ABSTRACT Palpebral basal carcinoma represents 90% of ocular malignant tumors with high morbidity. Its incidence has a different behavior in different parts of the world and generally increases with age. Positive diagnosis is made by histological evaluation of the specimen by excisional biopsy. The ideal treatment is surgical, although other treatment options are available. Non-surgical treatment is aimed at eliminating the tumor, as well as avoiding the complications or functional and esthetic sequelae of surgery. Numerous options are recognized within the non-surgical therapeutic modality; imiquimod, 5-fluorouracil, Hedgehog pathway inhibitors and interferons. Several studies have demonstrated the usefulness of interferons in monotherapy or as combination therapy in patients not amenable to surgery. For this reason, it was decided to review the current scientific literature on the efficacy and safety of HeberFERON® in the treatment of palpebral basal cell carcinoma. An updated search was carried out taking into account the descriptors corresponding to the key words related to the subject under investigation, in the bibliographic databases Medline (PubMed search engine), SciELO, Ebsco, Clinical Key and Google Scholar. Thirty-five articles were retrieved whose content corresponded to the subject of the study.

RESUMEN El carcinoma basal palpebral representa un 90 % de los tumores malignos oculares con una alta morbilidad. Su incidencia tiene un comportamiento diferente en las distintas partes del mundo y, por lo general, aumenta con la edad. El diagnóstico positivo se realiza por la evaluación histológica de la muestra mediante biopsia escisional. El tratamiento ideal es el quirúrgico, aunque existen otras opciones de tratamiento. El no quirúrgico tiene como objetivo la eliminación del tumor, así como evitar las complicaciones o las secuelas funcionales y estéticas por la cirugía. Se reconocen numerosas opciones dentro de la modalidad terapéutica no quirúrgica; imiquimod, 5-fluorouracilo, inhibidores de la vía de Hedgehog y los interferones. Diversos estudios han demostrado la utilidad de los interferones en monoterapia o como terapia combinada, en pacientes no susceptibles de actuaciones quirúrgicas. Por esta razón, se decidió revisar la literatura científica actual sobre la eficacia y seguridad del HeberFERON® en el tratamiento del carcinoma basal palpebral. Se realizó una búsqueda actualizada teniendo en cuenta los descriptores correspondientes a las palabras clave relacionadas con la temática a investigar, en las bases de datos bibliográficas Medline (buscador PubMed), SciELO, Ebsco, Clinical Key y en Google Académico. Se recuperaron 35 artículos que su contenido respondía al tema de estudio.

ABSTRACT Objective: To determine the clinical response in patients with basal palpebral carcinoma treated with HeberFERON(. Methods: A descriptive study was carried out in patients with eyelid cell basal carcinoma tried with HeberFERON in the Cuban Institute of Ophthalmology "Ramón Pando Ferrer" from January 2013 to January 2015. The sample consisted of 10 patients who fulfilled the inclusion criteria. The study variables were: age, sex, skin color, clinical form, tumor diameter, histological subtype of the tumor, as well as the clinical response after treatment of the cases studied. In all the variables, absolute and relative frequencies were calculated. Results: Male gender and white-skinned subjects predominated. The clinical form ulcerative nodule, poorly differentiated histological tumor subtype, and objective clinical response were present in the patients studied. Conclusions: In most of the patients a good clinical answer was achieved to the treatment with HeberFERON, which becomes a new non surgical alternative.

RESUMEN Objetivo: Determinar la respuesta clínica en pacientes con carcinoma basal palpebral tratados con HeberFERON(. Métodos: Se realizó un estudio descriptivo en pacientes con carcinoma basal palpebral, a quienes se les aplicó HeberFERON( perilesional en el Instituto Cubano de Oftalmología “Ramón Pando Ferer”, de enero del año 2013 a enero de 2015. La muestra quedó constituida por 10 pacientes que cumplieron con los criterios de inclusión. Las variables del estudio fueron: edad, sexo, color de la piel, forma clínica, diámetro tumoral, subtipo histológico del tumor, así como la respuesta clínica después del tratamiento de los casos estudiados. Para todas las variables del estudio fueron calculadas las frecuencias absolutas y relativas. Resultados: Predominaron el género masculino y los sujetos de piel blanca. En los pacientes estudiados se presentaron la forma clínica nódulo ulcerativo, el subtipo histológico tumoral poco diferenciado y la respuesta clínica objetiva. Conclusiones: En la mayoría de los pacientes se logró una buena respuesta clínica al tratamiento con HeberFERON(, por lo que este tratamiento se convierte una nueva alternativa no quirúrgica.

