Management of tyrosine kinase inhibitors (TKI) side effects in differentiated and medullary thyroid cancer patients

Resteghini, Carlo; Cavalieri, Stefano; Galbiati, Donata; Granata, Roberta; Alfieri, Salvatore; Bergamini, Cristiana; Bossi, Paolo; Licitra, Lisa; Locati, Laura D.

doi:10.1016/j.beem.2017.04.012

Cited by 69 publications

(65 citation statements)

References 48 publications

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“…Outcomes may be further improved by AE management. The prevention of toxicities is necessary to allow patients to remain on treatment as long as possible without dose or schedule modifications (27).…”

Section: Discussionmentioning

confidence: 99%

Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors

et al. 2019

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In patients with distant metastasis, treatment for differentiated thyroid cancer (DTC) includes complete total thyroidectomy, followed by radioactive iodine (RAI) therapy for metastatic lesions. Tyrosine kinase inhibitor (TKI) treatment is the final treatment option for metastatic lesions, which is incurable with surgery/RAI therapy. The present study examined whether treatment outcomes for DTC in patients with distant metastasis improved following TKI treatment. This study included 147 patients (median age, 71; range, 33-91 years) who underwent surgery in our hospitals and were diagnosed with distant metastasis. Disease progression was observed in 70 patients, of whom 56 were treated with TKI (TKI group); 14 refused TKI treatment or showed no treatment indication [untreated (UT) group]. Disease progression and treatment outcomes were assessed using imaging evaluations. The present study investigated thyroglobulin doubling time (Tg-DT) and Tg antibody presence/absence and their relation to disease progression. Overall survival following disease progression between the two groups was compared. The study included 22 cases of sorafenib, 49 of lenvatinib, and 15 involving TKIs. The mean dosing period for sorafenib was 153 days and for lenvatinib was 462 days. In the TKI group, 16, 26, and 9 patients exhibited partial responses (PRs), stable disease (SD), and progressive disease (PD), respectively, whereas 5 patients were not evaluable. The disease control rate (DCR) (PR+SD) was 75.0%. A total of 16 patients died in the TKI group, whereas 10/14 patients in the UT group died. Survival curves for the groups were significantly different. TKI treatment improved the prognosis of patients with distant metastasis and PD.

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Section: Discussionmentioning

confidence: 99%

Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors

et al. 2019

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“…In such cases, a second MKI might be considered. Of note, the discontinuation of an MKI treatment could lead to a rapid increase in tumor growth and disease progression (Resteghini et al 2017, Trimboli et al 2018.…”

Section: Molecular Target Therapy: Multikinase Inhibitorsmentioning

confidence: 99%

Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives

Ceolin

Duval

Benini

et al. 2019

Endocrine-Related Cancer

101

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Medullary thyroid carcinoma (MTC) is a rare type of tumor that originates from thyroid C cells and accounts for 2–4% of all malignant thyroid neoplasms. MTC may occur sporadically or be inherited, as part of the MEN 2 syndrome. Germline mutations of the RET (REarranged during Transfection) proto-oncogene cause hereditary cancer, whereas somatic RET mutations and, less frequently, RAS mutations have been described in sporadic MTC samples. Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC. Nevertheless, despite recent advances, the management of advanced, progressive MTC remains challenging. The multikinase inhibitors (MKI), vandetanib and cabozantinib, were approved for the treatment of progressive or symptomatic MTC, and several other compounds have exhibited variable efficacy. Although these drugs have been shown to improve progression-free survival, no MKI has been shown to increase the overall survival. As these drugs are nonselective, significant off-target toxicities may occur, limiting achievement of the required TK-specific inhibition. Recently, next-generation small-molecule TKI has been developed. These TKI are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. Here, we summarize the current understanding of the intracellular signaling pathways involved in MTC pathogenesis as well as the therapeutic approaches and challenges for the management of advanced MTC, focusing on targeted molecular therapies.

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“…Education of the patient before the start of therapy plays an important role because the probability and severity of the most frequent toxicities of TKIs may be lowered by preventive measures, that is, manicure, pedicure, or proper treatment of preexisting arterial hypertension. Also, general supportive means are to be considered to maintain the patient's quality of life (37).…”

Section: Practical Aspects Of Tki Treatment In Advanced Tcmentioning

confidence: 99%

“…Side effects, which often occur during the course of TKI treatment, have to be addressed appropriately to maintain quality of life because the drugs need to be administered continuously to keep the tumor under control (37). Many toxicities such as diarrhea, hypertension, fatigue, weight loss, and hand-foot skin reaction are also observed with other antitumor drugs and in other cancers, and their management is alike.…”

Section: During Tki Treatmentmentioning

confidence: 99%

“…Many toxicities such as diarrhea, hypertension, fatigue, weight loss, and hand-foot skin reaction are also observed with other antitumor drugs and in other cancers, and their management is alike. Especially for sorafenib, which has long been approved for the treatment of other malignancies, there is considerable knowledge of how to treat side effects once they occur (37)(38)(39). On the management of lenvatinib therapy, recently a comprehensive review article was published (40).…”

Section: During Tki Treatmentmentioning

confidence: 99%

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Current Treatment Strategies in Metastasized Differentiated Thyroid Cancer

2018

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Management of tyrosine kinase inhibitors (TKI) side effects in differentiated and medullary thyroid cancer patients

Cited by 69 publications

References 48 publications

Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors

Treatment outcomes of differentiated thyroid cancer with distant metastasis improve by tyrosine kinase inhibitors

Medullary thyroid carcinoma beyond surgery: advances, challenges, and perspectives

Current Treatment Strategies in Metastasized Differentiated Thyroid Cancer

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