Estudo comparativo sobre o emprego de 5-fluoruracil a 5% em creme versus sua utilização como agente de peelings superficiais seriados no tratamento do fotoenvelhecimento avançado
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Arquivos
Data
2013-05-29
Autores
Guimarães, Carolina Okada Zerbini [UNIFESP]
Orientadores
Bagatin, Edileia [UNIFESP]
Tipo
Tese de doutorado
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Introdução: O 5-fluorouracil (5-FU) é um agente quimioterápico antimetabólito que atua bloqueando a reação de metilação do ácido deoxiuridílico em ácido timidílico, interferindo na síntese do DNA e RNA. A deficiência de timina provoca desequilíbrio no crescimento e morte celular. O uso tópico de 5-FU a 5% em creme é aprovado para o tratamento de queratoses actínicas. Outra modalidade de emprego são os peelings superficiais seriados. Observa-se melhora da textura, rugas e pigmentação da pele com fotodano avançado. Assim, é útil na prevenção das queratoses actínicas e câncer de pele não-melanoma, com benefício na aparência da pele. Objetivos: O objetivo primário foi avaliar a eficácia (clínica e histológica) e a segurança do 5-FU 5% em creme comparado ao seu uso em peelings seriados no tratamento do fotodano avançado dos antebraços. O objetivo secundário foi avaliar o benefício estético na pele fotoenvelhecida relacionado à melhora das alterações epidérmicas e dérmicas, assim como a duração dos resultados. Métodos: Estudo de intervenção terapêutica, randomizado, comparativo, avaliador-cego, em 32 homens e mulheres, acima de 50 anos, portadores de fotoenvelhecimento moderado a grave dos antebraços. Os esquemas terapêuticos compreenderam o uso do 5-FU 5% em creme, uma vez ao dia, por quatro semanas, num antebraço e a realização de quatro peelings de 5-FU seriados semanais no antebraço contralateral. A avaliação da eficácia foi clínica, através de uma escala de fotoenvelhecimento desenvolvida para antebraços, opinião do paciente e investigador e fotográfica cega, por três observadores. Foram realizadas três biópsias de pele em cada antebraço (pré, um mês e seis meses póstratamentos) e exame histopatológico, pelas colorações hematoxilina-eosina e Calleja (fibras elásticas), além de imuno-histoquímica para avaliar a expressão da proteína p53 epidérmica não selvagem e marcador dérmico para procolágeno I. A avaliação de segurança baseou-se no relato e observação de eventos adversos. Resultados: Os
achados clínicos e histológicos confirmaram os benefícios do 5-FU 5% tópico, independentemente da modalidade de uso, na melhora no aspecto geral da pele fotoenvelhecida, redução do material elastótico da derme. A imuno-histoquímica demonstrou diminuição da expressão da proteína p53 e aumento da expressão do procolágeno I, sem diferenças entre os tratamentos. A avaliação clínica após seis meses demonstrou a manutenção dos efeitos observados após um mês do final dos tratamentos. Os eventos adversos observados, de intensidade leve a moderada e sem diferenças entre os tratamentos, foram: prurido, dor, eritema, xerose, descamação e crostas. Houve melhor tolerabilidade com a utilização dos peelings superficiais seriados. Conclusão: O 5-FU a 5% em creme ou peeling foi eficaz no tratamento do fotodano avançado dos antebraços, promoveu redução da expressão de p53, e reestruturação dérmica.
