Analysis of dermatologic events in patients with cancer treated with lapatinib

Lacouture, Mario E.; Laabs, S.; Koehler, Maria; Sweetman, Robert; Preston, A.; Leo, Angelo Di; Gómez, Henry L.; Salazar, Vanessa; Byrne, Julie; Koch, Kevin M.; Blackwell, K. L.

doi:10.1007/s10549-008-0020-7

Cited by 80 publications

(44 citation statements)

References 22 publications

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“…The most common grade 3-4 toxicities included diarrhea, seen in 18.2% of subjects, all grade 3; rash, seen in 13.6%, all grade 3; and infection, seen in 15.9% (6 grade 3, 1 grade 4). Hand-foot syndrome occurred in 18.2% of subjects, all grade 1-2. Mucositis occurred in 31.8% of subjects and was grade 3-4 in 9.1%.…”

Section: Accepted Articlementioning

confidence: 95%

“…In a phase III study of this combination for metastatic breast cancer, cardiac effects were rare and recovery to baseline LVEF was the norm [18]. As a precaution, the following will be reported as a SAE:…”

Section: Expected Adverse Events 511 Cardiac Dysfunctionmentioning

confidence: 99%

“…5.1.2 Gastrointestinal: 65% of patients in the capecitabine plus lapatinib group of the phase III breast cancer study [18] experienced diarrhea [18] with 13% of these grade three and one percent grade four. 44% experienced nausea with 2% of these grade three and no grade four events.…”

Section: Version 3/8/2011mentioning

confidence: 99%

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Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

Weiss

Bagley

Hwang

et al. 2016

Cancer

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Funding: GSK (subsequently Novartis) funded this study. There are no NIH grants related to this work.COI: RBC has served as a consultant to GSK. CJL has served as a consultant to Novartis. The remaining authors report no COIs directly related to this work. Précis:Patients with first line recurrent/metastatic head and neck cancer were treated with the all-oral regimen capecitabine and lapatinib. mPFS was 4.2 months and mOS was 10.7 months. Keywords: head and neck neoplasms, capecitabine, lapatinib Page 2 of 72 CancerThis article is protected by copyright. All rights reserved. Accepted Article Abstract:Background: Combination of cisplatin, 5FU and cetuximab is a standard treatment for recurrent/metastatic head and neck cancer with a high rate of toxicity.Identifying less toxic, equally effective regimens is imperative. We therefore investigated first-line treatment with an all-oral regimen of capecitabine and lapatinib.Materials and Methods: Patients were required to have incurable head and neck cancer of any primary site other than nasopharynx, PS0-2, and no prior exposure to capecitabine or lapatinib. Subjects were treated with capecitabine 1000mg/m 2 BID and lapatinib 1250mg daily. Capecitabine was administered for 14 of 21 days for 4 cycles. Lapatinib was administered daily until progression. The primary outcome was overall survival (OS).Results: 44 subjects were accrued between 11/13/2009 and 4/29/2014. Patients with PS0 were 38.6% of the sample, PS1 52.3%, and PS2 9.1%. 81.8% were male and the median age was 62 years. Prior attempts at curative treatment with chemotherapy had been utilized in 68.2% of patients (platinum used in 55.8%).There was no grade 5 toxicity. The most common adverse events were diarrhea (18.2% G3) and rash (13.6% G3). The primary objective was met; OS was 10.7 months (90% CI 8.7 to 12.9). Overall response rate was 25% (90% CI: 15%-38%).PFS was 4.2 months (90% CI 3.6 to 5.1). Results were not substantially different when subdivided by p16 status. Only two patients were positive for HER2 by IHC.Conclusions: The study met its primary objective of survival comparable to the EXTREME regimen and toxicity of this all-oral regimen was tolerable. Page 3 of 72 CancerThis article is protected by copyright. All rights reserved. Accepted Article Introduction:Recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) remains incurable in the vast majority of cases. Cisplatin-containing regimens have been the standard treatment platform for more than 2 decades. The most recent advance was the addition of cetuximab to a cis-or carboplatin-containing regimen, which increased overall survival from 7.4 to 10.1 months compared to chemotherapy alone [1]. The EXTREME regimen represented the first significant breakthrough in the treatment of R/M HNSCC, but it came at a price. Adverse events in both arms of the EXTREME trial were significant; 76% of patients receiving 5FU and platinum experienced grade 3-4 adverse events, and 82% of patients receiving cisplatin, 5FU, and cetuximab experienced grade 3...

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Section: Accepted Articlementioning

confidence: 95%

Section: Expected Adverse Events 511 Cardiac Dysfunctionmentioning

confidence: 99%

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Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

Weiss

Bagley

Hwang

et al. 2016

Cancer

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“…Дерматологические НЯ, такие как папуло-пустулезная (угревая) сыпь, зуд, сухость/трещины кожи, алопеция, гипертрихоз и паронихия, описывались у онкологических больных, получавших ИТК-EGFR [29]. В клинических иссле-дованиях ИТК-EGFR III фазы у 54-89% пациентов наблю-дались кожные НЯ любой степени и 0-16,2% -НЯ ≥ 3 степени [29][30][31][32][33][34][35][36][37][38][39][40][41]. Критерии NCI-CTCAE являются стандар-том классификации и методом оценки степени тяжести, широко используемым всем онкологическим сообществом при описании НЯ в клинических исследованиях терапии рака.…”

Section: дерматологические нежелательные явленияunclassified

“…Ксероз был основным НЯ у всех пациентов, который в 25% случаев был умеренным или тяжелым (2 или 3 степени) [33,34]. Аналогичным образом у пациенток с метастатическим раком молочной железы комбинация лапатиниба и капе-цитабина ассоциировалась с сыпью у 13% пациентов, при этом у 50% пациентов сыпь развивалась на фоне лечения лапатинибом в комбинации с паклитакселом [35].…”

Section: таблица 1 частота снижения/модификации дозы и прекращения лunclassified

Algorithms for Management of Patients With Adverse Events on Therapy With Tyrosine Kinase Inhibitors Egfr

Сакаева¹

2017

Med. sov.

