Periocular Chemotherapy in Palpebral Malignancies: A Review

Nabita Aulia, Halimah Pagarra, Suliati P Amir, Andi Pratiwi


Background: Palpebral malignancy is still a significant health problem and consists of sebaceous gland carcinoma (SGC), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Although total resection using the Moh micrograph method is standard therapy for these cases, perioral chemotherapy may be an alternative therapy in patients where surgery cannot be performed.

Content: Periocular chemotherapy in lid malignancy is recommended in cases that are inhibited or contraindicated for surgery, with obscure tumor margins, with markers of tumor invasion of vascular, lymphatic, nerve, or other orbital structures, signs of relapse after surgery, local pagetoid involvement, sizeable tumor size, and also presented an appearance of diffuse and multifocal tumor on histopathological examination. Choices of local chemotherapeutic agents based on the variety of palpebral malignancy, namely: (1) imiquimod for BCC; (2) mitomycin-C for SGC; (3) cisplatin, doxorubicin, bleomycin, peplomycin, methotrexate, and 5-fluorouracil for SCC; and (4) Imiquimod for MM. Topical chemotherapy is given to patients using an iodontotherapy method or ophthalmic cream.. More often than not, topical chemotherapy possessed a few side effects that are mild and tolerable and disappear on their own after treatment has finished.

Conclusion: Local/periocular chemotherapy for palpebral malignancy is an alternative adjuvant therapy that can be considered, especially in cases where surgery is not possible.


Key words: Malignancy, chemotherapy, palpebral, periocular

Full Text:



Balasubramanian A. Eyelid Malignancies- Always Quite Challenging. J Clin Diagn Res. Published online 2017. doi:10.7860/JCDR/2017/23695.9582

Kaliki S, Bothra N, Bejjanki KM, et al. Malignant Eyelid Tumors in India: A Study of 536 Asian Indian Patients. Ocul Oncol Pathol. 2019;5(3):210-219. doi:10.1159/000491549

Luxenberg MN, Guthrie TH. Chemotherapy of eyelid and peritorbital tumors. Trans Am Ophthalmol Soc. 1985;83:162-180.

Shi Y, Jia R, Fan X. Ocular basal cell carcinoma: a brief literature review of clinical diagnosis and treatment. OncoTargets Ther. 2017;10:2483-2489. doi:10.2147/OTT.S130371

Mehta M, Fay A. Squamous cell carcinoma of the eyelid and conjunctiva. Int Ophthalmol Clin. 2009;49(1):111-121. doi:10.1097/IIO.0b013e3181928fb9

Sanchez R, Ivan D, Esmaeli B. Eyelid and periorbital cutaneous malignant melanoma. Int Ophthalmol Clin. 2009;49(4):25-43. doi:10.1097/IIO.0b013e3181b7eea7

Pe’er J. Pathology of eyelid tumors. Indian J Ophthalmol. 2016;64(3):177. doi:10.4103/0301-4738.181752

Yin VT, Pfeiffer ML, Esmaeli B. Targeted Therapy for Orbital and Periocular Basal Cell Carcinoma and Squamous Cell Carcinoma. Ophthal Plast Reconstr Surg. 2013;29(2):10.1097/IOP.0b013e3182831bf3. doi:10.1097/IOP.0b013e3182831bf3

Macha MA, Batra SK, Ganti AK. Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma. Cancer Manag Res. 2013;5:197-203. doi:10.2147/CMAR.S45976

Yunoki T, Tabuchi Y, Hirano T, Miwa S, Imura J, Hayashi A. Gene networks in basal cell carcinoma of the eyelid, analyzed using gene expression profiling. Oncol Lett. 2018;16(5):6729-6734. doi:10.3892/ol.2018.9484

Shi Y, Jia R, Fan X. Ocular basal cell carcinoma: a brief literature review of clinical diagnosis and treatment. OncoTargets Ther. 2017;Volume 10:2483-2489. doi:10.2147/OTT.S130371

Al-Mujaini A, Wali U. Sebaceous gland carcinoma of the eyelid. Oman J Ophthalmol. 2010;3(3):117. doi:10.4103/0974-620X.71885

Kaliki S, Ayyar A, Dave TV, Ali MJ, Mishra DK, Naik MN. Sebaceous gland carcinoma of the eyelid: clinicopathological features and outcome in Asian Indians. Eye. 2015;29(7):958-963. doi:10.1038/eye.2015.79

Honavar S. Sebaceous gland carcinoma: Can we do better? Indian J Ophthalmol. 2018;66(9):1235. doi:10.4103/ijo.IJO_1370_18

Shields JA, Demirci H, Marr BP, Eagle RC, Shields CL. Sebaceous carcinoma of the eyelids. Ophthalmology. 2004;111(12):2151-2157. doi:10.1016/j.ophtha.2004.07.031

Bligh HF, Bartoszek A, Robson CN, et al. Activation of mitomycin C by NADPH:cytochrome P-450 reductase. Cancer Res. 1990;50(24):7789-7792.

