Gilberto de Castro Junior1, José Getúlio Segalla2, Sérgio Jobim de Azevedo3, Carlos José Andrade4, Daniel Grabarz5, Bruno de Araújo Lima França6, Auro Del Giglio7, Nicolas Silva Lazaretti8, Maria Nunes Álvares9, José Luiz Pedrini10, Celio Kussumoto11, João Nunes de Matos Neto12, Nora Manoukian Forones13, Hezio Jadir Fernandes Júnior14, Giuliano Borges15, Gustavo Girotto16, Ismael Dale Cotrim Guerreiro da Silva17, Fauze Maluf-Filho18, Nils Gunnar Skare19. 1. Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil. Electronic address: gilberto.castro@usp.br. 2. Hospital Amaral Carvalho, Jaú, Brazil. Electronic address: segalla@amaralcarvalho.org.br. 3. Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. Electronic address: sazevedo@hcpa.ufrgs.br. 4. Instituto Nacional de Câncer, Rio de Janeiro, Brazil. Electronic address: carlosj@inca.gov.br. 5. Hospital de Mogi das Cruzes, Mogi das Cruzes, Brazil. Electronic address: dgrabarz@bol.com.br. 6. Hospital Geral de Bonsucesso, Rio de Janeiro, Brazil. Electronic address: balf.dr@gmail.com. 7. Faculdade de Medicina do ABC, Santo André, Brazil. Electronic address: auro@cepho.org.br. 8. Hospital da Cidade de Passo Fundo, Passo Fundo, Brazil. Electronic address: nicolaslazaretti@yahoo.com.br. 9. Santa Casa de Belo Horizonte, Belo Horizonte, Brazil. Electronic address: mnalvares@terra.com.br. 10. Hospital Nossa Senhora Conceição, Porto Alegre, Brazil. Electronic address: jose.pedrini@hotmail.com. 11. Hospital Municipal São José, Joinville, Brazil. Electronic address: celio@cho-joi.com.br. 12. Hospital Universitário de Brasília, Brasília, Brazil. Electronic address: jnunes@cettro.com.br. 13. Universida de Federal de São Paulo, São Paulo, Brazil. Electronic address: noraforones@gmail.com. 14. Consultoria em Estudos de Investigação, São Caetano do Sul, Brazil; Instituto do Câncer Arnaldo Vieira de Carvalho, São Paulo, Brazil. Electronic address: hezio@uol.com.br. 15. Centro de Itajaí, Itajaí, Brazil. Electronic address: giuliano_borges@yahoo.com.br. 16. Hospital de Base, São José do Rio Preto, Brazil. Electronic address: oncofamerp@yahoo.com.br. 17. Universida de Federal de São Paulo, São Paulo, Brazil. Electronic address: ismael.dale@gmail.com. 18. Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil. Electronic address: fauze.maluf@terra.com.br. 19. Hospital Erasto Gaertner, Curitiba, Brazil. Electronic address: ngskare@onda.com.br.
Abstract
PURPOSE:Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated. RESULTS: We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm. CONCLUSION:Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL. CLINICAL TRIALS: Identification number: EF024-201; Trial registry: NCT01249352.
RCT Entities:
PURPOSE: Chemoradiotherapy is the standard treatment for patients with inoperable locally advanced oesophageal cancer. We sought to assess the safety and efficacy of chemoradiation combined with nimotuzumab, a humanised antibody directed against epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Untreated patients with inoperable locally advanced oesophageal cancer and no distant metastases were randomised to chemoradiotherapy (cisplatin and fluorouracil combined with external beam radiation) alone or in combination with nimotuzumab. The primary end-point was the endoscopic complete response (eCR) rate, and secondary end-points comprised quality of life (QoL) and safety. The combined eCR and pathologic complete response (cEPCR) and overall survival (OS) were also evaluated. RESULTS: We enrolled 107 patients with a mean age of 59 years, and 93% had squamous cell carcinoma. Toxicity was manageable in both arms with no important differences in adverse events (AEs). We performed post-treatment endoscopies in 67 patients, including 60 who had a biopsy. In the intent-to-treat population, the eCR rates with and without nimotuzumab were 47.2% and 33.3% (P = 0.17), respectively, and the cEPCR rates were 62.3% and 37.0% (P = 0.02), respectively. With a median follow-up of 14.7 months, the hazard ratio (HR) for OS was 0.68 (95% confidence interval (CI): 0.44-1.07; P = 0.09) with a median OS of 15.9 months for the nimotuzumab arm and 11.5 months for the control arm. Regarding QoL, a significant difference was observed for the physical subscale score (P = 0.03) with lower values for the control arm. CONCLUSION: Combined chemoradiotherapy plus nimotuzumab is safe for patients with locally advanced oesophageal cancer, it appears to increase the cEPCR rate, and without compromising QoL. CLINICAL TRIALS: Identification number: EF024-201; Trial registry: NCT01249352.
Authors: Ming Bai; Meng Wang; Ting Deng; Yuxian Bai; Kai Zang; Zhanhui Miao; Wenlin Gai; Liangzhi Xie; Yi Ba Journal: Cancer Biol Med Date: 2022-01-12 Impact factor: 4.248