Eficácia e segurança da nicotinamida 5% creme na estabilização do campo de cancerização cutâneo: um ensaio clínico randomizado, duplo-cego e placebo-controlado
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Data
2023-01-26
Autores
Martins, Ivanka Miranda de Castro
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Universidade Estadual Paulista (Unesp)
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Fundamentos: O campo de cancerização cutâneo (CCC) é uma área que possui alterações genômicas e subclínicas decorrentes da exposição solar crônica, com maior predisposição ao desenvolvimento de lesões pré-neoplásicas e neoplásicas. As queratoses actínicas (QAs) são consideradas marcadores de atividade dessa área. Tratamentos que visem à estabilização do campo podem reduzir a incidência de QAs e de tumores cutâneos. A nicotinamida (NIC), também conhecida como niacinamida, possui efeito na quimioprevenção do câncer de pele, pois atua no reparo do DNA, diminui a inflamação, reprime a depleção de energia celular e reduz os efeitos da imunossupressão cutânea causados pela radiação ultravioleta. Esse trabalho objetivou avaliar a eficácia e segurança do creme de NIC 5% na estabilização do campo de cancerização cutâneo, em imunocompetentes. Casuística e métodos: Ensaio clínico randomizado, duplo-cego e placebo controlado para avaliar a eficácia e segurança da NIC 5% creme na estabilização no campo de cancerização. Foram incluídos 26 pacientes imunocompetentes do ambulatório de Dermatologia da FMB-UNESP, com 3-10 QAs em cada antebraço. Após a inclusão, foi realizada criocirurgia com nitrogênio líquido, por 10 segundos, nas QAs de ambos os antebraços, randomizados para receber, após 14 dias da realização da criocirurgia, uma das seguintes intervenções: NIC 5% creme, duas vezes por dia durante 56 dias; ou placebo (PLAC), na mesma posologia. Para cada paciente, o estudo teve duração de 70 dias e, durante esse tempo, foram fornecidos tubos de filtro solar de amplo espectro FPS 30 (Loreal Solar Expertise Supreme®) para aplicação em ambos os antebraços. Todos os pacientes foram reavaliados após 28 e 70 dias. A avaliação clínica foi realizada pela contagem de QAs, escala de gravidade das queratoses actínicas (EGQA), escala de fotoenvelhecimento dos antebraços (EFA) e questionário sobre efeitos adversos e tolerabilidade. O desfecho primário foi a redução percentual da contagem de QAs no D70. Os desfechos secundários foram: o clearance completo das lesões, redução da atividade do CCC, analisada pelo EGQA e EFA no D70. Todos os participantes incluídos no estudo fizeram parte da população ITT (intention to treat). A contagem de QAs, EGQA e EFA foram comparadas de acordo com o tempo e os grupos por modelo linear generalizado de efeitos mistos. A significância foi definida como valor p<0,05. Resultados: Ambos os tratamentos melhoraram todos os desfechos, sem diferença entre eles. As contagens de QAs reduziram em 61% (IC95% 50 a 72%; p<0,01) para o grupo NIC; e em 56% (IC 95% 44 a 68%; p<0,01) para o grupo PLAC. O clearance completo foi atingido em 21% (IC95% 7 a 37%) dos participantes do grupo NIC, e em 17% (IC95% 4 a 31%) dos participantes do grupo PLAC (p=0,44). O uso de NIC foi bem tolerado e não houve predileção entre os tratamentos (p=0,99). Limitações: Estudo monocêntrico, interrompido na análise interina por futillidade da intervenção. Conclusão: O tratamento tópico com nicotinamida 5% creme foi seguro em idosos imunocompetentes, porém, não promoveu estabilização do campo de cancerização ou melhora do aspecto da pele comparado ao placebo, após criocirurgia.