Paz MM, Zhang X, Lu J, Holmgren A. A new mechanism of action for the anticancer drug mitomycin C: mechanism-based inhibition of thioredoxin reductase. Chem Res Toxicol. 2012;25(7):1502-1511. doi:10.1021/tx3002065

Shulstad R, Steven P. Squamous Cell Carcinoma. J Dermatol Nurses Assoc. 2010;2(1):12-16.

Robert M. Treatment of invasive periocular squamous cell carcinomas combining surgery and local chemotherapy. Prat Vét Equine. 2019;51(203):32-38.

Meel R, Dhiman R, Kashyap S, Agrawal S, Pushker N, Bakhshi S. Systemic neoadjuvant chemotherapy in non-resectable invasive squamous cell carcinoma of ocular surface. Eur J Ophthalmol. Published online April 30, 2021:11206721211014376. doi:10.1177/11206721211014376

Hagmann W, Jesnowski R, Faissner R, Guo C, Löhr JM. ATP-Binding Cassette C Transporters in Human Pancreatic Carcinoma Cell Lines. Pancreatology. 2009;9(1-2):136-144. doi:10.1159/000178884

Ceckova M, Vackova Z, Radilova H, Libra A, Buncek M, Staud F. Effect of ABCG2 on cytotoxicity of platinum drugs: Interference of EGFP. Toxicol In Vitro. 2008;22(8):1846-1852. doi:10.1016/j.tiv.2008.09.001

Martel A, Oberic A, Moulin A, Zografos L, Hamedani M. Eyelids metastases from uveal melanoma: clinical and histopathologic features of two cases and literature review. Eye. 2019;33(5):767-771. doi:10.1038/s41433-018-0317-7

Heistein JB, Acharya U, Mukkamalla SKR. Malignant Melanoma. In: StatPearls. StatPearls Publishing; 2023. Accessed August 31, 2023.

Hersh EM, O’Day SJ, Ribas A, et al. A phase 2 clinical trial of nab-paclitaxel in previously treated and chemotherapy-naive patients with metastatic melanoma. Cancer. 2010;116(1):155-163. doi:10.1002/cncr.24720

Liu Y, Sheikh MS. Melanoma: Molecular Pathogenesis and Therapeutic Management. Mol Cell Pharmacol. 2014;6(3):228.

McCubrey JA, Steelman LS, Abrams SL, et al. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzyme Regul. 2006;46:249-279. doi:10.1016/j.advenzreg.2006.01.004

Luke JJ, Schwartz GK. Chemotherapy in the management of advanced cutaneous malignant melanoma. Clin Dermatol. 2013;31(3):290-297. doi:10.1016/j.clindermatol.2012.08.016

Chan FM, O’Donnell BA, Whitehead K, Ryman W, Sullivan TJ. Treatment and Outcomes of Malignant Melanoma of the Eyelid. Ophthalmology. 2007;114(1):187-192. doi:10.1016/j.ophtha.2006.08.043

Balasubramanian A, Kannan NS. Eyelid Malignancies- Always Quite Challenging. J Clin Diagn Res JCDR. 2017;11(3):XR01-XR04. doi:10.7860/JCDR/2017/23695.9582.



  • There are currently no refbacks.

Jambura Medical and Health Science Journal (JMHSJ) has been indexed by:

Editorial Office

Faculty of Medicine, Universitas Negeri Gorontalo
Medical Faculty Building, 1st Floor
Jl. Jend. Sudirman No.6, Kota Gorontalo, Gorontalo, 96128, Indonesia.Whatsapp: +6285233215280 Email:


Creative Commons Licence
Jambura Medical and Health Science Journal (JMHSJ), is licensed under a Lisensi Creative Commons Atribusi 4.0 Internasional.