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Augenheilkunde up2date 2024; 14(01): 13-30
DOI: 10.1055/a-2051-0784
Tränenwege, Augenlider, Orbita

Medikamentöse Therapie von malignen Lidtumoren

Medicamentous Therapy of Malignant Eyelid Tumors
Daniel Walsch
,
Olga Furashova
,
Steffen Emmert
,
Vinodh Kakkassery
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Im Kontakt mit ophthalmologischen Patient*innen sind Fragestellungen hinsichtlich tumoröser Prozesse der Augenlider alltäglich. Meist handelt es sich um gutartige Läsionen, deren Therapieoptionen übersichtlich und deren Prognose gut ist. Dennoch ist hierbei stets höchste Sorgfalt geboten, denn maligne Läsionen lassen sich teilweise schwer von benignen unterscheiden. Ein Übersehen kann fatale Folgen für die Patient*innen bedeuten.

Abstract

Introduction Although surgical therapy is often the first-line treatment for malignant eyelid tumors, pharmacological treatment approaches can also be included and pursued in the treatment plan.

Methods Narrative review with a selective literature search on PubMed and Google Scholar.

Results Various pharmacological therapeutic principles are currently available. One option is the local application of agents within the tumor area. This can be achieved through cytostatically active drugs such as 5-fluorouracil for superficial basal cell carcinomas and precursors of squamous cell carcinomas, or through mitomycin C in specific cases of sebaceous gland carcinoma. Another form of pharmacological local therapy is local immunomodulation using Imiquimod for superficial basal cell carcinomas, actinic keratosis, and Bowenʼs disease. Furthermore, there are systemic pharmacological therapies like chemotherapies, for example in sebaceous cell carcinoma, or systemic immunomodulation using checkpoint inhibitors for example in basal cell carcinoma, squamous cell carcinoma, Merkel cell carcinoma, and melanoma. Additionally, targeted therapies offer yet another treatment modality that exploits the molecular biological characteristics of various tumor entities. Examples of this include Hedgehog inhibitors for basal cell carcinomas, EGFR inhibitors for squamous cell carcinomas, or BRAF inhibitors for melanomas. This review addresses these treatment options for malignant tumors of the eyelid and systematically organizes them for the reader.

Conclusion Even though the data on these eye tumors is still limited, the reported case studies using systemic therapies for malignant eyelid tumors demonstrate the potential of this treatment modality. However, the need for further research is high especially concerning the combination of different therapy principles for increasing the effectiveness of eyelid tumor therapy.

Kernaussagen

  • Der Vormarsch molekularbiologischer Methoden in der Charakterisierung von Malignomen ist auch bezüglich Lidtumoren präsent.

  • Dies ermöglicht die Identifizierung von Tumoreigenschaften, welche pharmakologische Angriffspunkte liefern.

  • Hierdurch entsteht die Möglichkeit neben etablierten Methoden wie Chirurgie oder Radiotherapie gezielt mit einer Systemtherapie gegen Lidmalignome vorzugehen.

  • Am prominenten Beispiel des Basalzellkarzinoms zeigt sich jedoch auch, dass die Nutzung einzelner molekularbiologischer Ziele nicht dauerhaft ausreicht.

  • Entwickeln sich Resistenzen der Malignomzellen gegen eine Substanzklasse, bedarf es neuer pharmakologischer Angriffspunkte.

  • Hierdurch ergibt sich ein weiterer Forschungsbedarf, um zukünftig ein längerfristiges Ansprechen auf Systemtherapien für die Patient*innen gewährleisten zu können.

Schlüsselwörter

Hautkrebs - Augenlid - Systemtherapie - topische Therapie

Key words

Skin cancer - eyelid - systemic therapy - topical therapy


Publication History

Article published online:
27 February 2024

© 2024. Thieme. All rights reserved.

