Effets indésirables cutanés et retentissement sur la qualité de vie des inhibiteurs de mTOR au cours du traitement du cancer du rein

doi:10.1016/j.annder.2013.02.023

Annales de Dermatologie et de Vénéréologie

Volume 140, Issue 5, May 2013, Pages 353-362

https://doi.org/10.1016/j.annder.2013.02.023 Get rights and content

Résumé

Introduction

Les inhibiteurs de mammalian target of rapamycine (mTOR) sont des thérapies ciblées de plus en plus utilisées en cancérologie. Leurs effets indésirables cutanés sont souvent décrits de façon imprécise. L’objectif de cette étude était de décrire ces effets indésirables et d’en évaluer le retentissement sur la qualité de vie des patients.

Patients et méthode

Pendant 18 mois, 18 patients traités par inhibiteur de mTOR pour un cancer du rein ont eu un examen dermatologique lors de chaque consultation de suivi oncologique. Une évaluation de la qualité de vie par le questionnaire Skindex 30 était réalisée dès qu’un effet indésirable cutané était présent.

Résultats

Soixante-dix sept consultations de dermatologie ont eu lieu ; 15 des 18 patients inclus ont présenté des effets indésirables cutanés. Il s’agissait d’aphtes (61,1 %), de xérose (55,5 %), d’onycholyse distale (50 %), d’éruptions acnéiformes (38,8 %), de périonyxis (22,2 %) et de prurit (22,2 %). Le retentissement sur la qualité de vie était particulièrement marqué pour les aphtes et le périonyxis ; il était plus important dans le domaine physique (19 %), suivi des domaines émotionnel (9 %) et fonctionnel (6 %).

Conclusion

Les effets indésirables cutanés des inhibiteurs de mTOR sont fréquents et leur retentissement sur la qualité de vie particulièrement marqué pour le domaine physique. Une prise en charge précoce de ces effets indésirables par un dermatologue serait souhaitable pour améliorer la qualité de vie des patients.

Summary

Background

Mammalian target of rapamycine (mTOR) inhibitors are being increasingly prescribed as antitumoural drugs, and associated adverse cutaneous effects are frequent but poorly described. The aim of this study was to describe such adverse effects and to assess the quality of life of patients experiencing them.

Patients and methods

Over a period of 18 months, 18 patients treated with mTOR inhibitors for renal carcinoma were included and 77 dermatological examinations performed. Wherever a cutaneous adverse event was present, quality of life was evaluated using the Skindex 30 questionnaire.

Results

Fifteen of the 18 patients included presented adverse cutaneous events, consisting of buccal ulcers (61.1%), xerosis (55.5%), distal onycholysis (50%), acneiform eruption (38.8%), paronychia (22.2%) and pruritus (22.2%). Buccal ulcerations and perionyxis had an especially marked impact on quality of life, which was greatest in terms of physical score (19%), followed by emotional (9%) and functional (6%) scores.

Conclusion

Cutaneous adverse effects of mTOR inhibitors are frequent and have a considerable impact on quality of life, particularly as regards physical scores. Dermatological examination appears useful to allow early management of cutaneous adverse effects and improve the quality of life of these patients.

Section snippets

Patients et méthode

Les patients suivis dans le centre régional de lutte contre le cancer et traités par inhibiteurs de mTOR ont été suivis en dermatologie de manière prospective de mars 2011 à juin 2012. Les patients dont le traitement par inhibiteur de mTOR avait été débuté avant mars 2011 étaient également inclus dans l’étude. Les données suivantes ont été recueillies : âge, sexe, date de diagnostic de la pathologie cancéreuse, traitements antérieurs, date de début du traitement par inhibiteur de mTOR. Si

Résultats

Dix-huit patients (12 hommes, six femmes) ont été suivis de façon prospective avec 77 consultations dermatologiques, soit en moyenne 4,3 consultations par patient (un à huit). La moyenne d’âge était de 65,2 ans (54 à 80 ans). L’inhibiteur de mTOR utilisé était dans 15 cas l’évérolimus et dans trois cas le temsirolimus. Les données de la littérature ne permettant pas de distinguer les effets indésirables dus à ces deux thérapeutiques [5], nous ne les avons pas analysés séparément. La durée moyenne

