RESUMO
PURPOSE: Cancer-related fatigue (CRF) is a common symptom among patients with cancer. The efficacy of placebo, however, was never the main objective of any meta-analysis. Predicting the efficacy of placebo may facilitate researchers in designing future clinical trials for the treatment of CRF. METHODS: We performed a systematic review searching for prospective clinical trials comparing any treatment versus placebo for the treatment of CRF. We included studies that enrolled patients with any primary site of neoplasia and any stage of cancer. We excluded all studies that assessed fatigue related to any treatment. The primary endpoint of this study is the mean effect of placebo on fatigue according to the Functional Assessment of Chronic Illness (FACIT-F) and Brief Fatigue Inventory (BFI) scales. The secondary endpoint was the proportion of patients who reported improvement in fatigue (response rate). RESULTS: We found 520 studies, and 29 studies with 3758 participants were included in the meta-analysis. Placebo had a mean effect of + 4.88 (95%CI + 2.45 to + 7.29) using the FACIT-F scale, although it was statistically worse than the interventions studied (p = 0.005). Using the BFI scale, placebo had an average effect of + 0.64 (95%CI + 0.02 to + 1.30), although it was also worse than the other interventions studied (p = 0.002). In terms of the response rate, 29% (95%CI 25-32%) of patients taking a placebo reported a significant improvement in CRF compared with 36% of patients treated with other interventions (p = 0.030). CONCLUSIONS: Placebo treatments had a significant effect on CRF, and predicting these effects may help design future studies for CRF.
Assuntos
Fadiga/etiologia , Fadiga/terapia , Neoplasias/complicações , Efeito Placebo , Doença Crônica , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Humanos , Neoplasias/terapia , Modalidades de Fisioterapia , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: - Human epidermal growth factor receptor 2 (EGFR2/HER2/ErbB2) is a transmembrane receptor that stimulates cell proliferation when activated. The correlation of HER2 expression with prognosis has been studied in many cancer types. However, its relationship with survival of patients with metastatic gastric cancer remains unknown. Moreover, there is a lack of information on this issue in a Brazilian population. OBJECTIVE: - To assess the proportion of patients whose tumor cells express HER2 and correlate this with clinical characteristics as well as treatment outcomes. METHODS: - This was a retrospective study. We included adult patients with metastatic gastric cancer treated at an University Hospital between 2011 and 2015. Patients did not receive anti-HER2 therapy. Receptor expression was evaluated by immunohistochemistry. Survival risk factors were assessed individually with univariate Cox regression, and a P value <0.05 was considered statistically significant. RESULTS: - Forty-nine patients were included in this study. However, only 32 had samples assessed for HER2 expression. Five (16%) patients were positive. Among HER2-negative patients, the average age was 54 years, 44% received a treatment protocol with three drugs, 70% had a performance status score 0-1, and 41% had well or moderately differentiated histology. Among HER2-positive patients, the average age was 58 years, 40% received three drugs, 100% had a performance status score 0-1, and 67% had well or moderately differentiated histology. Response rate was evaluated in 28 cases, and there was no difference between the groups (HER2-negative 52% vs. HER2-positive 40%; P=0.62). Survival outcomes were numerically worse among HER2-positive patients. Median progression-free survival was 8.3 months for HER2-positive patients and 10.6 months for HER2-negative patients (HR 1.61, 95% CI: 0.59-4.38); median overall survival was 14.8 months and 16.9 months for HER2-positive and HER2-negative patients, respectively (HR 1.52, 95% CI: 0.50-4.66). CONCLUSION: - HER2 overexpression in metastatic gastric cancer patients may be a predictor of poor prognosis and further validation is warranted.
