Side Effects of lapatinib: A Synthesis of Findings from 25 Studies

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Original Abstract of the Article

Major Research Findings

Lapatinib is a targeted therapy drug used to treat HER2-positive breast cancer. Lapatinib works by binding to the HER2 receptor and inhibiting its activity, thereby suppressing cancer cell growth. Several studies have shown that the timing of lapatinib administration affects its tolerability, efficacy, and pharmacokinetics. 15 showed that overnight fasting before lapatinib administration resulted in reduced toxicity compared to nighttime dosing. 18 demonstrated that human induced pluripotent stem cell-derived platelets loaded with lapatinib effectively targeted HER2+ breast cancer metastasis to the brain. This delivery method significantly increased intracellular lapatinib accumulation in brain metastases, inhibited tumor growth, and prolonged survival in tumor-bearing mice. 4 studied the use of T7 peptide-modified pH-sensitive liposomes to encapsulate lapatinib and deliver it to HER2+ breast cancer cells. This method enhanced the drug's accumulation efficiency in tumors, suppressed tumor growth, and reduced side effects. These studies suggest that adjusting lapatinib administration methods can potentially enhance its effectiveness and reduce adverse effects.

Reasons for Side Effects

Lapatinib inhibits HER2 receptors to suppress cancer cell growth. However, HER2 receptors are also found in cells other than cancer cells, such as those in the heart and skin, making lapatinib capable of acting on these cells and causing side effects. 3 suggests that lapatinib can affect the heart and lead to heart failure. 23 indicates that lapatinib can affect the skin, causing skin rashes and nail abnormalities. Additionally, 10 points out that lapatinib can affect the liver, potentially leading to liver dysfunction.

Common Side Effects

Skin

Lapatinib administration can result in skin rashes and nail abnormalities. 23

Heart

Lapatinib administration can lead to heart failure. 3

Liver

Lapatinib administration may cause liver dysfunction. 10

Side Effects Management

Skin

If skin rashes or nail abnormalities occur, consult a doctor. Depending on the severity of the symptoms, lapatinib administration may be discontinued, or medication such as steroids may be prescribed.

Heart

If heart failure symptoms arise, seek immediate medical attention. Heart failure treatment may involve the use of diuretics, ACE inhibitors, or other medications.

Liver

If liver dysfunction symptoms occur, consult a doctor promptly. Liver dysfunction treatment may involve liver protective drugs, steroids, or other medications.

Comparison Across Studies

Commonalities

Lapatinib administration is expected to suppress tumor growth in HER2-positive breast cancer patients. However, lapatinib can affect cells other than cancer cells, including those in the heart, skin, and liver, potentially causing side effects. Overnight fasting before lapatinib administration may reduce side effects. 15

Differences

Different administration methods for lapatinib may lead to varying effectiveness and side effects. 18 demonstrated that delivering lapatinib using human induced pluripotent stem cell-derived platelets effectively targeted HER2+ breast cancer metastasis to the brain, resulting in tumor growth suppression and prolonged survival in tumor-bearing mice. 4 showed that encapsulating lapatinib in T7 peptide-modified pH-sensitive liposomes increased the drug's accumulation efficiency in tumors, suppressed tumor growth, and reduced side effects. These studies suggest that adjusting lapatinib administration methods can potentially enhance its effectiveness and reduce adverse effects.

Precautions for Real-World Application

Lapatinib is a medication used to treat HER2-positive breast cancer. Lapatinib administration should be conducted under the guidance of a medical professional. Consult a doctor immediately if any side effects arise during lapatinib administration.

Limitations of Current Research

Many aspects of the relationship between lapatinib administration methods and side effects remain unclear. Further research is necessary to investigate the potential for adjusting lapatinib administration methods to enhance its effectiveness and reduce side effects.

Future Research Directions

Further research is required to clarify the relationship between lapatinib administration methods and side effects. This research should focus on investigating the potential for adjusting lapatinib administration methods to enhance its effectiveness and reduce side effects.