Background: Skin field cancerization (SFC) is a skin area which has genomic and subclinical alterations, consequences of chronic sun exposure, with a greater predisposition to the development of preneoplastic and neoplastic lesions. Actinic keratoses (AKs) are considered clinical sign of activity in SFC. Treatments which aim to stabilize SFC may reduce the incidence of AK and skin cancer. Nicotinamide, also known as niacinamide (NIC), has effect on the chemoprevention of skin cancer, as it acts on DNA repair, reduces inflammation, represses cellular energy depletion and reduces the effects of cutaneous immunosuppression caused by UVR. This work aims to evaluate the efficacy and safety of 5% NIC cream in SFC stabilization in immunocompetent patients. Methods: Randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of 5% nicotinamide cream in stabilizing skin field cancerization. Twenty-six immunocompetent patients from the Dermatology outpatient clinic of FMBUNESP were included, with three up to ten AKs on each forearm. After inclusion, cryosurgery with liquid nitrogen was performed for 10 seconds on the AKs of both forearms, which were randomized to receive, two weeks after the procedure: NIC 5% cream, twice a day for 56 days; or placebo (PLAC), in the same posology. For each patient, the study lasted 70 days. SPF 30 broad-spectrum sunscreen (Loreal Solar Expertise Supreme®) were provided for application on both forearms during the time of the study. All patients were reassessed after 28 and 70 days. The clinical evaluation was performed by AK count, the actinic keratosis severity scale (AKSS), the forearms photoaging scale (FPS) and questionnaire on adverse effects and tolerability. The primary endpoint was the percentage reduction in AK count at D70. Secondary outcomes were: complete clearance of lesions, reduction of SFC activity, analyzed by AKSS and FPS on D70. All patients included in the study and randomized were part of the intention to treat population. AK count, AKSS, FPS were compared according to time and for groups (over time) by the generalized linear mixed effects model. Significance was defined as a one-tailed p-value <0.05. Results: Both treatments improved all outcomes, with no difference between them. AKs counts were reduced by 61% (95%CI 50 to 72%; p<0.01) for the NIC group; and in 56% (95% CI 44 to 68%; p<0.01) for the PLAC group. Total clearance was achieved in 21% (95%CI 7 to 37%) of participants in the NIC group, and in 17% (95%CI 4 to 31%) of participants in the PLAC group (p=0.44). The use of NIC was well tolerated and there was no predilection between treatments (p=0.99). Limitations: Single-center study, interrupted in the internal analysis due to the futility of the intervention. Conclusion: Topical treatment with 5% nicotinamide cream was safe in immunocompetent elderly people; however, it did not promote stabilization of the cancerization field or improve the appearance of the skin compared to placebo after cryosurgery.
Background: Skin field cancerization (SFC) is a skin area which has genomic and subclinical alterations, consequences of chronic sun exposure, with a greater predisposition to the development of preneoplastic and neoplastic lesions. Actinic keratoses (AKs) are considered clinical sign of activity in SFC. Treatments which aim to stabilize SFC may reduce the incidence of AK and skin cancer. Nicotinamide, also known as niacinamide (NIC), has effect on the chemoprevention of skin cancer, as it acts on DNA repair, reduces inflammation, represses cellular energy depletion and reduces the effects of cutaneous immunosuppression caused by UVR. This work aims to evaluate the efficacy and safety of 5% NIC cream in SFC stabilization in immunocompetent patients. Methods: Randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of 5% nicotinamide cream in stabilizing skin field cancerization. Twenty-six immunocompetent patients from the Dermatology outpatient clinic of FMBUNESP were included, with three up to ten AKs on each forearm. After inclusion, cryosurgery with liquid nitrogen was performed for 10 seconds on the AKs of both forearms, which were randomized to receive, two weeks after the procedure: NIC 5% cream, twice a day for 56 days; or placebo (PLAC), in the same posology. For each patient, the study lasted 70 days. SPF 30 broad-spectrum sunscreen (Loreal Solar Expertise Supreme®) were provided for application on both forearms during the time of the study. All patients were reassessed after 28 and 70 days. The clinical evaluation was performed by AK count, the actinic keratosis severity scale (AKSS), the forearms photoaging scale (FPS) and questionnaire on adverse effects and tolerability. The primary endpoint was the percentage reduction in AK count at D70. Secondary outcomes were: complete clearance of lesions, reduction of SFC activity, analyzed by AKSS and FPS on D70. All patients included in the study and randomized were part of the intention to treat population. AK count, AKSS, FPS were compared according to time and for groups (over time) by the generalized linear mixed effects model. Significance was defined as a one-tailed p-value <0.05. Results: Both treatments improved all outcomes, with no difference between them. AKs counts were reduced by 61% (95%CI 50 to 72%; p<0.01) for the NIC group; and in 56% (95% CI 44 to 68%; p<0.01) for the PLAC group. Total clearance was achieved in 21% (95%CI 7 to 37%) of participants in the NIC group, and in 17% (95%CI 4 to 31%) of participants in the PLAC group (p=0.44). The use of NIC was well tolerated and there was no predilection between treatments (p=0.99). Limitations: Single-center study, interrupted in the internal analysis due to the futility of the intervention. Conclusion: Topical treatment with 5% nicotinamide cream was safe in immunocompetent elderly people; however, it did not promote stabilization of the cancerization field or improve the appearance of the skin compared to placebo after cryosurgery.
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Palavras-chave
Campo de cancerização, Carcinoma espinocelular, Ceratose actínica, Dermatologia, Niacinamida, Oncologia, Skin field cancerization, Squamous cell carcinoma, Actinic keratosis, Niacinamide, Dermatology, Oncology, Chemoprevention