Safety Profile and Clinical Recommendations for the Use of Lapatinib

Chatsiproios, D.

doi:10.1159/000285776

Cited by 11 publications

(8 citation statements)

References 20 publications

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“…However, the general guidance for the management of diarrhea during cancer chemotherapy may be employed in this circumstance . Likewise, guidelines for the treatment of diarrhea induced by specific anticancer agents (e.g., lapatinib) could also be used . As diarrhea might to some extent be caused by an exocrine pancreatic insufficiency, medical replacement of pancrelipase should be considered, particularly in patients who report fatty stools and bowel movements during the meal or shortly afterwards .…”

Section: Resultsmentioning

confidence: 99%

Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma

Schmidinger

Danesi

2017

The Oncologist

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Cabozantinib leads to improved survival outcomes in renal cell carcinoma patients compared with everolimus. However, management of the adverse event profile is crucial to achieve optimum adherence and outcomes with the use of cabozantinib. This review aims to provide appropriate guidance that will minimize the impact of adverse events and help to maximize the utility of this agent in patients with advanced renal cell carcinoma.

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Section: Resultsmentioning

confidence: 99%

Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma

Schmidinger

Danesi

2017

The Oncologist

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“…Yet, while effective, the interaction of different agents in combination therapies may add further toxicities and may require a more careful management. Lapatinib for example, although generally considered well tolerated, can lead to gastrointestinal side effects such as diarrhea, nausea and vomiting that can result in weight loss, skin rash and fatigue, which, in the long-run can affect the quality of life of patients [ 10 ] [ 35 ]. Hence, means to potentiate lapatinib efficacy while improving its tolerability would be highly desirable in the clinic.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, lapatinb works better when combined with other inhibitors of key pathways in melanoma, such as γ-secretase inhibitors [ 3 ], and BRAF inhibitors [ 8 ], highlighting a cooperation among different pathways in melanoma pathogenesis. Additionally, although generally considered well tolerated, lapatinib can lead to gastrointestinal side effects such as diarrhea, nausea and vomiting that can result in some weight loss, skin rash and fatigue [ 10 ]. Hence, means to potentiate its effectiveness while improving its tolerability would be highly desirable.…”

Section: Introductionmentioning

confidence: 99%

The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition

Thakur

Roscilli³

et al. 2017

Oncotarget

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Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U. pinnatifida is integrated into the treatment regimen. Fucoidan not only enhances tumor growth inhibition, it counteracts the morbidity associated with prolonged lapatinib treatment. Fucoidan doubles the cell killing capacity of lapatinib. These effects are associated with a further decrease in AKT and NFκB signaling, two key pathways involved in melanoma cell survival. Importantly, the enhancing cell killing effects of fucoidan can be recapitulated by inhibiting ERBB3 by either a specific shRNA or a novel, selective ERBB3 neutralizing antibody, reiterating the key roles played by this receptor in melanoma. We therefore propose the use of lapatinib or specific ERBB inhibitors, in combination with fucoidan as a new treatment of melanoma that potentiates the effects of the inhibitors while protecting from their potential side effects.

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“…Lapatinib shares the ERbB2 target with monoclonal antibody trastuzumab, and literature suggests that both show LVEF declines in patients. 46 Accordingly, monitoring guidelines have been proposed. The Cardiac Guidelines Consensus Committee recommends a baseline LVEF of ≥50% to initiate treatment, with follow-up evaluations via echocardiogram or multigated acquisition scan one to two times during therapy and at the end of treatment.…”

Section: Selected Tkismentioning

confidence: 99%

“…An increase in these biomarkers would also warrant referral to a cardiologist. 46 The product labeling includes warnings for LVEF decline and QT prolongation and suggests monitoring in line with these guidelines, with a detailed collection of past medical history.…”

Section: Selected Tkismentioning

confidence: 99%

Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated cardiovascular toxicities

Chaar

Kamta

Ait‐Oudhia

2018

OTT

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The tyrosine kinase inhibitor (TKI) drug class is a prominently used option in the treatment of various cancers. Safety evaluation of these drugs has shown evidence of cardiotoxicity of varying frequency and severity between agents; concern has led to updated labeling, warning prescribers of such. This review seeks to clarify the present dangers and investigate cardiotoxic mechanisms of action for each discussed TKI. Dasatinib was connected primarily with an incidence of fluid retention, edema, QT prolongation, and pulmonary hypertension in clinical studies. It is theorized that this is due to a combination of off-target kinase binding and on-target binding of Bcr-Abl, and less likely, mitochondrial induced apoptosis. Studies showed sorafenib to carry the risk of hypertension, QT prolongation, and myocardial infarction. Proposed mechanisms for these side effects include inhibition of proteins, vascular endothelium growth factor receptor, hERG potassium channels, and the RAF/MERK/ERK pro-survival pathway. Finally, lapatinib showed evidence of decreased left ventricular ejection fraction (LVEF) and QT prolongation in clinical studies. The literature attributes these as side effects of on-target ErbB2 binding leading to mitochondrial induced apoptosis. The concern warranted by these findings is in question. Pooled safety data suggest that the overall risk for cardiotoxicity is minimal in dasatinib and lapatinib. Sorafenib seems to carry a moderate concern. For the discussed agents, recommendations agree that routine monitoring via methods such as electroencephalogram, cardiac biomarkers, and blood pressure is warranted during the course of treatment, in addition to a comprehensive collection of past medical history and risk factors to identify those at heightened risk for cardiovascular events.

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Safety Profile and Clinical Recommendations for the Use of Lapatinib

Cited by 11 publications

References 20 publications

Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma

Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma

The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition

Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated cardiovascular toxicities

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