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  • Literatur

  • 1 Adamski WZ, Maciejewski J, Adamska K. et al. The prevalence of various eyelid skin lesions in a single-centre observation study. Adv Dermatol Alergol 2021; 38: 804-807
    CrossrefPubMedSearch in Google Scholar
  • 2 Deprez M, Uffer S. Clinicopathological features of eyelid skin tumors. a retrospective study of 5504 cases and review of literature. Am J Dermatopathology 2009; 31: 256-262
    CrossrefPubMedSearch in Google Scholar
  • 3 Kaspi M, Cinotti E, Perrot J-L. et al. Eyelid and Conjunctival Tumors. Stuttgart: Springer Nature Switzerland AG; 2020
    CrossrefSearch in Google Scholar
  • 4 Baş Z, Sharpe J, Yaghy A. et al. Prevalence of and associated factors for eyelid cancer in the American Academy of Ophthalmology Intelligent Research in Sight Registry. Ophthalmology Science 2023; 3: 100227
    CrossrefPubMedSearch in Google Scholar
  • 5 Leung C, Johnson D, Pang R. et al. Identifying predictive morphologic features of malignancy in eyelid lesions: The LUI triage key. Canadian Family Physician 2015; 61: e43-e49
    PubMedSearch in Google Scholar
  • 6 Berking C, Steeb T, Leiter U. et al. S3-Leitlinie „Aktinische Keratose und Plattenepithelkarzinom der Haut“. Forum Fam Plan West Hemisph 2020; 35: 93-99
    CrossrefSearch in Google Scholar
  • 7 Eigentler TK, Hoge J, Schadendorf D. et al. S3-Leitlinie zur Diagnostik, Therapie und Nachsorge des Melanoms. J Dtsch Dermatol Ges 2020; 18 (10)
    CrossrefPubMedSearch in Google Scholar
  • 8 Lang BM, Balermpas P, Bauer A. et al. S2k-Leitlinie Basalzellkarzinom der Haut. 2017. Im Internet (Stand 03.11.2023): https://register.awmf.org/assets/guidelines/032-021l_S2k_Basalzellkarzinom-der-Haut_2018-09_01.pdf
  • 9 Becker JC, Eigentler T, Frerich B. et al. S2k-Leitlinie-Merkelzellkarzinom. Im Internet (Stand 03.11.2023): https://register.awmf.org/assets/guidelines/032-023l_S2k_Merkelzellkarzinom_2018-12-verlaengert_01.pdf
  • 10 Owen JL, Kibbi N, Worley B. et al. Sebaceous carcinoma: evidence-based clinical practice guidelines. Lancet Oncol 2019; 20: e699-e714
    CrossrefPubMedSearch in Google Scholar
  • 11 Svendsen FH, Rasmussen PK, Coupland SE. et al. Lymphoma of the eyelid – an international multicenter retrospective study. Am J Ophthalmol 2017; 177: 58-68
    CrossrefPubMedSearch in Google Scholar
  • 12 Takagawa Y, Tamaki W, Suzuki S. et al. Radiotherapy for localized sebaceous carcinoma of the eyelid: A retrospective analysis of 83 patients. J Radiat Res 2019; 60: 622-629
    CrossrefPubMedSearch in Google Scholar
  • 13 Shi Y, Jia R, Fan X. Ocular basal cell carcinoma: A brief literature review of clinical diagnosis and treatment. Onco Targets Ther 2017; 10: 2483-2489
    CrossrefPubMedSearch in Google Scholar
  • 14 Yin V, Pfeiffer M, Esmaeli B. Targeted therapy for orbital and periocular basal cell carcinoma and squamous cell carcinoma. Ophthalmic Plast Reconstr Surg 2013; 29: 87-92
    CrossrefPubMedSearch in Google Scholar
  • 15 Curragh DS, Huilgol SC, Selva D. Neoadjuvant vismodegib in the management of locally advanced periocular basal cell carcinoma. Eye (Basingstoke) 2021; 35: 2740-2745
    CrossrefPubMedSearch in Google Scholar
  • 16 Pricl S, Cortelazzi B, Dal Col V. et al. Smoothened (SMO) receptor mutations dictate resistance tovismodegib in basal cell carcinoma. Mol Oncol 2015; 9: 389-397
    CrossrefPubMedSearch in Google Scholar
  • 17 Shi K, Wang G, Pei J. et al. Emerging strategies to overcome resistance to third-generation EGFR inhibitors. J Hematol Oncol 2022; 15: 94
    CrossrefPubMedSearch in Google Scholar
