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Supportive Care in Cancer

, Volume 27, Issue 12, pp 4535–4542 | Cite as

Cutaneous toxicities of antineoplastic agents: data from a large cohort of Greek patients

  • Vasiliki NikolaouEmail author
  • D. Voudouri
  • G. Tsironis
  • A. Charpidou
  • G. Stamoulis
  • I. Triantafyllopoulou
  • I. Panoutsopoulou
  • E. Xidakis
  • A. Bamias
  • E. Samantas
  • G. Aravantinos
  • H. Gogas
  • D. Rigopoulos
  • K. Syrigos
  • A. Stratigos
Original Article
  • 127 Downloads

Abstract

Purpose

Cutaneous toxicities from novel anticancer treatments are an emerging problem in dermato-oncology. However, the prevalence of those toxicities and necessity of skin consultations are currently unknown. The purpose of our study was to perform an epidemiologic analysis of cutaneous toxicities that were referred to our cutaneous toxicity clinic in Athens, Greece.

Methods

All patients examined at the oncodermatology department over a 42-month period were included. Gender, age, type of cancer, type of antineoplastic treatment, and type of toxicity were recorded and analyzed.

Results

Four hundred fifty-nine patients (182 males, 277 females) with mean age (SD) 60.6 years (13.05) were included in the analysis. Six hundred seventy-two cutaneous toxicities were recorded. Chemotherapy-induced toxicities were the most commonly recorded incidents, with taxanes being the most commonly involved agent. Immune-related adverse events (IRAEs) have steadily increased over the past 3 years. Treatment modifications due to skin toxicities were more common in patients treated with targeted agents and immune checkpoint inhibitors than in those treated with chemotherapy. The toxicities that led to the most treatment modifications were acneiform eruptions and perionychias. The most common IRAEs recorded were psoriasis in 11 patients, followed by pruritus, macular rash, and lichenoid-type eruptions. In addition, 4 interesting cases of IRAEs are discussed.

Conclusion

Antineoplastic treatments can lead to a wide range of cutaneous toxicities. Our study underlines the need for a multidisciplinary approach in oncologic patients. The dermatologists’ role is crucial in effectively managing those reactions and preventing antineoplastic drug dose adjustments or discontinuation of treatment.

Keywords

Cutaneous toxicities Immune-related adverse effects Acneiform eruption Perionychia 