Conclusion

Lapatinib is a drug effective for treating HER2-positive breast cancer, but it carries a risk of side effects. For safe lapatinib administration, selecting the appropriate administration method under the guidance of a medical professional is crucial.

Literature analysis of 25 papers
Positive Content
24
Neutral Content
0
Negative Content
1
Article Type
2
2
0
8
25
1.

Breast cancer resistance protein (ABCG2) in clinical pharmacokinetics and drug interactions: practical recommendations for clinical victim and perpetrator drug-drug interaction study design.

Author: LeeCaroline A, O'ConnorMeeghan A, RitchieTasha K, GaletinAleksandra, CookJack A, Ragueneau-MajlessiIsabelle, EllensHarma, FengBo, TaubMitchell E, PaineMary F, PolliJoseph W, WareJoseph A, Zamek-GliszczynskiMaciej J

Drug efficacy and safety
Drug-drug interactions

This review discusses the challenges and proposes strategies for conducting clinical drug-drug interaction (DDI) studies that are mediated by breast cancer resistance protein (BCRP). BCRP is a transporter protein involved in drug absorption and excretion. The review recommends specific substrates (sulfasalazine, rosuvastatin) and inhibitors (curcumin, lapatinib) for clinical DDI studies and suggests study design considerations to assess the worst-case scenario.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

2.

Sensitization of HER2 Positive Breast Cancer Cells to Lapatinib Using Plants-Derived Isothiocyanates.

Author: KaczyńskaAngelika, ŚwierczyńskaJoanna, Herman-AntosiewiczAnna

Breast cancer treatment

This in vitro study investigated the potential synergistic effect of combining lapatinib, a HER2 inhibitor, with plant-derived isothiocyanates (sulforaphane, erucin, or sulforaphene) in treating HER2-overexpressing breast cancer cells. The combinations showed synergistic activity, decreasing cell viability and inducing apoptosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Anti-HER2 cancer therapy and cardiotoxicity.

Author: BabarTania, BlombergChristopher, HoffnerEileen, YanXinhua

Breast cancer
Cardiotoxicity

HER2 receptor inhibition has become a significant drug target for breast cancer therapy, with drugs like Trastuzumab showing improved overall survival. However, these drugs are associated with cardiotoxicity, highlighting the crucial role of HER2 in cardiac function. This paper reviews the potential cardiac impact of anti-HER2 therapies and the need for new strategies to mitigate cardiotoxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Repurposing of Benzimidazole Scaffolds for HER2 Positive Breast Cancer Therapy: An <i>In-Silico</i> Approach.

Author: JubieSelvaraj, DuraiUma, LathaSubbiah, AyyamperumalSelvaraj, WadhwaniAshish, PrabhaThangavelu

Anticancer therapy
Speeds up drug development
Side effects

This article discusses the trend of repurposing existing drugs for new applications, particularly in cancer treatment. While many non-cancer drugs have tolerable side effects, their repositioning for anticancer therapy offers a promising strategy for accelerating drug development. Approved drugs are valuable resources for quickly identifying clinically advanced anticancer agents against emerging targets.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

[A case of trastuzumab-resistant breast cancer responding to lapatinib/capecitabine therapy].

Author: HayashiMasanori, OritaMasahiko, HironakaHidehiro, MoritaNobuyoshi

Improved liver metastasis
Paronychia

This case report describes a 56-year-old woman with breast cancer who received multiple lines of chemotherapy. While the initial treatment regimen included trastuzumab and zoledronic acid hydrate, the patient developed bone and liver metastases. After several changes in therapy, lapatinib/capecitabine therapy led to tumor marker normalization and reduction in liver metastasis.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Japanese

8.

HER2-targeted treatment for older patients with breast cancer: An expert position paper from the International Society of Geriatric Oncology.