  • 18 Hartman RI, Lin JY. Cutaneous melanoma–A review in detection, staging, and management. Hematol Oncol Clin North Am 2019; 33: 25-38
    CrossrefPubMedSearch in Google Scholar
  • 19 Martel A, Lassalle S, Picard-Gauci A. et al. New targeted therapies and immunotherapies for locally advanced periocular malignant tumours: Towards a new ‘eye-sparing’ paradigm?. Cancers (Basel) 2021; 13: 2822
    CrossrefPubMedSearch in Google Scholar
  • 20 Welsh SJ, Corrie PG. Management of BRAF and MEK inhibitor toxicities in patients with metastatic melanoma. Ther Adv Med Oncol 2015; 7: 122-136
    CrossrefPubMedSearch in Google Scholar
  • 21 The 2018 Nobel Prize in Physiology or Medicine – Press release – NobelPrize.org. Im Internet (Stand: 06.06.2023): https://www.nobelprize.org/prizes/medicine/2018/press-release/
  • 22 Habib LA, Wolkow N, Freitag SK. et al. Advances in immunotherapy and periocular malignancy. Semin Ophthalmol 2019; 34: 327-333
    CrossrefPubMedSearch in Google Scholar
  • 23 Stratigos AJ, Sekulic A, Peris K. et al. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Lancet Oncol 2021; 22: 848-857
    CrossrefPubMedSearch in Google Scholar
  • 24 Ascierto PA, Schadendorf D. Update in the treatment of non-melanoma skin cancers: the use of PD-1 inhibitors in basal cell carcinoma and cutaneous squamous-cell carcinoma. J Immunother Cancer 2022; 10 (12)
    CrossrefPubMedSearch in Google Scholar
  • 25 Véron M, Chevret S, Grob JJ. et al. Safety and efficacy of nivolumab, an anti-PD1 immunotherapy, in patients with advanced basal cell carcinoma, after failure or intolerance to sonic Hedgehog inhibitors: UNICANCER AcSé NIVOLUMAB trial. Eur J Cancer 2022; 177: 103-111
    CrossrefPubMedSearch in Google Scholar
  • 26 Chang ALS, Tran DC, Cannon JGD. et al. Pembrolizumab for advanced basal cell carcinoma: An investigator-initiated, proof-of-concept study. J Am Acad Dermatol 2019; 80: 564-566
    CrossrefPubMedSearch in Google Scholar
  • 27 Migden MR, Rischin D, Schmults CD. et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med 2018; 379: 341-351
    CrossrefPubMedSearch in Google Scholar
  • 28 Migden MR, Khushalani NI, Chang ALS. et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol 2020; 21: 294-305
    CrossrefPubMedSearch in Google Scholar
  • 29 Ferrarotto R, Amit M, Nagarajan P. et al. Pilot phase II trial of neoadjuvant immunotherapy in locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck. Clinical Cancer Research 2021; 27: 4557-4565
    CrossrefPubMedSearch in Google Scholar
  • 30 Munhoz RR, Nader-Marta G, de Camargo VP. et al. A phase 2 study of first-line nivolumab in patients with locally advanced or metastatic cutaneous squamous-cell carcinoma. Cancer 2022; 128: 4223-4231
    CrossrefPubMedSearch in Google Scholar
  • 31 Grob JJ, Gonzalez R, Basset-Seguin N. et al. Pembrolizumab monotherapy for recurrent or metastatic cutaneous squamous cell carcinoma: A single-arm phase II trial (KEYNOTE-629). J Clin Oncol 2020; 38: 2916-2925
    CrossrefPubMedSearch in Google Scholar
  • 32 Conger JR, Grob SR, Tao J. Massive periocular squamous cell carcinoma with response to pembrolizumab (Keytruda). Ophthalmic Plast Reconstr Surg 2019; 35: e127
    CrossrefPubMedSearch in Google Scholar
  • 33 Garcia GA, Kossler AL. Avelumab as an emerging therapy for eyelid and periocular Merkel cell carcinoma. Int Ophthalmol Clin 2020; 60: 91-102
    CrossrefPubMedSearch in Google Scholar
  • 34 Wolkow N, Jakobiec FA, Afrogheh AH. et al. High expression of programmed death ligand 1 and programmed death ligand 2 in ophthalmic sebaceous carcinoma: The case for a clinical trial of checkpoint inhibitors. Am J Ophthalmol 2020; 220: 128-139