Notes

Compliance with ethical standards

Disclosure of potential conflicts of interest

Please find the attached disclosure forms. We have full control of all primary data and we agree to allow the journal to review the data if requested.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR (2015) Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 373:123–135.  https://doi.org/10.1056/NEJMoa1504627 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Weber JS, D’Angelo SP, Minor D et al (2015) Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 16:375–384.  https://doi.org/10.1016/S1470-2045(15)70076-8 CrossRefPubMedGoogle Scholar
  3. 3.
    Hu JC, Sadeghi P, Pinter-Brown LC, Yashar S, Chiu MW (2007) Cutaneous side effects of epidermal growth factor receptor inhibitors: clinical presentation, pathogenesis and management. J Am Acad Dermatol 56:317–326.  https://doi.org/10.1016/j.jaad.2006.09.005 CrossRefPubMedGoogle Scholar
  4. 4.
    Chu EY, Wanat KA, Miller CJ, Amaravadi RK, Fecher LA, Brose MS, McGettigan S, Giles LR, Schuchter LM, Seykora JT, Rosenbach M (2012) Diverse cutaneous side effects associated with BRAF inhibitor therapy: a clinicopathologic study. J Am Acad Dermatol 67:1265–1272.  https://doi.org/10.1016/j.jaad.2012.04.008 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD (2015) Toxicities of the anti-PD1 and anti-PDL1 immune checkpoint antibodies. Ann Oncol 26:2375–2391.  https://doi.org/10.1093/annonc/mdv383 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sibaud V, Leboeuf NR, Roche H et al (2016) Dermatological adverse events with taxane chemotherapy. Eur J Dermatol 26:427–443.  https://doi.org/10.1684/ejd.2016.2833 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Markman M (2003) Managing taxane toxicities. Support Care Cancer 11:144–147.  https://doi.org/10.1007/s00520-002-0405-9 CrossRefPubMedGoogle Scholar
  8. 8.
    Matsumoto K, Hino C, Fukada K et al (2009) Prospective study of ice gel pack as less expensive alternative for prevention of skin and nail toxicity in patients with breast cancer receiving docetaxel. Cancer Res 69: Abstract 1114. doi:  https://doi.org/10.1158/0008-5472.SABCS-09-1114
  9. 9.
    Nikolaou V, Syrigos K, Saif MW (2016) Incidence and implications of chemotherapy related hand-foot syndrome. Expert Opin Drug Saf 15:1625–1633.  https://doi.org/10.1080/14740338.2016.1238067 CrossRefPubMedGoogle Scholar
  10. 10.
    Anderson RT, Keating KN, Doll HA, Camacho F (2015) The hand-foot skin reaction and quality of life questionnaire: an assessment tool for oncology. Oncologist 20:831–838.  https://doi.org/10.1634/theoncologist.2014-0219 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Degen A, Alter M, Schenck F, Satzger I, Völker B, Kapp A, Gutzmer R (2010) The hand-foot-syndrome associated with medical tumor therapy classification and management. J Dtsch Dermatol Ges 8:652–661.  https://doi.org/10.1111/j.1610-0387.2010.07449.x CrossRefPubMedGoogle Scholar
  12. 12.
    Chu D, Lacouture ME, Fillos T, Wu S (2008) Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis. Acta Oncol 47:176–186.  https://doi.org/10.1080/02841860701765675 CrossRefPubMedGoogle Scholar
  13. 13.
    Belum VR, Benhuri B, Postow MA, Hellmann MD, Lesokhin AM, Segal NH, Motzer RJ, Wu S, Busam KJ, Wolchok JD, Lacouture ME (2016) Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur J Cancer 60:12–25.  https://doi.org/10.1016/j.ejca.2016.02.010 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Hwang SJE, Carlos G, Wakade D, Byth K, Kong BY, Chou S, Carlino MS, Kefford R, Fernandez-Penas P (2016) Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: a single-institution cohort. J Am Acad Dermatol 74:455–461.  https://doi.org/10.1016/j.jaad.2015.10.029 CrossRefPubMedGoogle Scholar
  15. 15.
    Kato Y, Otsuka A, Miyachi Y, Kabashima K (2016) Exacerbation of psoriasis vulgaris during nivolumab for oral mucosal melanoma. J Eur Acad Dermatol Venereol 30:e89–e91.  https://doi.org/10.1111/jdv.13336 CrossRefPubMedGoogle Scholar
  16. 16.
    Matsumura N, Ohtsuka M, Kikuchi N, Yamamoto T (2016) Exacerbation of psoriasis during nivolumab therapy for metastatic melanoma. Acta Derm Venereol 96:259–260.  https://doi.org/10.2340/00015555-2212 CrossRefPubMedGoogle Scholar
  17. 17.
