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The Neurogenic Component of Cutaneous Toxicities Induced by Chemotherapy – New Solutions

Published Online: June 3rd 2011 European Oncology & Haematology, 2011;7(1):13-15 DOI: https://doi.org/10.17925/EOH.2011.07.01.13
Authors: Jean-François Chanez
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Abstract
Article
Article Information
Abstract:
Overview

Most chemotherapies cause cutaneous side effects. Docetaxel entered the therapeutic arsenal in the 1990s; while undeniably a sign of progress, it can also cause cutaneous side effects. Other chemotherapeutic drugs can induce secondary cutaneous effects, such as acneiform rash, hand–foot syndrome or mucositis. Hair loss, reversible or not, and nail disorders are also well-known deleterious effects encountered with several drugs used in oncology. Furthermore, the development of new targeted therapies is contributing to an increased frequency of these undesirable effects. New products that take into account the neurogenic phenomena implicated in the local inflammatory response to chemotherapy are required to offer new alternative care for various cutaneous and muco-cutaneous side effects.

Support: The publication of this article was funded by Evolife Laboratoires.

Keywords

Neurogenic inflammation, substance P, chemotherapy, mineral elements of Evaux thermal spring water

Article:

Docetaxel is effective against numerous tumours, mainly in metastatic breast cancers; however, it can lead to other conditions, in particular cutaneous reactions, such as onycholysis and hand–foot syndrome. The ungual toxicity of docetaxel is well-known and occurs in 40–50% of cases. The mechanism of this toxicity is of neurogenic origin. Local symptoms are due to incorrect information resulting from one or more lesions or anomalies in the nervous pathways that direct these painful nerve impulses to the sensory cerebral cortex. During large-scale release of neuromediators, particularly substance P, the inflammation becomes neurogenic. As substance P is one of the main agents implicated in inflammation of this type, any molecule preventing its release or blocking its post-synaptic action could be a potential inhibitor of this inflammation, which is deleterious to nails.

Ungual side effects following chemotherapy often involve progressive destruction of the nail that can lead to intense localised pain (onycholysis). The nail may crumble or even fall off, causing problems with walking when toenails are involved or gripping difficulties when fingernails are altered. Wasner et al.1 reported a case report about a patient suffering from a cancerous tumour in the right breast, who was rendered paralysed in the right arm following infiltration of the brachial plexus by this tumour. Treated with docetaxel, no ungual side effects appeared on the right (paralysed) side, while significant ungual side effects were observed on the patient’s left hand. The article underlines the neurogenic mechanism of side effects linked to chemotherapy. Substance P released under the effects of chemotherapy is described as pro-inflammatory and vasodilatory.

A new hydrophilic-film-forming solution containing lithium, Evonail®, acts by interfering with the signalling mechanisms determined following activation by the substance P receptors, as shown by Boisnic et al.2 In this in vitro study, a human sebocyte culture model was stimulated by substance P and corticotrophin-releasing hormone (to mimic stress conditions; see Figure 1A) and the mineral constituents of Evaux thermal spring water (including lithium) – both pure and diluted by 50% – had an an inhibitory effect on sebocyte proliferation (see Figure 1B). To clinically illustrate these preliminary results, some clinical case reports follow. Case Reports
Case Report 1

The first case report illustrates beneficial effects obtained with Evonail. A 48-year-old man presented with an acute ungual problem. He had been treated for a metastatic colorectal cancer with irinotecan (Campto® intravenous perfusion) at a rate of two treatments per month for three years. Ungual problems had appeared six months after beginning chemotherapy. These problems resulted in onycholysis of the ungual bed on all the nails of the fingers and toes, accompanied by intermittent ungual hyperpigmentation of undetermined aetiology (see Figures 2A and 2B). There was no prior dermatological history. Systematic cutaneous examination did not identify any particular alopoecia. The patient reported cutaneous hypersensitivity and recurrent presence of ulceration of the oral mucosa.

In order to reduce these ungual symptoms, Evonail Solution was applied morning and night on all nails and their edges using an application presented with deep heel fissures on both feet with pronounced hyperkeratosis and significant discomfort when applying pressure to the heel (see Figure 4A). He had been treated for cancer of the right maxillary sinus by the combination of carboplatine and cetuximab (Erbitux) for six months. In order to reduce the fissures, Evoskin Solution Spray was sprayed on the heels morning and night for the first two days, then Evoskin Gel Cream was applied as a follow-up at the same dosage. Evoskin Solution Spray and Gel Cream are formulated from mineral elements contained in Evaux thermal spring water (lithium, manganese, strontium). Two weeks after starting application of Evoskin, the fissures were closing and their haemorrhagic nature had disappeared, and the discomfort under pressure had eased (see Figure 4B). No intolerance to ungual Evoskin Solution Spray and Gel Cream was reported by the patient during the application period.

Cetuximab (Erbitux), an EGF receptor inhibitor, is a frequently used chemotherapeutic agent, especially in the treatment of ENT cancers expressing this receptor. The incapacitating fissured conditions induced by this molecule are often reported in the literature. The introduction of an effective product without side effects for topical use in a rapid timespan of several days for resolution of heel fissures observed during chemotherapy offers the patient a significant functional and aesthetic benefit by improving his or her quality of life and contributing to better adherence to the chemotherapy regimen.

Case Report 4
This final case report considers the mucositis scoring before and after applying EVOMUCY® Spray during ten days in four patients suffering from squamous cell carcinoma (SCC) or adenocarcinoma and treated by Taxotere® + 5-FU + cisplatin association. Oral Mucositis Assessment Scale (OMAS), World Health Organization (WHO) and National Cancer Institute Common Toxicity Criteria (NCI-CTC) score ranges were maintained on baseline value (WHO score range) or slightly increased (OMAS and NCI-CTC range) in three patients. Impact on pain and diet was also improved during EVOMUCY Spray use. Completion of this study is in progress.3

Conclusion
By underlining the involvement of neuromediators in cutaneous problems, particularly following chemotherapy, Evolife Laboratories offers complete, specific and innovative solutions for cutaneous and muco-cutaneous side effects induced by chemotherapy.

Article Information:
Disclosure

Jean-François Chanez is an employee of Evolife Laboratoires.

Correspondence

Jean-François Chanez, Service Recherche et Développement, Evolife Laboratoires, 67 Avenue de la République, 23110 Evaux les Bains, France. E: jfchanez@orange.fr

Received

2010-01-11T00:00:00

References

  1. Wasner G, Hilpert F, Schattschneider J, et al., Docetaxel-induced nail changes – a neurogenic mechanism: a case report, J Neur Oncol, 2002;58:167–74.
  2. Boisnic S, Branchet MC, Chanez JF, Evaluation of the inhibition of human sébocytes proliferation stimulated by substance P and corticotropinreleasing hormone by mineral constituents in Evaux thermal spring water, Nouv Dermatol, 2004;23:569–75.
  3. Lalla RV, Choquette LE, Chanez JF, Sharan S, An open-label study of EVOMUCY® Spray for chemotherapyinduced oral mucositis, Poster presented at the International Symposium Supportive Care in Cancer MASCC/ISOO, Vancouver, Canada, 24–26 June 2010.

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