Photosensitive rash due to the epidermal growth factor receptor inhibitor erlotinib

Luu, Minnelly; Lai, Susan; Patel, Jyoti D.; Guitart, Joan; Lacouture, Mario E.

doi:10.1111/j.1600-0781.2007.00273.x

Cited by 46 publications

(23 citation statements)

References 7 publications

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“…Interestingly, the incidence and severity of the skin toxicity have been consistently found to be associated with increased tumor response rate and longer survival when analyzed in the context of well-controlled trials (24)(25)(26)(27)(28)(29). The reasons for such association are unclear and several hypotheses, attributing either a predictive or prognostic role to the skin toxicity, have been proposed but none of them has been proved (12,13,30,31).…”

Section: Introductionmentioning

confidence: 99%

The Phosphatase Inhibitor Menadione (Vitamin K3) Protects Cells from EGFR Inhibition by Erlotinib and Cetuximab

Pérez-Soler

Zou

et al. 2011

Clinical Cancer Research

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Purpose: Skin toxicity is the main side effect of epidermal growth factor receptor (EGFR) inhibitors, often leading to dose reduction or discontinuation. We hypothesized that phosphatase inhibition in the skin keratinocytes may prevent receptor dephosphorylation caused by EGFR inhibitors and be used as a new potential strategy for the prevention or treatment of this side effect.Experimental Design: Menadione (Vitamin K3) was used as the prototype compound to test our hypothesis. HaCat human skin keratinocyte cells and A431 human squamous carcinoma cells were used. EGFR inhibition was measured by Western blotting and immunofluorescence. Phosphatase inhibition and reactive oxygen species (ROS) generation were measured by standard ELISA and fluorescence assays.Results: Menadione caused significant and reversible EGFR activation in a dose-dependent manner starting at nontoxic concentrations. EGFR activation by menadione was associated with reversible protein tyrosine phosphatase inhibition, which seemed to be mediated by ROS generation as exposure to antioxidants prevented both menadione-induced ROS generation and phosphatase inhibition. Short-term coincubation of cells with nontoxic concentrations of menadione and the EGFR inhibitors erlotinib or cetuximab prevented EGFR dephosphorylation. Seventy-two-hour coincubation of cells with the highest nontoxic concentration of menadione and erlotinib provided for a fourfold cell growth inhibitory protection in HaCat human keratinocyte cells.Conclusions: Menadione at nontoxic concentrations causes EGFR activation and prevents EGFR dephosphorylation by erlotinib and cetuximab. This effect seems to be mediated by ROS generation and secondary phosphatase inhibition. Mild oxidative stress in skin keratinocytes by topical menadione may protect the skin from the toxicity secondary to EGFR inhibitors without causing cytotoxicity. Clin Cancer Res; 17(21); 6766-77. Ó2011 AACR.

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Section: Introductionmentioning

confidence: 99%

The Phosphatase Inhibitor Menadione (Vitamin K3) Protects Cells from EGFR Inhibition by Erlotinib and Cetuximab

Pérez-Soler

Zou

et al. 2011

Clinical Cancer Research

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“…Members of the NCCTG observed that previous reports had described that EGFR inhibitor-induced rashes were exacerbated by sunlight. In particular, Luu et al [ 21 ] described a 75-year-old man who developed a rash from erlotinib only on unprotected areas, whereas sun-protected areas manifested no rash. Such observations suggested that an agent such as sunscreen might play a role in preventing or attenuating the severity of the EGFR inhibitor-induced rash.…”

Section: Treatment Of Egfr Inhibitor-induced Rashmentioning

confidence: 98%

Rash from EGFR inhibitors: Opportunities and challenges for palliation

Solomon

Jatoi

2008

Curr Oncol Rep

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“…Some patients receiving EGFR-targeted agents have been reported to show widespread erythema, infiltration and pustules in sun-exposed areas 19,53,54. One randomized study, N05C4, conducted in the US by NCCTG, has investigated the prophylactic use of SPF60 sunscreen in cancer patients receiving an EGFR-targeted agent as part of their therapy 39…”

Section: Resultsmentioning

confidence: 99%

A review of the treatment options for skin rash induced by EGFR-targeted therapies: Evidence from randomized clinical trials and a metaanalysis

Ocvirk¹,

Heeger²,

McCloud³

et al. 2013

Radiology and Oncology

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BackgroundAgents targeting the epidermal growth factor receptor (EGFR) are amongst the most extensively used of the targeted agents in the therapy of some of the most common solid tumors. Although they avoid many of the classic side effects associated with cytotoxic chemotherapy, they are associated with unpleasant cutaneous toxicities which can affect treatment compliance and impinge on patient quality of life. To date, despite a plethora of consensus recommendations, expert opinions and reviews, there is a paucity of evidence-based guidance for the management of the skin rash that occurs in the treatment of patients receiving EGFR-targeted therapies.MethodsA literature search was conducted as a first step towards investigating not only an evidence-based approach to the management of skin rash, but also with a view to designing future randomized trials.ResultsThe literature search identified seven randomized trials and a meta-analysis was conducted using the data from four of these trials involving oral antibiotics. The meta-analysis of the data from these four trials suggests that prophylactic antibiotics might reduce the relative risk of severe rash associated with EGFR-targeted agents by 42–77%. Vitamin K cream was also identified as having a potential role in the management EGFR-targeted agent induced rash.ConclusionsThis review and meta-analysis clearly identify the need for further randomized studies of the role of oral antibiotics in this setting. The results of the ongoing randomized trials of the topical application of vitamin K cream plus or minus doxycycline and employing prophylactic versus reactive strategies are eagerly awaited.

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Photosensitive rash due to the epidermal growth factor receptor inhibitor erlotinib

Cited by 46 publications

References 7 publications

The Phosphatase Inhibitor Menadione (Vitamin K3) Protects Cells from EGFR Inhibition by Erlotinib and Cetuximab

The Phosphatase Inhibitor Menadione (Vitamin K3) Protects Cells from EGFR Inhibition by Erlotinib and Cetuximab

Rash from EGFR inhibitors: Opportunities and challenges for palliation

A review of the treatment options for skin rash induced by EGFR-targeted therapies: Evidence from randomized clinical trials and a metaanalysis

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