Background: 5-fluorouracil (5-FU) is a chemotherapeutic antimetabolite agent causing blockade of methylation reaction of deoxiuridilic acid in timidilic acid, interfering in DNA and RNA synthesis. Thymine deficiency causes an imbalance in cell growth and cell death. The topical use of 5-FU 5% cream is approved for the treatment of actinic keratosis. Another mode of use is superficial peeling series. An improvement in texture wrinkles and skin pigmentation have been noticed in photodamaged skin. Thus, it is useful to prevent the development of actinic keratosis and non-melanoma skin cancer, but also to provide benefits in skin appearance. Objectives: The primary objective was to evaluate the efficacy (clinical and histological) and safety of 5% 5-FU cream compared to its use in serial peelings in treating advanced photodamage of the forearms. The secondary objective was to evaluate the aesthetic benefit in improving photoaged skin, considering epidermal and dermal changes, as well as the duration of results. Methods: Study of therapeutic intervention, randomized, comparative, evaluator-blind, in 32 men and women, aged 50 years or older, with moderate to severe photoaging in the forearms. The treatment regimens comprised the use of 5% 5-FU cream once a day for four weeks in one forearm and four weekly sessions of 5% 5-FU peelings in the contralateral arm after randomization. The efficacy endpoint was clinical, using a photodamage scale designed for forearms, patient and investigator's opinion and photographic blind evaluation by three observers. We performed three skin biopsies in each forearm (pre, one month and six months post-treatment) with histopathological examination by hematoxylin-eosin and Calleja (elastic fibers), and immunohistochemistry to evaluate the expression of epidermal not wild (???) p53 protein and dermal marker for procollagen I. The safety assessment was based on observation and reports of adverse events. Results: The clinical and histological findings confirmed the benefits of topical 5% 5-FU, irrespective of the method of use, the improvement of the global appearance of photoaged skin and the decrease of elastotic material in dermis. Immunohistochemistry showed reduced expression of p53 protein and increased expression of procollagen I, no differences between treatments. The evaluation after six months revealed the maintenance of the beneficial effects observed one month after the end of treatment. Adverse events like pruritus, pain, erythema, xerosis, desquamation and crusts of slight or moderate intensity and no differences between treatments were observed. There was better tolerability in the use of superficial peeling series Conclusion: The 5-FU as cream or peeling was effective in the treatment of severe photoaging in the forearms, decrease the p53 expression and the dermal remodeling was confirmed.
Background: 5-fluorouracil (5-FU) is a chemotherapeutic antimetabolite agent causing blockade of methylation reaction of deoxiuridilic acid in timidilic acid, interfering in DNA and RNA synthesis. Thymine deficiency causes an imbalance in cell growth and cell death. The topical use of 5-FU 5% cream is approved for the treatment of actinic keratosis. Another mode of use is superficial peeling series. An improvement in texture wrinkles and skin pigmentation have been noticed in photodamaged skin. Thus, it is useful to prevent the development of actinic keratosis and non-melanoma skin cancer, but also to provide benefits in skin appearance. Objectives: The primary objective was to evaluate the efficacy (clinical and histological) and safety of 5% 5-FU cream compared to its use in serial peelings in treating advanced photodamage of the forearms. The secondary objective was to evaluate the aesthetic benefit in improving photoaged skin, considering epidermal and dermal changes, as well as the duration of results. Methods: Study of therapeutic intervention, randomized, comparative, evaluator-blind, in 32 men and women, aged 50 years or older, with moderate to severe photoaging in the forearms. The treatment regimens comprised the use of 5% 5-FU cream once a day for four weeks in one forearm and four weekly sessions of 5% 5-FU peelings in the contralateral arm after randomization. The efficacy endpoint was clinical, using a photodamage scale designed for forearms, patient and investigator's opinion and photographic blind evaluation by three observers. We performed three skin biopsies in each forearm (pre, one month and six months post-treatment) with histopathological examination by hematoxylin-eosin and Calleja (elastic fibers), and immunohistochemistry to evaluate the expression of epidermal not wild (???) p53 protein and dermal marker for procollagen I. The safety assessment was based on observation and reports of adverse events. Results: The clinical and histological findings confirmed the benefits of topical 5% 5-FU, irrespective of the method of use, the improvement of the global appearance of photoaged skin and the decrease of elastotic material in dermis. Immunohistochemistry showed reduced expression of p53 protein and increased expression of procollagen I, no differences between treatments. The evaluation after six months revealed the maintenance of the beneficial effects observed one month after the end of treatment. Adverse events like pruritus, pain, erythema, xerosis, desquamation and crusts of slight or moderate intensity and no differences between treatments were observed. There was better tolerability in the use of superficial peeling series Conclusion: The 5-FU as cream or peeling was effective in the treatment of severe photoaging in the forearms, decrease the p53 expression and the dermal remodeling was confirmed.
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Citação
GUIMARÃES, Carolina Okada Zerbini. Estudo comparativo sobre o emprego de 5-fluoruracil a 5% em creme versus sua utilização como agente de peelings superficiais seriados no tratamento do fotoenvelhecimento avançado. 2013. 191 f. Tese (Doutorado em Ciências) – Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2013.