Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy.

BACKGROUND: Over-expression of epidermal growth factor receptor in esophageal cancer is associated with poor prognosis. The present study was conducted to evaluate safety and preliminary efficacy of nimotuzumab, a humanized anti-EGFR antibody in combination with radiation and chemotherapy in advanced esophageal tumours. PATIENTS AND METHODS: A Phase II clinical trial was conducted, where patients received cisplatin, 5-fluorouracil, and radiotherapy, either alone or combined with six weekly infusions of nimotuzumab at the dose of 200 mg. Safety was the primary endpoint. The antitumoral objective response rate was the secondary endpoint. Epidermal growth factor receptor expression, KRAS mutation status and anti-idiotypic response were also evaluated. RESULTS: Sixty-three patients were included in the study. Thirty patients were entered into the control group, and thirty-three patients received the treatment with nimotuzumab. The antibody was very well tolerated. Objective response rate was 47.8 % (nimotuzumab group) and 15.4 % (control group). Disease control rate was 60.9 % (nimotuzumab group) and 26.9 % (control group). Response and disease control rate were higher in patients with EGFR overexpressing tumors. CONCLUSION: Nimotuzumab plus chemoradiotherapy was safe and provided statistically significant objective response. A Phase III in patients with similar characteristics will be launched.

Risk factors for anastomotic leakage after preoperative chemoradiation therapy and low anterior resection with total mesorectal excision for locally advanced rectal cancer.

BACKGROUND: Risk factors for anastomotic leakage after preoperative chemoradiation plus low anterior resection and total mesorectal excision remain uncertain. OBJECTIVE: To analyze, the associated risk factors with colorectal anastomosis leakage following preoperative chemo-radiation therapy and low anterior resection with total mesorectal excision for rectal cancer. MATERIALS AND METHODS: Between January 1992 and December 2000, 92 patients with rectal cancer were treated with 45 Gy of preoperative radiotherapy and bolus infusion of 5-FU 450 mg/m2 on days 1-5 and 28-32, six weeks later low anterior resection was performed. Univariate analysis was performed as to find the risk factors for colorectal anastomotic leakage. RESULTS: There were 48 males and 44 females, mean age was 55.8 years. Mean tumor location above the anal verge was 7.4 +/- 2.6 cm. Preoperative mean levels of albumin and lymphocytes were 3.8 g/dL and 1,697/microL, respectively. Mean distal margin was 2.9 +/- 1.4 cm. Multivisceral resection was performed in 11 patients (13.8%), 32 patients (35%) had diverting stoma. Mean preoperative hemorrhage was 577 +/- 381 mL, and 27 patients (24%) received blood transfusion. Ten patients (10.9%) had anastomotic leakage. No operative mortality occurred. Risk factors for anastomotic leakage were: gender (male) and tumor size > 4 cm. Three patients of the group without colostomy required a mean of six days in the unit of intensive care; mean time of hospital stay of patients with and without protective colostomy was 12.4 +/- 4.5 days vs. 18.3 +/- 5.2 days (p = 0.01). CONCLUSION: In male patients with rectal adenocarcinoma measuring > 4 cm, treated by preoperative chemoradiotherapy + low anterior resection with total mesorectal excision, a diverting stoma should be performed to avoid major morbidity due to anastomotic leak.

Risk factors for anastomotic leakage after preoperative chemoradiation therapy and low anterior resection with total mesorectal excision for locally advanced rectal cancer / Factores de riesgo para la fuga anastomótica después de quimio-radioterapia preoperatoria y resección anterior baja con excisión total de mesorrecto para cáncer de recto localmente avanzado

Background. Risk factors for anastomotic leakage after preoperative chemoradiation plus low anterior resection and total mesorectal excision remain uncertain. Objective. To analyze, the associated risk factors with colorectal anastomosis leakage following preoperative chemo-radiation therapy and low anterior resection with total mesorectal excision for rectal cancer. Materials and methods. Between January 1992 and December 2000, 92 patients with rectal cancer were treated with 45 Gy of preoperative radiotherapy and bolus infusion of 5-FU 450 mg/m² on days 1-5 and 28-32, six weeks later low anterior resection was performed. Univariate analysis was performed as to find the risk factors for colorectal anastomotic leakage. Results. There were 48 males and 44 females, mean age was 55.8 years. Mean tumor location above the anal verge was 7.4 ± 2.6 cm. Preoperative mean levels of albumin and lymphocytes were 3.8 g/dL and l,697/mL, respectively. Mean distal margin was 2.9 ± 1.4 cm. Multivisceral resection was performed in 11 patients (13.8%), 32 patients (35%) had diverting stoma. Mean preoperative hemorrhage was 577 ± 381 mL, and 27 patients (24%) received blood transfusion. Ten patients (10.9%) had anastomotic leakage. No operative mortality occurred. Risk factors for anastomotic leakage were: gender (male) and tumor size > 4 cm. Three patients of the group without colostomy required a mean of six days in the unit of intensive care; mean time of hospital stay of patients with and without protective colostomy was 12.4 ± 4.5 days vs. 18.3 ± 5.2 days (p = 0.01). Conclusion. In male patients with rectal adenocarcinoma measuring > 4 cm, treated by preoperative chemoradiotherapy + low anterior resection with total mesorectal excision, a diverting stoma should be performed to avoid major morbidity due to anastomotic leak.

Antecedentes. Los factores de riesgo para la fuga de anastomosis colo-rectal después de quimio-radioterapia preoperatoria con excisión total de mesorrecto permanecen aún inciertos. Objetivo. Analizar los factores de riesgo asociados con la fuga o filtración de anastomosis colorrectal que sigue a la terapia de radiación química y a la extirpación anterior baja con total excisión mesorrectal para el cáncer rectal. Materiales y métodos. Entre enero de 1992 y diciembre de 2000, 92 pacientes con cáncer rectal fueron tratados con 45 Gy de radioterapia preoperativa e infusión del bolo de 5'FU450 mg/m² administrados los días 1-5 y del 28-32; seis semanas más tarde, se realizó la extirpación anterior baja. Se llevó a cabo un análisis univariado en cuanto a encontrar los factores de riesgo de la fuga anastomótica colorrectal. Resultados. Se trató a 48 varones y 44 mujeres cuya media etaria fue de 55.8 años. La localización media del tumor arriba del borde anal fue de 7.4 ± 2.6 cm. Los niveles medios preoperativos de albúmina y linfocitos fueron de 3.8 g/dL y 1,697/mL, respectivamente. El margen distal medio fue de 2.9 ± 1.4 cm. La extirpación multivisceral fue realizada en 11 pacientes (13.8%); 32 pacientes (35%) tuvieron una colostomía derivativa. La hemorragia preoperativa media fue de 577 ± 381 mL, y 27 pacientes (24%) recibieron transfusión sanguínea. Diez pacientes (10.9%) tuvieron fuga anastomótica. No hubo ningún deceso quirúrgico. Los factores de riesgo para la fuga anastomótica fueron: el género (masculino) y el tamaño del tumor > 4 cm. Tres pacientes del grupo sin colostomía requirieron una media de seis días en la UTI (Unidad de Terapia Intensiva); el promedio media de la duración hospitalaria de pacientes con y sin colostomía protectiva fue de 12.4 ± 4.5 días contra 18.3 ± 5.2 días (p = 0.01). Conclusión. En pacientes masculinos con adenocarcinoma rectal que mide > 4 cm, tratados mediante radioterapia química preoperativa + extirpación anterior baja con excisión total mesorrectal, debería realizarse una abertura que se desvíe a fin de evitar una mayor mortalidad debida a fuga anastomótica.