Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer.

PURPOSE: The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS: Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate. RESULTS: Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %. CONCLUSION: These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.

[Prognostic significance of metastatic lymph node ratio in colorectal cancer].

OBJECTIVE: To investigate the prognostic significance of metastatic lymph node ratio in patients with colorectal cancer. METHODS: The clinicopathological data of 303 surgically treated patients with colorectal cancer were retrospectively analyzed. Spearman correlation analysis was used to determine the correlation coefficient. The survival was analyzed using Kaplan-Meier method, and the survival difference was assessed by Log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model in forward stepwise regression. Receiver working characteristic curve was used to compare the accuracy of the metastatic lymph nodes ratio in predicting the death of patients at 5 years postoperatively with that of the number of metastatic lymph nodes. RESULTS: The MLR was not correlated with the total number of dissected lymph nodes (Spearman correlation coefficient: -0.099, P > 0.05), but the positive rate of metastatic lymph nodes did (correlation coefficient: 0.107, P < 0.05). Kaplan-Meier survival analysis revealed that the MLR significantly influenced the postoperative survival time (Log-rank chi(2) = 42.878, P < 0.01), even in the patients with less than 12 resected lymph nodes. The 5-year survival rates for rN0, rN1, rN2 and rN3 were 90.9%, 68.9%, 54.7% and 39.4%, respectively. There was a significant difference between the different stages (P < 0.01). Cox proportional hazard regression model analysis showed that the metastatic lymph node ratio was an independent prognostic factor. (EXP(B) = 7.809, P < 0.01). There was no significant difference between metastatic lymph node ratio and the number of metastatic lymph nodes in predicting the death of patients at 5 years postoperatively based on the area under the receiver working characteristic curve. CONCLUSION: The metastatic lymph node ratio in colorectal cancer patients is not correlated with the total number of dissected lymph nodes. The metastatic lymph node ratio is a major independent prognostic factor for patients with colorectal cancer. The ability of metastatic lymph node ratio in predicting the death of colorectal cancer patients at 5 years postoperatively is the same as that of the number of metastatic lymph nodes.

[Differential expression of guanylin in colorectal cancer].

OBJECTIVE: To investigate the expression of guanylin in colorectal cancer. METHODS: The expression of guanylin was examined by RT-PCR and semiquantitative analysis in 20 cases of colorectal cancer, and its relationship with clinical characteristics was analyzed. RESULTS: The positive expression of guanylin in normal tissue (80%, 16/20) was significantly higher than that in tumor tissue (35%, 7/20) (P<0.01). The same result was found in the semiquantitative analysis of 14 cases with differential expression. Differential expression of guanylin in colorectal cancer was associate with TNM stage (P<0.05), not with sex, Borrmann type and degree of differentiation (all P>0.05). CONCLUSION: There is differential expression of guanylin in colorectal cancer, and this kind of differential expression is associated with tumor TNM stage.