New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

Aparicio-Gallego, Guadalupe; Blanco, Miguel; Figueroa, Angélica; García‐Campelo, Rosario; Valladares‐Ayerbes, Manuel; Grande-Pulido, Enrique; Antón-Aparicio, Luis

doi:10.1158/1535-7163.mct-10-1124

Cited by 102 publications

(72 citation statements)

References 70 publications

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“…Sunitinib is an oral inhibitor of different tyrosine kinases, such as VEGFR and platelet-derived growth factor receptor (PDGFR), the stem cell factor KIT receptor, the fms-like tyrosine kinase 3 (FLT3) receptor, and the protein product of the RET oncogene , Mendel et al 2003, O'Farrell et al 2003, Wilhelm et al 2004, Faivre et al 2007, Sulkes 2010, Aparicio-Gallego et al 2011. Sunitinib is approved for the first-line treatment of mRCC (Table 1; Demetri et al 2006, Motzer et al 2006, Goodman et al 2007, Mannavola et al 2007, Wolter et al 2008, Ljungberg et al 2010, Di Lorenzo et al 2011, Fratto et al 2011, Castellano et al 2013.…”

Section: Introductionmentioning

confidence: 99%

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Bianchi¹,

Rossi²,

Tomao³

et al. 2013

Endocrine-Related Cancer

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The most recent World Health Organization classification of renal neoplasms encompassed nearly 50 distinctive renal neoplasms. Different histological subtypes have different clinical outcomes and show different responses to therapy. Overall, the incidence of kidney cancer has increased worldwide in the last years. Although the most common type of kidney cancer is localized renal cell carcinoma (RCC), with a 5-year survival rate of 85%, about one third of patients present advanced or metastatic disease at diagnosis, with a 5-year survival rate of only 10%. Multi-targeted receptor tyrosine kinase inhibitors (TKIs, sunitinib and sorafenib), the anti-VEGF MAB bevacizumab in association with interferon-a, and the mTOR inhibitors are now approved for the treatment of mRCC. Recently, the novel agents pazopanib and axitinib have also demonstrated efficacy in mRCC patients. Several recent retrospective and prospective trials have suggested that some of their adverse events, such as hypertension, hypothyroidism, and hand foot syndrome (HFS) may act as potential biomarkers of response and efficacy of treatment. In this review, we analyzed the studies that have suggested a relationship between hypothyroidism onset and a better outcome of mRCC patients treated with TKIs. The biological mechanisms suggesting and explaining this correlation are not well known and different speculative theories have been considered in order to investigate the clinical link between hypothyroidism occurrence and the prolonged therapy with TKIs in solid tumors. Furthermore, the management of this unexplained side effect is very important to maximize the efficacy of therapy in mRCC patients because there is a clear and consistent relationship between drug dose and efficacy of treatment. Certainly, other studies are needed to clarify whether a better outcome is associated with hypothyroidism induced to TKIs in patients with mRCC.

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Section: Introductionmentioning

confidence: 99%

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Bianchi¹,

Rossi²,

Tomao³

et al. 2013

Endocrine-Related Cancer

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“…The assessment of AEs should comprehend severity scales like the common terminology criteria for AEs since this may help to assist in treatment reductions/withdrawals [39]. Table 2 describes the most common AEs and strategies to manage them [11,[40][41][42][43][44][45].…”

Section: Aes and Toxicitiesmentioning

confidence: 99%

Novel therapies against aggressive differentiated thyroid carcinomas

Donato¹,

Santos

Simões

et al. 2018

International Journal of Endocrine Oncology

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The incidence of thyroid cancer (TC) is increasing. Although the majority of these cancers have a good prognosis, 10% of these will develop local recurrence and/or distant metastases. Conventional cytotoxic chemotherapy has been largely replaced by molecular-target therapies, but it can still have a role. Two tyrosine kinase inhibitors have been approved for the treatment of advanced differentiated TC. They significantly improve progression-free survival, but at the cost of frequent and potentially serious adverse effects. At the moment, there are multiple clinical trials with other tyrosine kinase inhibitors and other drugs. We present a review of the current standard of care and what is up to come in the treatment of advanced TC.

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“…hypothyroidism, anaemia, depression, malnutrition, distress, sleep disorders, pain) and provide medical treatment as necessary Provide counselling on how to cope with fatigue and provide motivation to succeed during therapy Deliver strategies to support the adaptation of daily activities to conserve energy In patients with reduced QoL, consider reducing the sunitinib dose Neutropenia Treatment can continue if severity is less than grade 3 For severe neutropenia, treatment should be interrupted until toxicity decreases and should be permanently discontinued if symptoms recur [Novartis Pharmaceuticals Corporation, 2012;Pfizer Inc., 2011;Moldawer and Wood, 2010;Balagula et al 2012;Ferte et al 2011;de Oliveira et al 2011;Boers-Doets et al 2011;White et al 2010;Rodriguez-Pascual et al 2010;Nathan et al 2009;Grunwald et al 2010;Cohen and Oudard, 2012;Ravaud, 2011;Di Lorenzo et al 2011;Eisen et al 2012;Bhojani et al 2008;Aparicio-Gallego et al 2011]. ACE, angiotensin-converting enzyme; QoL, quality of life.…”

Section: Everolimusmentioning

confidence: 99%

The use of targeted therapies in pancreatic neuroendocrine tumours: patient assessment, treatment administration, and management of adverse events

Cummins

Pavlakis

2013

Ther Adv Med Oncol

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Abstract:Together with the use of novel oral targeted therapies, a multidisciplinary approach can be used to effectively treat patients with advanced pancreatic neuroendocrine tumours (pNETs). Here we review the integration of the oncology nurse to the newly developed oral treatment setting for patients with pNETs. From the outset, the nurse must be involved in various processes, including performance of baseline assessments (e.g. blood pathology, cardiac and lung function testing, patient history) and general medical observations, treatment administration, dietary guidance, evaluation of comorbidities, and review of concomitant medications. Patient education and establishment of a strong partnership in care before the start of pNET therapy ultimately increase treatment adherence and reduce potential toxicities. Regular review of general patient status and disease progression and continuous monitoring of adverse events also help enhance treatment outcomes and subsequently improve quality of life. Nurses' knowledge of agent-specific toxicities and prompt, proactive management is a critical aspect of care. In essence, as the pNET treatment landscape evolves, the role of the healthcare professional in overall patient care must shift accordingly.

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New Insights into Molecular Mechanisms of Sunitinib-Associated Side Effects

Cited by 102 publications

References 70 publications

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Thyroid dysfunction and tyrosine kinase inhibitors in renal cell carcinoma

Novel therapies against aggressive differentiated thyroid carcinomas

The use of targeted therapies in pancreatic neuroendocrine tumours: patient assessment, treatment administration, and management of adverse events

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