    Bonigen J, Raynaud-Donzel C, Hureaux J, Kramkimel N, Blom A, Jeudy G, Breton AL, Hubiche T, Bedane C, Legoupil D, Pham-Ledard A, Charles J, Pérol M, Gérard E, Combemale P, Bonnet D, Sigal ML, Mahé E, the Groupe de Recherche sur le Psoriasis and the Groupe Cancérologie Cutanée of the Société Française de Dermatologie the GEM Resopso, Apsoderm and the Groupe Français de Pneumo-Cancérologie (2017) Anti-PD1-induced psoriasis: a study of 21 patients. J Eur Acad Dermatol Venereol 31:e254–e257.  https://doi.org/10.1111/jdv.14011 CrossRefPubMedGoogle Scholar
  18. 18.
    Voudouri D, Nikolaou V, Laschos K, Charpidou A, Soupos N, Triantafyllopoulou I, Panoutsopoulou I, Aravantinos G, Syrigos K, Stratigos A (2017) Anti-PD1/PDL1 induced psoriasis. Curr Probl Cancer 41:407–412.  https://doi.org/10.1016/j.currproblcancer.2017.10.003 CrossRefPubMedGoogle Scholar
  19. 19.
    Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A, KEYNOTE-006 investigators (2015) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532.  https://doi.org/10.1056/NEJMoa1503093 CrossRefPubMedGoogle Scholar
  20. 20.
    Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34.  https://doi.org/10.1056/NEJMoa1504030 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    McDermott DF, Sosman JA, Sznol M et al (2016) Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity and immune correlates from a phase Ia study. J Clin Oncol 34:833–842.  https://doi.org/10.1200/JCO.2015.63.7421 CrossRefPubMedGoogle Scholar
  22. 22.
    Hua C, Boussemart L, Mateus C, Routier E, Boutros C, Cazenave H, Viollet R, Thomas M, Roy S, Benannoune N, Tomasic G, Soria JC, Champiat S, Texier M, Lanoy E, Robert C (2016) Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatol 152:45–51.  https://doi.org/10.1001/jamadermatol.2015.2707 CrossRefPubMedGoogle Scholar
  23. 23.
    Uenami T, Hosono Y, Ishijima M, Kanazu M, Akazawa Y, Yano Y, Mori M, Yamaguchi T, Yokota S (2017) Vitiligo in a patient with lung adenocarcinoma treated with nivolumab: a case report. Lung Cancer 109:42–44.  https://doi.org/10.1016/j.lungcan.2017.04.019 CrossRefPubMedGoogle Scholar
  24. 24.
    Zarogoulidis P, Huang H, Tsiouda T, Sardeli C, Trakada G, Veletza L, Kallianos A, Kosmidis C, Rapti A, Papaemmanouil L, Hatzibougias D, Drougas D, Bai C, Hohenforst-Schmidt W (2017) Immunotherapy “shock” with vitiligo due to nivolumab administration as third line therapy in lung adenocarcinoma. Respir Med Case Rep 22:283–286.  https://doi.org/10.1016/j.rmcr.2017.10.006 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Larsabal M, Marti A, Jacquemin C, Rambert J, Thiolat D, Dousset L, Taieb A, Dutriaux C, Prey S, Boniface K, Seneschal J (2017) Vitiligo-like lesions occurring in patients receiving anti-programmed cell death-1 therapies are clinically and biologically distinct from vitiligo. J Am Acad Dermatol 76:863–870.  https://doi.org/10.1016/j.jaad.2016.10.044 CrossRefPubMedGoogle Scholar
  26. 26.
    Κhunger M, Calabrese C, Kontzias A, Velcheti V (2017) To treat or not to treat: role of immunotherapy in patients with concomitant diagnosis of advanced-stage non-small cell lung cancer and psoriasis. J Thorac Oncol 12:e147–e149.  https://doi.org/10.1016/j.jtho.2017.05.005 CrossRefGoogle Scholar
  27. 27.
    Βabey H, Quéré G, Descourt R et al (2018) Immune-checkpoint inhibitors to treat cancers in specific immunocompromised populations: a critical review. Expert Rev Anticancer Ther 18:981–989.  https://doi.org/10.1080/14737140.2018.1499468 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Vasiliki Nikolaou
    • 1
    Email author
  • D. Voudouri
    • 1
  • G. Tsironis
    • 2
  • A. Charpidou
    • 3
  • G. Stamoulis
    • 4
  • I. Triantafyllopoulou
    • 1
  • I. Panoutsopoulou
    • 1
  • E. Xidakis
    • 5
  • A. Bamias
    • 2
  • E. Samantas
    • 4
  • G. Aravantinos
    • 5
  • H. Gogas
    • 6
  • D. Rigopoulos
    • 1
  • K. Syrigos
    • 3
  • A. Stratigos
    • 1
  1. 1.Dermato-Oncology Department, Cutaneous Toxicities ClinicAndreas Sygros Hospital, National and Kapodistrian University of AthensAthensGreece
  2. 2.Department of Clinical Therapeutics, Alexandra General HospitalNational and Kapodistrian University of AthensAthensGreece
  3. 3.Third Department of Medicine, Oncology Unit, Sotiria General HospitalNational and Kapodistrian University of AthensAthensGreece
  4. 4.Third Department of Medical OncologyAgii Anargiri General Oncological Hospital of KifissiaAthensGreece
  5. 5.Second Department of Medical OncologyAgii Anargiri General Oncological Hospital of KifissiaAthensGreece
  6. 6.Oncology Section, First Department of Internal Medicine, General Hospital of Athens “Laiko”National and Kapodistrian University of AthensAthensGreece

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