Author: BrainEtienne, CailletPhilippe, de GlasNienke, BiganzoliLaura, ChengKaris, LagoLissandra Dal, WildiersHans

Adjuvant therapy
HER2-targeted therapy
T-DM1 standard
Trastuzumab alone
Trastuzumab combination
Cardiovascular comorbidity
Drug interactions
Lapatinib side effects
Taxanes difficulty
Toxicity

HER2-positive breast cancer (BC) affects older women, posing challenges due to increased risk of toxicity from therapies. This review provides specific recommendations for treating older patients with HER2+ BC, taking into account their unique needs and risks.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Clinical data mining reveals analgesic effects of lapatinib in cancer patients.

Author: ZhouShuo, ZhengFang, ZhanChang-Guo

Analgesic effect
Drug repurposing

Lapatinib, an FDA-approved cancer drug, was found to be an inhibitor of mPGES-1, a promising target for next-generation anti-inflammatory drugs. This clinical data mining study analyzed pain-related data from 20 randomized clinical trials involving 12,765 patients. The results indicate that lapatinib therapy was associated with a significant reduction in various forms of pain, suggesting it may be repurposed as a novel analgesic.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Hepatotoxicity of Small Molecule Protein Kinase Inhibitors for Cancer.

Author: ViganòMauro, La MiliaMarta, GrassiniMaria Vittoria, PuglieseNicola, De GiorgioMassimo, FagiuoliStefano

Cancer treatment
Hepatotoxicity

Hepatotoxicity is a significant concern with protein kinase inhibitors (PKIs), used to treat cancer. This review discusses the risk and management of hepatotoxicity associated with approved PKIs, emphasizing the need for careful patient evaluation and monitoring.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial.

Author: GossPaul E, SmithIan E, O'ShaughnessyJoyce, EjlertsenBent, KaufmannManfred, BoyleFrances, BuzdarAman U, FumoleauPierre, GradisharWilliam, MartinMiguel, MoyBeverly, Piccart-GebhartMartine, PritchardKathleen I, LindquistDeborah, Chavarri-GuerraYanin, AktanGursel, RappoldErica, WilliamsLisa S, FinkelsteinDianne M,

Improved efficacy

This study investigates the efficacy and safety of adjuvant lapatinib for patients with HER2-positive early-stage breast cancer who have not received trastuzumab, the standard adjuvant treatment.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

A case study of a patient-centered reverse translational systems-based approach to understand adverse event profiles in drug development.

Author: KimSarah, LahuGezim, VakilynejadMajid, SoldatosTheodoros G, JacksonDavid B, LeskoLawrence J, TrameMirjam N

Cardiotoxicity reduction
Mitochondrial dysfunction

This study investigated the molecular causation involved in trastuzumab-induced cardiotoxicity when trastuzumab was combined with other drugs. The study found that the combination of trastuzumab and doxorubicin may synergistically increase cardiotoxicity, while tamoxifen, paroxetine, and lapatinib may diminish cardiotoxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Escalating and de-escalating treatment in HER2-positive early breast cancer.

Author: JoensuuHeikki

Effective breast cancer treatment

This review examines current and emerging therapies for early HER2-positive breast cancer. While 12 months of adjuvant trastuzumab remains the standard, clinical trials are investigating shorter durations, dual HER2 inhibition, and longer treatment courses. Results from these trials are expected to inform future treatment guidelines.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

15.

Overnight fasting before lapatinib administration to breast cancer patients leads to reduced toxicity compared with nighttime dosing: a retrospective cohort study from a randomized clinical trial.

Author: TsudaMoe, IshiguroHiroshi, ToriguchiNaoko, MasudaNorikazu, BandoHiroko, OhgamiMasahiro, HommaMasato, MoritaSatoshi, YamamotoNaohito, KuroiKatsumasa, YanagitaYasuhiro, TakanoToshimi, ShimizuSatoru, ToiMasakazu

Lapatinib efficacy

This study investigated whether lapatinib administration timing is associated with its tolerability, efficacy, and pharmacokinetics.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Tyrosine kinase inhibitors in breast cancer (Review).