Assuntos
Receptor ErbB-2/sangue , Neoplasias Gástricas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do TratamentoRESUMO
ABSTRACT Background - Human epidermal growth factor receptor 2 (EGFR2/HER2/ErbB2) is a transmembrane receptor that stimulates cell proliferation when activated. The correlation of HER2 expression with prognosis has been studied in many cancer types. However, its relationship with survival of patients with metastatic gastric cancer remains unknown. Moreover, there is a lack of information on this issue in a Brazilian population. Objective - To assess the proportion of patients whose tumor cells express HER2 and correlate this with clinical characteristics as well as treatment outcomes. Methods - This was a retrospective study. We included adult patients with metastatic gastric cancer treated at an University Hospital between 2011 and 2015. Patients did not receive anti-HER2 therapy. Receptor expression was evaluated by immunohistochemistry. Survival risk factors were assessed individually with univariate Cox regression, and a P value <0.05 was considered statistically significant. Results - Forty-nine patients were included in this study. However, only 32 had samples assessed for HER2 expression. Five (16%) patients were positive. Among HER2-negative patients, the average age was 54 years, 44% received a treatment protocol with three drugs, 70% had a performance status score 0-1, and 41% had well or moderately differentiated histology. Among HER2-positive patients, the average age was 58 years, 40% received three drugs, 100% had a performance status score 0-1, and 67% had well or moderately differentiated histology. Response rate was evaluated in 28 cases, and there was no difference between the groups (HER2-negative 52% vs. HER2-positive 40%; P=0.62). Survival outcomes were numerically worse among HER2-positive patients. Median progression-free survival was 8.3 months for HER2-positive patients and 10.6 months for HER2-negative patients (HR 1.61, 95% CI: 0.59-4.38); median overall survival was 14.8 months and 16.9 months for HER2-positive and HER2-negative patients, respectively (HR 1.52, 95% CI: 0.50-4.66). Conclusion - HER2 overexpression in metastatic gastric cancer patients may be a predictor of poor prognosis and further validation is warranted.
RESUMO Contexto - O receptor 2 do fator de crescimento epidermal humano (EGFR2/HER2/ErbB2) é um receptor transmembrana que estimula a proliferação celular quando ativado. A expressão de HER2 foi estudada em diversas neoplasias, como câncer gástrico. No entanto, sua relação com a sobrevida dos pacientes com câncer gástrico metastático permanece desconhecida. Além disso, há falta de informação sobre este assunto na população brasileira. Objetivo - Avaliar a proporção de pacientes cujas células tumorais expressam HER2 e correlacionar essa característica com aspectos clínicos e também com os desfechos do tratamento. Métodos - Este é um estudo retrospectivo. Foram incluídos pacientes adultos com câncer gástrico metastático tratados em um Hospital Geral Universitário entre 2011 e 2015. Nenhum paciente recebeu terapia anti-HER2. A expressão do receptor foi avaliada por imuno-histoquímica. Fatores de risco para a sobrevida foram avaliados com regressão de Cox univariada e valor P<0,05 foi considerado estatisticamente significativo. Resultados - Quarenta e nove pacientes foram incluídos neste estudo. No entanto, 32 tiveram amostras avaliadas para expressão de HER2. Cinco (16%) pacientes foram positivos. Entre os pacientes HER2 negativos: a idade média foi de 54 anos, 44% receberam um protocolo com três drogas, 70% apresentavam um score de status performance 0-1, 41% tinham histologia bem ou moderada diferenciada. Entre os pacientes HER2 positivos: a média de idade foi de 58 anos, 40% receberam três drogas, 100% apresentavam um score de status performance de 0-1, 67% tinham histologia bem ou moderada diferenciada. A taxa de resposta foi avaliada em 28 casos e não houve diferença entre os grupos (HER2 negativo 52% e HER2 positivo de 40%; P=0,62). A sobrevida foi menor entre pacientes HER2 positivos. As medianas de Sobrevida Livre de Progressão foram 8,3 meses e 10,6 meses, respectivamente (HR 1,61; IC 95%: 0,59-4,38). As medianas de Sobrevida Global foram 14,8 meses e 16,9 meses, respectivamente (HR 1,52; IC 95%: 0,50-4,66). Conclusão - A expressão tumoral de HER2 pode ser um fator de pior prognóstico para pacientes portadores de câncer gástrico metastático e uma validação futura desses achados se faz necessária.