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С емейство рецепторов ErbB является одной из наиболее широко изученных систем передачи сигналов [1]. Семейство ErbB включает четыре мембранно-связанных структурно родственных рецепто-ра тирозинкиназы: рецептор EGF (EGFR; также известен как ErbB1), HER2 (ErbB2), ErbB3 и ErbB4 [2]. Путь ErbB является одной из наиболее широко изученных систем передачи сигналов, вовлеченных в функционирование нормальных клеток, и при некоторых типах рака [1]. Нарушение регуляции активности рецепторов семейства ErbB и нисходящих сигнальных путей связано с развити-ем некоторых опухолей у человека.Механизм активации передачи сигналов ErbB зависит от лиганд-индуцированной стабильности гомо-или гете-родимеров, образованных различными тирозинкиназами рецепторов семейства ErbB [3]. Рецепторы семейства ErbB являются клинически доказанными мишенями для новых противоопухолевых препаратов [4][5][6][7].Ингибиторы EGFR показаны для лечения колорек-тального рака (панитумумаб, цетуксимаб), немелкокле-точного рака легкого (гефитиниб, эрлотиниб, афатиниб), плоскоклеточного рака головы и шеи (цетуксимаб), рака поджелудочной железы (эрлотиниб).В отличие от цитотоксической химиотерапии, лечение ингибиторами EGFR сопровождается минимальными неспеци фическими и гематологическими побочными эффектами.Активирующие мутации гена рецептора EGFR явля-ются наиболее значимыми предикторами ответа на ингибиторы тирозинкиназы EGFR (ИТК-EGFR) гефити- Ключевые слова: местнораспространенный и метастатический немелкоклеточный рак легкого, ингибиторы тирозин-киназы EGFR, терапия, нежелательные явления. D.D. SAKAEVA, MD, Prof., Republican Oncologic Dispensary of the Ministry of Health of the Republic of Bashkortostan, Ufa ALGORITHMS FOR MANAGEMENT OF PATIENTS WITH ADVERSE EVENTS ON THERAPY WITH TYROSINE KINASE INHIBITORS EGFRThe tyrosine kinase inhibitors (TKIs) of the epidermal receptor growth factor (EGFR) such as gefitinib, erlotinib and afatinib, are the standard first-line therapy in locally advanced and metastatic non-small cell lung cancer (NSCLC) with frequent mutations of the EGFR gene. These drugs are more effective from the point of view of frequency response (FR) and survival without progression (SWP), less toxic and better tolerated than the standard two-component chemotherapy based on platinum drugs. The most frequent adverse events (AE) are gastrointestinal (GI) (diarrhea and stomatitis/mucositis) and dermatological (rash, dry skin and paronychia). They are usually mild, but in some cases symptoms can be moderate and more severity and have a negative impact on quality of life (QOL) of the patient and can require dose adjustment or discontinuation of treatment. Management of AEs, including preventive measures, supportive therapy, temporary cancellation and a reduction in the dose of the drug is important. Recommendations for the prevention and treatment of dermatological toxicity (rash, dry skin and paronychia) and toxicity for the gastrointestinal tract (diarrhoea, stomatitis and mucositis) related to therapy TKI-EGFR are developed. These guidelines descri...

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Capecitabine-Induced Hand-Foot Syndrome Complicated by Pseudomonal Superinfection Resulting in Bacterial Sepsis and Death

Hoesly¹

2011

Arch Dermatol

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Background: Hand-foot syndrome (HFS) is a relatively common dermatologic toxic reaction to certain anticancer therapies. Although not life-threatening, this complication can reduce patient quality of life. Dose modification of the inciting agent serves as the most effective management of HFS, although a variety of anecdotal reports suggest that other agents may also be efficacious. We present the first reported case of fatal HFS (to our knowledge) and provide a comprehensive review of this condition.Observations: A 61-year-old woman with metastatic breast cancer who was undergoing treatment with capecitabine developed erythema, fissuring, and erosions over both hands and feet, consistent with HFS. Pseudomonal superinfection leading to bacterial sepsis and death rapidly ensued.Conclusions: Although HFS is widely regarded as a nonlife-threatening toxic reaction to cancer treatment, our case demonstrates that infectious complications of this condition can prove fatal. Prevention, early recognition, and implementation of various management strategies for HFS and its infectious complications are important in optimizing patient quality of life and minimizing unfavorable outcomes.

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Analysis of dermatologic events in patients with cancer treated with lapatinib

Abstract: Most DEs in lapatinib-treated patients present early, are mild to moderate in severity, and infrequently require dose modification or treatment interruption. Lapatinib-associated DEs appear to differ clinically from those associated with EGFR TKIs in both frequency and severity.

Cited by 80 publications

References 22 publications

Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

Capecitabine and lapatinib for the first‐line treatment of metastatic/recurrent head and neck squamous cell carcinoma

Algorithms for Management of Patients With Adverse Events on Therapy With Tyrosine Kinase Inhibitors Egfr

Capecitabine-Induced Hand-Foot Syndrome Complicated by Pseudomonal Superinfection Resulting in Bacterial Sepsis and Death

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