Efficient Prevention Strategy against the Development of a Palmar-Plantar Erythrodysesthesia during Chemotherapy

Lademann, Juergen; Martschick, Anja; Kluschke, Franziska; Richter, Heike; Fluhr, Joachim W.; Patzelt, Alexa; Jung, Sora; Chekerov, Radoslav; Darvin, Maxim E.; Haas, Norbert; Sterry, Wolfram; Zastrow, L.; Sehouli, Jalid

doi:10.1159/000351801

Cited by 21 publications

(24 citation statements)

References 19 publications

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“…Therefore, a combined prevention strategy is recommended consisting of adequate behavioral measures and application of an antioxidant-containing cream providing a high RPF during the entire period of chemotherapeutic treatment. The efficiency of oral or topical antioxidant substances in the treatment of PPE has been shown in previous studies [3,21,23,24] favoring the assumption of a pathomechanism based on the topical formation of free radicals in the skin after excretion of the chemotherapeutic agent [18,19]. The high RPF and the continuous topical application of ointment enhance the antioxidant efficiency at the site of application.…”

Section: Resultsmentioning

confidence: 92%

“…The high RPF and the continuous topical application of ointment enhance the antioxidant efficiency at the site of application. Topical ointment not only leads to immediate neutralization of free radicals but also serves as a protective film impeding the accumulation of the chemotherapeutic agent in the stratum corneum [3,19,21,25]. Since topical antioxidant application in PPE patients has been investigated only recently, the available data is limited.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, Lademann et al [3,21 ]showed that continuous local application of an ointment containing highly concentrated antioxidants exhibiting a radical protection factor of at least 4,000 (patent WO 2008023064 A2) is an effective prevention strategy against PPE providing even therapeutic effects.…”

Section: Introductionmentioning

confidence: 99%

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Influence of Mechanical Stress on Palmoplantar Erythrodysesthesia - a Case Report

Jung

Sehouli²,

Patzelt³

et al. 2015

Oncol Res Treat

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Background: Cutaneous adverse events can have an important negative influence on quality of life and compliance in affected patients. Palmoplantar erythrodysesthesia (PPE; hand-foot syndrome) is a cutaneous toxicity associated with chemotherapeutic treatment, which necessitates treatment interruption or dose reduction in severe cases. This case report of pegylated liposomal doxorubicin-induced PPE shows the influence of mechanical stress on the development of skin lesions in various locations and the importance of patient education and compliance. Case Report: We present the case of a 43-year-old female patient diagnosed with ovarian cancer and having undergone surgical and chemotherapeutic treatment. The development of extensive grade 3 PPE affecting numerous areas of the body particularly exposed to mechanical pressure necessitated dermatological treatment. The combination of local application of an antioxidant-containing ointment and the patient's compliance made it possible to continue chemotherapy without interruption or dose reduction. Conclusion: The development of PPE often limits the use of chemotherapeutic agents, and this case report can provide a possible therapeutic and preventive strategy for affected patients.

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

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Influence of Mechanical Stress on Palmoplantar Erythrodysesthesia - a Case Report

Jung

Sehouli²,

Patzelt³

et al. 2015

Oncol Res Treat

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“…This theory is underlined by pre-clinic data using new optical methods directly measuring fluorescent agents in the skin. However, the prophylactic and therapeutic effect of antioxidants on HFSR only could be observed within a small count of studies with a limited number of patients [22,23]. A head to head comparison of Mapisal with the empirically used urea cream could not confirm the theory.…”

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confidence: 92%

Strategies for Prevention and Treatment of Chemotherapy-Induced Hand-Foot- Skin-Reaction (HFSR)