ABSTRACT Objective: Evaluate the safety of HeberFERON in the treatment of basal cell eyelid carcinoma. Methods: A descriptive study was conducted of patients with basal cell eyelid carcinoma undergoing perilesional HeberFERON therapy from January 2013 to January 2018. The sample was composed of 20 patients meeting the inclusion criteria. The protocol dose was 3.5 x 106 UI perilesional twice a week for five consecutive weeks. The variables analyzed were age, sex, skin color and tumor location, as well as adverse event type and degree. Absolute and relative frequencies were estimated for all the study variables. Results: The prevailing age group in the study basal cell eyelid carcinoma population was 60-79 years (80%). The most common lesion site was the lower eyelid (60%). Eyelid erythema and injection site pain were the most frequent ocular adverse events (95.0% and 70.0%, respectively), presenting in 95% of the study subjects. Systemic adverse events (fever, arthralgia and headache) prevailed in 100% of the cases studied, among whom the degree of severity was mild. Conclusions: HeberFERON is a good non-surgical alternative for basal cell eyelid carcinoma. It is safe and well tolerated.

RESUMEN Objetivo: Evaluar la seguridad del HeberFERON( en el tratamiento del carcinoma basal palpebral. Métodos: Se realizó un estudio descriptivo en pacientes con carcinoma basal palpebral, a quienes se les aplicó HeberFERON( perilesional, de enero del año 2013 a enero de 2018. La muestra quedó constituida por 20 pacientes que cumplieron los criterios de inclusión. La dosis protocolizada fue de 3,5 x 106 UI, perilesional, dos veces a la semana por 5 semanas consecutivas. Las variables del estudio fueron: edad, sexo, color de la piel, localización del tumor, así como tipo y grado de evento adverso. Para todas las variables del estudio fueron calculadas las frecuencias absolutas y relativas. Resultados: La población estudiada con carcinoma basal palpebral mostró mayor frecuencia entre los 60 y 79 años de edad (80 %) y las lesiones se presentaron fundamentalmente en el párpado inferior (60 (). El eritema palpebral y el dolor en el sitio de la inyección constituyeron los eventos adversos oculares más frecuentes (95,0 y 70,0 % respectivamente) y se presentaron en el 95 % de los pacientes investigados. Los eventos adversos sistémicos (fiebre, artralgia y la cefalea) prevalecieron en el 100 % de los casos, en quienes el grado de severidad fue leve. Conclusiones: El HeberFERON( en el tratamiento del carcinoma basal palpebral es una buena alternativa no quirúrgica; es seguro y bien tolerado.

SUMMARY INTRODUCTION Interferons have been used to treat basal cell carcinoma with positive results. Cuba’s Genetic Engineering and Biotechnology Center developed HeberPAG, a combined formulation of interferons alpha-2b and gamma, for treatment of basal cell carcinoma of any size, subtype and location. OBJECTIVE Evaluate the safety and effectiveness of using Heber-PAG in primary care to treat basal cell carcinomas. METHODS A descriptive observational study was conducted of basal cell carcinoma treated with HeberPAG. The sample comprised 21 tumors in 19 patients who met selection criteria. The dose was 3.5 million international units of antiviral activity administered by perilesional infiltration 3 times a week for 3 weeks. Clinical monitoring and laboratory testing of patients was conducted before treatment initiation and at 4, 8, 16 and 52 weeks. Variables recorded were: age, sex, skin phototype, clinical and histologic type, clinical response to treatment, changes in tumor diameters and adverse events. Four response categories were included: complete response, partial response, stable disease and progressive disease. Data were recorded in medical dossiers. Microsoft Excel and SAS were used for data management and calculation of measures of frequency, central tendency and dispersion. RESULTS Of 19 patients studied, 63% were male, and 63% aged 61–80 years. At 16 weeks, there was an objective response in 76% of tumors (8 complete and 8 partial responses). Fewer objective responses were seen in rodent ulcer, advanced invasive and sclerosing clinical types and in the sclerodermiform histologic type. Mean sum of diameters decreased from 36.9 mm (SD 4.1 mm) to 10.3 mm (SD 18.3 mm). One-year recurrence was 10%. The most common adverse reaction was flu-like syndrome, consisting of fever, malaise, joint pain and muscle pain. CONCLUSIONS Basal cell carcinoma can be successfully treated in primary care settings with a combination of interferons alpha-2b and gamma administered by trained personnel. At the dose employed in this study, the formulation produces a favorable response in basal cell carcinomas of low clinical and histologic risk, and is well tolerated, with only mild side effects. CONTRIBUTION OF THIS RESEARCH This study demonstrates the feasiblity of treating basal cell carcinoma in primary care settings with a combined formulation of interferons alpha-2b and gamma, enabling management in primary care of a cancer usually treated in hospital.