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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2023.tde-04082023-152743
Document
Author
Full name
Lucila Soares da Silva Rocha
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2023
Supervisor
Committee
Riechelmann, Rachel Simões Pimenta (President)
Diz, Maria Del Pilar Estevez
Karnakis, Theodora
Pereira, Allan Ândresson Lima
Title in Portuguese
Estudo prospectivo observacional dos efeitos da quimioterapia paliativa em pacientes com câncer colorretal metastático ou irressecável com performance status comprometido
Keywords in Portuguese
Câncer colorretal
Fragilidade
Metástase tumoral
Oxaliplatina
Quimioterapia
Abstract in Portuguese
O câncer colorretal é o segundo mais incidente em homens e mulheres, excluindo-se neoplasias de pele não melanoma e por esta razão é de grande interesse seu estudo em oncologia. Com frequência a neoplasia maligna de cólon e reto se apresenta metastática, irressecável ou recorre desta maneira nos primeiros anos de acompanhamento. Apesar de diversos estudos avaliando tratamento desta neoplasia no cenário metastático com grandes avanços na última década, pouco se sabe, ainda, do benefício de tratamento padrão em pacientes que se apresentam, ao diagnóstico, com performance status (PS) comprometido, Eastern Cooperative Oncology Group (ECOG) PS 3 e 4, já que são sistematicamente excluídos dos estudos clínicos. O objetivo do presente estudo é avaliar o benefício do tratamento de primeira linha do câncer colorretal metastático com quimioterapia baseada em oxaliplatina em pacientes frágeis ECOG PS 3 e 4. Trata-se de coorte prospectiva observacional cujo desfecho primário é melhora de sintomas pela escala de sintomas de Edmonton (ESAS-r) quando se compara a situação basal com quarta semana de tratamento, excluindo-se aqueles que apresentaram toxicidades maior ou igual a grau 3, avalia como desfechos secundários qualidade de vida pelo questionário EQ5D, melhora clínica subjetiva, toxicidades, resposta bioquímica, radiológica, melhora de ECOG PS e sobrevida. Apesar de dificuldade em recrutamento não atingindo a amostra calculada, o estudo trouxe os seguintes resultados: todos os pacientes apresentaram queda de 2 pontos no pior sintoma da ESAS-r e, ao excluir aqueles com toxicidade maior ou igual a grau 3, 42,85 % atingiram o desfecho primário de eficácia, porém chama a atenção uma taxa de toxicidade grau 5 (óbito pelo tratamento) de 17,8% muito elevada neste cenário. Os resultados geram reflexões importantes já que pacientes ECOG PS 4 tiveram sobrevida global mediana de 33 dias, contra 98 dias para ECOG PS 3, p: 0,033, pacientes internados e com bilirrubina elevada parecem ter menor benefício. Por último chama a atenção a taxa de pacientes que receberam quimioterapia nas últimas duas semanas de vida (25%) e aqueles que receberam nos últimos 30 dias de vida (53,6%). Para qualidade de vida também houve melhora na percepção geral de saúde e no utility calculado, sem diferença nos quesitos individuais e com 46% dos pacientes não respondendo a reavaliação da quarta semana por óbito ou piora clínica. Apesar de uma amostra reduzida, pela fragilidade destes pacientes, o estudo levanta a necessidade de se avaliar melhor o benefício de tratamento nesta população já que, apesar do potencial impacto em sintomas, o tratamento acarreta risco muito elevado de toxicidades e em determinados subgrupos ausência de benefício em sobrevida global
Title in English
Prospective observational study of the effects of palliative chemotherapy in patients with unresectable or metastatic colorectal cancer with compromised performance status
Keywords in English
Chemotherapy
Colorectal neoplasms
Frailty
Neoplasm metastasis
Oxaliplatin
Abstract in English
Colorectal cancer is the second most common cancer in both men and women, excluding non-melanoma skin cancers, and is therefore of great interest for study in oncology. The malignant neoplasm of the colon and rectum often presents as metastatic, unresectable, or recurrent in the first few years of follow-up. Despite numerous studies evaluating treatment for this neoplasm in the metastatic scenario with significant advancements in the last decade, limited knowledge about the benefit of standard treatment in patients who present, at diagnosis, with compromised performance status (PS), Eastern Cooperative Oncology Group (ECOG) PS 3 and 4, systematically excluded from clinical trials. This study aims to evaluate the benefit of first-line treatment for metastatic colorectal cancer with oxaliplatin-based chemotherapy in fragile ECOG PS 3 and 4 patients. We conducted a prospective observational cohort whose primary outcome is symptom improvement using the Edmonton Symptom Assessment System scale (ESAS-r) when comparing the baseline situation with the fourth week of treatment, excluding those who had toxicity greater than or equal to grade 3, and evaluating the quality of life using the EQ5D questionnaire, subjective clinical improvement, toxicity, biochemical and radiological response, improvement of ECOG PS, and survival as secondary outcomes. Although recruitment was difficult and did not reach the calculated sample, the study had the following results: all patients showed a 2-point decline in the worst symptom of the ESAS-r, excluding those with toxicity greater than or equal to grade 3, 42.85% reached the primary outcome of efficacy. However, the grade 5 toxicity rate of 17.8% (death from treatment) was very high. The results raise relevant considerations since ECOG PS 4 patients had a median overall survival of 33 days, compared to 98 days for ECOG PS 3, p: 0.033, patients who were hospitalized and with elevated bilirubin seemed to have less benefit. Finally, the rate of patients receiving chemotherapy in the last two weeks of life (25%) and those who received it in the last 30 days (53.6%) is noteworthy. For the quality of life, there was also an improvement in the overall perception of health, and in the calculated utility, with no difference in individual items, but with 46% of patients not responding to the fourth-week reevaluation due to death or clinical deterioration. Despite a reduced sample, given the fragility of these patients, the study highlights the need better to evaluate the benefit of treatment in this population, as although there is a potential impact on symptoms, the treatment carries a very high risk of toxicity. In specific subgroups, there is no benefit in overall survival
 
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Publishing Date
2023-08-15
 
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