Gencer¹,

Hofheinz²

2016

J Clin Exp Dermatol Res

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DescriptionHand-foot-skin-reaction (HFSR), also known as palmoplantar erythrodysesthesia, is a frequently occurring side effect of many antineoplastic therapies. Interruption, dose reduction or even discontinuation of anti-tumor therapy due to missing strategies in prevention or treatment of HFSR can be the consequence. According to severity grade of HFSR restrictions in activities of daily life can occur, which can lead to an impairment of quality of life (QOL). Especially skin-related QOL, which actually can be assessed by a variety of different questionnaires, often decreases when HFSR occurs, which can be underlined by some lately published investigations. Nardone and coworkers used the skindex-16 questionnaire to measure the skin-related QOL of patients treated with sunitinib and sorafenib. Patients with higher grades of HFSR showed lower results in the symptoms and emotions scores of the skindex-16 [1]. Chan et al. report in a lately published review that CTCAE grading of HFSR seems to correlate well with skin-related QOL, irrespective of the available questionnaires used for assessment [2].Main agents potentially causing HFSR are tyrosine kinase inhibitors such as sorafenib, sunitinib or regorafenib as well as cytostatic agents like pegylated liposomal doxorubicin (PLD), taxanes and pyrimidine analogues (infusional 5-Fluorouracil or capecitabine). The overall incidence rate of HFSR differs from 20% to 60%, depending on trialdesigns and analyzed anti-cancer drugs [3][4][5][6][7][8].The pathomechanism of HFSR actually seems not to be sufficiently explained. Almost 20 years ago the observed skin reaction in patients treated with a high-dosed chemotherapy led to one of the leading theories for development of HFSR [9]. According to this theory, toxic active metabolites resulting from the applied chemotherapy were eliminated over the eccrine sweat glands of the skin and caused severe damage. Especially at the palms of the hands and the planta of the feet as well as intertrigineous areas the count of sweat glands is highest in human body. Additionally, the thick stratum corneum of the skin in these areas serves as a reservoir for the toxic metabolites leading to severe skin reaction. Recently, other potential pathomechanism were suggested by Lademann and coworkers. New optical methods were used to detect fluorescent substances such as anthracyclines on the skin surface and around the sweat glands during or after administration [10]. As a consequence the excretion of toxic metabolites over the sweat glands results in formation of free radicals and hence in damaging cellular components. Thus, a prevention of HFSR using antioxidant agents seemed reasonable.PROCAPP, an open label randomized phase III trial was conducted to compare the prophylactic effect of Mapisal and urea-cream in patients receiving capecitabine therapy [11]. Mapisal is a medical device containing a huge variety of antioxidants and other nourishing ingredients. Patients with gastrointestinal or breast cancer not pretreated with tyrosine kinase inh...

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“…As prevention strategy, recently, an antioxidant-containing ointment with a high radical protection factor (RPF) [17] was developed which neutralizes the free radicals before they can start their destructive action. In a pilot study on 20 patients who were suffering from ovarian carcinoma and were treated with PLD (40 mg/m 2 ) [18], it was found that the antioxidant-containing ointment not only represented an effective prevention strategy against the development of PPE, but showed a good therapeutic effect even if a PPE already existed. These promising results encouraged us to use the ointment also for the treatment of patients under other chemotherapeutic agents than PLD, who had developed inflammatory dermal side effects.…”

Section: Introductionmentioning

confidence: 99%

Palmoplantar Erythrodysesthesia-Like Skin Symptoms in Patients under Various Chemotherapeutics: Preventive and Therapeutic Options

Lademann

Röwert‐Huber²,

Haas

et al. 2014

Skin Pharmacol Physiol

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Background/Aims: The palmoplantar erythrodysaesthesia (PPE) is an inflammatory cutaneous side effect in patients under chemotherapy with pegylated liposomal doxorubicin (PLD), with indications that also other chemotherapeutics induce similar side effects. Recently, it has been demonstrated that PLD escapes with the sweat onto the skin inducing radical-forming processes that damage the skin. The topical application of antioxidants with a high radical protection factor has proven to be a very efficient prevention strategy for PLD-treated patients. Methods: 68 patients, who had been treated with 12 different chemotherapeutics and experienced side effects similar to PPE, were treated with a meanwhile commercially available ointment. Results: At the beginning of the therapy, 46 patients suffered from a PPE of severity grade III, while in 22 patients a PPE of severity grade II was diagnosed. The application of the ointment resulted in a significant improvement of the clinical symptoms and the skin status in all these patients; their chemotherapies could be continued. Conclusion: The obtained results suggest that radical-forming processes play an essential role in a great number of chemotherapeutics which induce dermal side effects. The topical application of the antioxidant-containing ointment proved to be a good therapeutic option which needs further evaluation.

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Efficient Prevention Strategy against the Development of a Palmar-Plantar Erythrodysesthesia during Chemotherapy

Cited by 21 publications

References 19 publications

Influence of Mechanical Stress on Palmoplantar Erythrodysesthesia - a Case Report

Influence of Mechanical Stress on Palmoplantar Erythrodysesthesia - a Case Report

Strategies for Prevention and Treatment of Chemotherapy-Induced Hand-Foot- Skin-Reaction (HFSR)

Palmoplantar Erythrodysesthesia-Like Skin Symptoms in Patients under Various Chemotherapeutics: Preventive and Therapeutic Options

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