, Yasumura, S, Takahara, T, Minemura, M, Yasuda, I
Clinical journal of gastroenterology. 2019;(2):128-134
Abstract
Sorafenib, a multiple kinase inhibitor, has been established as first-line standard systemic chemotherapy for patients with advanced hepatocellular carcinoma (HCC). We encountered a patient with combined hepatocellular and cholangiocarcinoma (CHC) who achieved complete remission in response to sorafenib treatment. A 58-year old man with hepatitis C virus (HCV)-induced liver cirrhosis was diagnosed with CHC in segments 6th and 7th of the liver and underwent partial surgical resection. Three months later, CHC recurred as metastases at multiple intrahepatic sites, lymph nodes, and bones, making surgery impossible. Treatment with sorafenib was initiated at 400 mg b.i.d., later reduced to 400 mg/day. After 6 months of sorafenib administration, he no longer showed abnormal uptake on fluorodeoxyglucose positron emission tomography. He was continued on sorafenib for 2.5 years, but later discontinued due to adverse events. He has shown no evidence of tumor recurrence more than 1 year after sorafenib discontinuation. His HCV was eradicated by direct-acting antivirals, and he remains in good health.
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Etoposide combined with ruxolitinib for refractory hemophagocytic lymphohistiocytosis during pregnancy: a case report and literature review.
Wang, S, Wu, J, Jing, X, Zhang, Y, Tang, H, Wu, J
Hematology (Amsterdam, Netherlands). 2019;(1):751-756
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is an immune-mediated disorder caused by uncontrolled inflammatory responses and the activation of T lymphocytes. This life-threatening disease, characterized by fever, cytopenia and hepatosplenomegaly, is extremely rare during pregnancy with high mortality. Despite the improvement of treatment regimen in recent years, HLH is still a great challenge for clinicians. Here, we described a 26-year-old woman who admitted to our hospital at her first pregnancy with pyrexia. Her condition continued to deteriorate after receiving broad-spectrum antimicrobials, presenting with fever, pancytopenia, hepatosplenomegaly, ferritin ≥ 500 μg/L, hemophagocytosis and low NK-cell activity. HLH was eventually diagnosed by clinical manifestation and laboratory examination results. Then the patient recovered well after treatment with etoposide combined with ruxolitinib therapy and underwent successful induced-labor operation. Additionally, we summarized similar cases from the literature to improve the management of HLH during pregnancy. In conclusion, this study highlights the challenges and difficulties in the diagnosis and management of patients with HLH during pregnancy. Moreover, this is the first case report of etoposide combined with ruxolitinib in the treatment of patients with refractory secondary HLH during pregnancy.