Discussion

Cette étude souligne la fréquence des effets indésirables cutanéo-muqueux chez les patients traités par inhibiteurs de mTOR, puisqu’ils furent observés chez 15 des 18 malades suivis. Ces effets secondaires surviennent principalement lors des six premiers mois de traitement et peuvent persister sous forme de lésions permanentes (onycholyse distale) ou évoluer par poussées (lésions aphtoïdes buccales). Les lésions aphtoïdes buccales sont les plus précoces à apparaître. Ces effets indésirables

Conclusion

Nous rapportons la première série prospective étudiant les effets secondaires cutanés observés chez des patients traités par inhibiteurs de mTOR pour un cancer du rein. Ces molécules ont une toxicité cutanée fréquente et un retentissement sur la qualité de vie des patients. Cette toxicité est essentiellement marquée par l’apparition d’aphtes, d’une onycholyse, d’une xérose et d’éruptions acnéiformes. Elle est rarement responsable d’une interruption du traitement mais peut être améliorée par des

Déclaration d’intérêts

Les auteurs déclarent ne pas avoir de conflits d’intérêts en relation avec cet article.

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Results: We identified (+)-cyanidan-3-ol (CD-3) as a selective compound for inhibiting the growth of SCSC cell lines. CD-3 inhibited tumor growth and burden without apparent toxicity and prolonged the survival of tumor-bearing mice. CD-3 inhibitory effects on SCSC growth are mediated via cell cycle arrest and caspase-dependent apoptosis induction. Mechanistic studies showed that CD-3 activates PP2A via inhibiting CIP2A and produces tumor growth inhibitory effects via promoting dephosphorylation of oncogenic AKT/mTOR signaling proteins in SCSC cells and xenograft tumors in a PP2A dependent manner. Furthermore, the combination of CD-3 and mTOR inhibitors (mTORi) synergistically reduced oncogenic phenotypes.
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cross-sectional studies which evaluated the quality of life of patients having developed secondary cutaneous effects. This was most often done at the moment of the consultation in oncology or in dermatology and with an average lapse of time of 4–6 weeks after the beginning of the targeted treatment (Andreis et al., 2010; Boers-Doets et al., 2013; Coleman et al., 2011; Huggins et al., 2008; Joshi et al., 2010; Nardone et al., 2012; Osio et al., 2009; Romito et al., 2010; Rosen et al., 2013; Voilliot-Trotota et al., 2013; Wagner and Lacouture, 2007; Wagner et al., 2013; Witherspoon et al., 2008); prospective studies, which evaluated the quality of life of patients treated with targeted therapy at intervals over several months, using the first evaluation at the beginning of the treatment as a reference point (Au et al., 2005; Charles et al., 2013; Molinari et al., 2005; Peeters et al., 2009; Thaler et al., 2012);
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Dermatologic adverse events globally have a low to moderate impact on quality of life, mainly in the physical and emotional domains. Reasons for inter-individual variations in adjustment and long-term impact are still not well known. Making quality of life assessments systematic, making early referrals of patients to dermatology consultations and giving more attention to individual experience were identified as measures that could help prevent deterioration in quality of life.
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Mémoire originalEffets indésirables cutanés et retentissement sur la qualité de vie des inhibiteurs de mTOR au cours du traitement du cancer du reinAdverse cutaneous effects and quality of life in patients treated with mTOR inhibitors for renal carcinoma

Résumé

Introduction

Patients et méthode

Résultats

Conclusion

Summary

Background

Patients and methods

Results

Conclusion

Section snippets

Patients et méthode

Résultats

Discussion

Conclusion

Déclaration d’intérêts

Lancet

J Am Acad Dermatol

Ann Oncol

Eur J Cancer

Ann Chir Plast Esthet

J Invest Dermatol

Eur Urol

Version française du Skindex (Skindex-France). Adaptation et évaluation des propriétés psychométriques

Ann Dermatol Venereol

A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group

Support Care Cancer

Manifestations dermatologiques des inhibiteurs de mTOR

Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors

Cancer

Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma

N Engl J Med

Mémoire original
Effets indésirables cutanés et retentissement sur la qualité de vie des inhibiteurs de mTOR au cours du traitement du cancer du reinAdverse cutaneous effects and quality of life in patients treated with mTOR inhibitors for renal carcinoma