Author: IancuGeorge, SerbanDragos, BadiuCristinel Dumitru, TanasescuCiprian, TudosieMihai Silviu, TudorCorneliu, CosteaDaniel Ovidiu, ZguraAnca, IancuRaluca, VasileDanut

Brain penetration
Oral administration
Reduced cardiotoxicity
Adverse side effects
Lack of specificity

Anti-EGFR therapy has shown promise in breast cancer treatment, but most researched agents lack specificity and have frequent side effects. Tyrosine kinase inhibitors (TKIs) have advantages, including reduced cardiotoxicity and oral administration. Lapatinib, neratinib, and pyrotinib are the only TKIs approved for limited indications in a subset of breast cancer patients. Future research should focus on identifying breast cancer subtypes and developing more targeted agents to improve treatment outcomes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

19.

Activity-based kinase profiling of approved tyrosine kinase inhibitors.

Author: KitagawaDaisuke, YokotaKoichi, GoudaMasaki, NarumiYugo, OhmotoHiroshi, NishiwakiEiji, AkitaKensaku, KiriiYasuyuki

Cancer treatment
Drug side effects

This study used activity-based kinase profiling to determine the specificities of nine approved tyrosine kinase inhibitors. The results showed that these inhibitors were well optimized for their target kinases and that activity at particular off-target kinases may contribute to drug side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

20.

Drug induced hypertension--An unappreciated cause of secondary hypertension.

Author: GrossmanAlon, MesserliFranz H, GrossmanEhud

Drug-induced hypertension

Drug-induced hypertension is a less well-known cause of hypertension. Careful evaluation of prescription and non-prescription medications is crucial in the evaluation of hypertensive individuals. Discontinuation of the offending agent will usually achieve adequate blood pressure control.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

21.

Rapid screening of drug candidates against EGFR/HER2 signaling pathway using fluorescence assay.

Author: KhanjaniFarkhondeh, SajediReza H, HasanniaSadegh

Breast cancer treatment

A calcium-based assay using fura-2-AM can effectively screen drug candidates targeting EGFR/HER2 signaling pathways, potentially aiding in the development of new treatments for breast cancer.

Evaluation StudyResearch that systematically evaluates the effectiveness of a particular program or policy. It measures its outcomes and provides important information for future decision-making.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

Lapatinib plus capecitabine for brain metastases in patients with human epidermal growth factor receptor 2-positive advanced breast cancer: a review of the Anatolian Society of Medical Oncology (ASMO) experience.

Author: CetinBulent, BenekliMustafa, OksuzogluBerna, KoralLokman, UlasArife, DaneFaysal, TurkerIbrahim, KaplanMehmet A, KocaDogan, BorubanCem, YilmazBurcak, SevincAlper, BerkVeli, IsıkdoganAbdurrahman, UncuDogan, HarputluogluHakan, CoskunUgur, BuyukberberSuleyman

HER2+ MBC treatment
Lapatinib/capecitabine efficacy

This retrospective evaluation investigated the clinical outcome of patients with HER2+ MBC with BMs treated with lapatinib and capecitabine. The combination therapy was effective and well-tolerated.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

23.

Cutaneous adverse effects of targeted therapies: Part I: Inhibitors of the cellular membrane.

Author: MacdonaldJames B, MacdonaldBrooke, GolitzLoren E, LoRussoPatricia, SekulicAleksandar

Cancer treatment
Skin toxicity

This article explores the cutaneous adverse effects associated with targeted agents used in oncology. These agents, while offering novel mechanisms of action and potential for personalized medicine, often cause skin-related toxicities that can be dose-limiting or lead to treatment discontinuation. The article emphasizes the importance of dermatologists understanding and recognizing these toxicities to provide effective clinical management.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

24.

Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with breast cancer treated with HER2 blockade.

Author: WuJunyan, QiuKaifeng, ZhuJianhong, LiJianfang, LinYin, HeZhichao, LiGuocheng

No increased risk of FAEs

This meta-analysis found that the addition of HER2 blockades to treatment regimens for breast cancer did not significantly increase the risk of fatal adverse events compared with control.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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