    CrossrefPubMedSearch in Google Scholar
  • 35 Harrington KJ, Ferris RL, Gillison M. et al. Efficacy and safety of nivolumab plus ipilimumab vs. nivolumab alone for treatment of recurrent or metastatic squamous cell carcinoma of the head and Neck. JAMA Oncol 2023; 9: 779-789
    CrossrefPubMedSearch in Google Scholar
  • 36 Shoji MK, Rong AJ. Ipilimumab and nivolumab for treatment of eyelid spindle cell melanoma. Am J Ophthalmol 2023; 250: e1-e2
    CrossrefPubMedSearch in Google Scholar
  • 37 Tawbi HA, Schadendorf D, Lipson EJ. et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N Engl J Med 2022; 386: 24-34
    CrossrefPubMedSearch in Google Scholar
  • 38 Jenkins RW, Barbie DA, Flaherty KT. Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer 2018; 118: 9-16
    CrossrefPubMedSearch in Google Scholar
  • 39 Kaliki S, Ayyar A, Nair AG. et al. Neoadjuvant systemic chemotherapy in the management of extensive eyelid sebaceous gland carcinoma: A study of 10 cases. Ophthalmic Plast Reconstr Surg 2016; 32: 35-39
    CrossrefPubMedSearch in Google Scholar
  • 40 Verma S, Kumar N, Meel R. et al. Neoadjuvant systemic chemotherapy in sebaceous gland carcinoma of the eyelid: A retrospective study. Ocul Oncol Pathol 2021; 7: 251-256
    CrossrefPubMedSearch in Google Scholar
  • 41 Toto V, Colapietra A, Alessandri-Bonetti M. et al. Upper eyelid merkel cell carcinoma treated with neoadjuvant chemotherapy and surgical excision. Arch Craniofac Surg 2019; 20: 121-125
    CrossrefPubMedSearch in Google Scholar
  • 42 Luxenberg MN, Guthrie TH. Chemotherapy of eyelid and peritorbital tumors. Trans Am Ophthalmol Soc 1985; 83: 162
    PubMedSearch in Google Scholar
  • 43 Jia DD, Niu Y, Zhu H. et al. Prior Therapy with pegylated-interferon Alfa-2b improves the efficacy of adjuvant pembrolizumab in resectable advanced melanoma. Front Oncol 2021; 11
    CrossrefPubMedSearch in Google Scholar
  • 44 Lippman SM, Parkinson DR, Itri LM. et al. 13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst 1992; 84: 235-241
    CrossrefPubMedSearch in Google Scholar
  • 45 Qureshi YA, Karp CL, Dubovy SR. Intralesional interferon alpha-2b therapy for adnexal Kaposi sarcoma. Cornea 2009; 28: 941-943
    CrossrefPubMedSearch in Google Scholar
  • 46 Girbardt C, Mößner A, Wiedemann P. et al. Therapiealternativen zur chirurgischen Versorgung maligner Lidtumoren und deren Vorläuferstufen. Der Ophthalmologe 2020; 117: 478-483
    CrossrefPubMedSearch in Google Scholar
  • 47 Russell HC, Chadha V, Lockington D. et al. Topical mitomycin C chemotherapy in the management of ocular surface neoplasia: A 10-year review of treatment outcomes and complications. Br J Ophthalmol 2010; 94: 1316-1321
    CrossrefPubMedSearch in Google Scholar
  • 48 Kwon MJ, Shin HS, Nam ES. et al. Comparison of HER2 gene amplification and KRAS alteration in eyelid sebaceous carcinomas with that in other eyelid tumors. Pathol Res Pract 2015; 211: 349-355
    CrossrefPubMedSearch in Google Scholar
  • 49 Temblador A, Topalis D, Andrei G. et al. Synergistic targeting of the PI3K/mTOR and MAPK/ERK pathways in Merkel cell carcinoma. Tumour Virus Res 2022; 14: 200244
    CrossrefPubMedSearch in Google Scholar
  • 50 Tetzlaff MT, Singh RR, Seviour EG. et al. Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma. J Pathol 2016; 240: 84-95
    CrossrefPubMedSearch in Google Scholar
  • 51 Warnecke KK, Sieg P. Das Talgdrüsenkarzinom der Augenlider – Fallbeschreibung und Literaturübersicht. Klin Monbl Augenheilkd 2006; 223: 771-774
    Thieme ConnectPubMedSearch in Google Scholar