Objective:To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to compare the efficacy of surgical resection followed by adjuvant radiotherapy（SR） with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival（OS） of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies. Methods:A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed. Results:A total of 108 patients were included in the study. The results of the univariate analysis showed that gender（P=0.850） had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio（PLR）, neutrophil-to-lymphocyte ratio（NLR）, T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis（P<0.05）. The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC（P<0.05）. Patients who received neoadjuvant therapy had longer OS than those who underwent SR only（P<0.001）. There was no significant difference in tumor response to the two neoadjuvant therapies and in OS（P>0.05）, and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups（P>0.05）. Conclusion:Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.
Humans ; Neoadjuvant Therapy ; Squamous Cell Carcinoma of Head and Neck ; Cetuximab/therapeutic use* ; Retrospective Studies ; China ; Prognosis ; Fluorouracil ; Head and Neck Neoplasms

Epidermal growth factor receptor (EGFR) is mutated, dysregulated or overexpressed in many epithelial malignancies, and EGFR activation has been found to be important in tumor growth and progression. Anti-EGFR monoclonal antibodies target the extracellular domain of EGFR; and show promising anti-tumor potential at clinical trials without severe side effects. In this article the pharmacokenetics and clinical study of 3 anti-EGFR monoclonal antibodies (cetuximab, panitumumab and nimotuzomab) were reviewed.
Antibodies, Monoclonal ; pharmacokinetics ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Cetuximab ; Humans ; Neoplasms ; therapy ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; immunology

Preoperative chemoradiotherapy (CRT) has become an important component of comprehensive treatment for rectal cancer. Although local recurrent risk has been remarkably reduced by CRT, distant metastasis remains the main cause of therapeutic failure. Therefore, more and more studies focused on controlling distant metastasis in order to prolong long-term survival. Recently, CRT has achieved certain progression in rectal cancer: (1)Patients with stage T3 should be classified into specific subgroups to formulate individualized treatment regimen. For stage T3a, it is feasible to perform surgery alone or administrate low intensity preoperative CRT; for stage T3b and T3c, conventional preoperative CRT should be performed in order to reduce the risk of recurrence postoperatively. (2)With regard to combined regimen for chemotherapy, oral capecitabine superiors to intravenous bolus 5-fluorouracil (5-FU) and is comparable to continuous intravenous infusion 5-FU with a better safety. Therefore, capecitabine is recommended for older patients and those with poor tolerance to chemotherapy. Compared to single 5-FU concurrent CRT, addition of oxaliplatin into preoperative CRT may result in a higher survival benefit in Chinese patients. As to the application of irinotecan, bevacizumab or cetuximab, unless there are more evidence to confirm their efficacy and safety from randomized controlled trial, they should not be recommended for adding to preoperative CRT routinely. (3)On the optimization in CRT pattern, the application values of induction chemotherapy before concurrent CRT, consolidation chemotherapy after concurrent CRT, neoadjuvant sandwich CRT, neoadjuvant chemotherapy alone and short-course preoperative radiotherapy remain further exploration. (4)On the treatment strategy for clinical complete response (cCR) after CRT, whether "wait and see" strategy is able to be adopted, it is still a hot topic with controversy.
Antineoplastic Agents ; therapeutic use ; Bevacizumab ; therapeutic use ; Camptothecin ; analogs & derivatives ; therapeutic use ; Capecitabine ; therapeutic use ; Cetuximab ; therapeutic use ; Chemoradiotherapy ; Deoxycytidine ; Fluorouracil ; therapeutic use ; Humans ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Organoplatinum Compounds ; therapeutic use ; Preoperative Care ; Rectal Neoplasms ; surgery ; therapy

Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; classification ; metabolism ; pathology ; surgery ; therapy ; Carcinoma ; classification ; metabolism ; pathology ; surgery ; therapy ; Cetuximab ; Chemotherapy, Adjuvant ; Cyclophosphamide ; therapeutic use ; Female ; Fluorouracil ; therapeutic use ; Humans ; Lymphatic Metastasis ; Methotrexate ; therapeutic use ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Trastuzumab

Antibodies, Monoclonal ; immunology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Carcinoma, Squamous Cell ; drug therapy ; Cetuximab ; Head and Neck Neoplasms ; drug therapy ; Humans ; Receptor, Epidermal Growth Factor ; immunology

OBJECTIVETo investigate the effect of anti-EGFR monoclonal antibody on the chemosensitivity of human colon cancer cells and explore the possible molecular mechanism.

METHODSThe inhibitory effect of irinotecan (CPT-11), oxaliplatin (L-OHP) and fluorouracil (5-Fu), used alone or in combination with anti-EGFR monoclonal antibody, on the proliferation of LoVo cells in vitro was assessed by MTT assay. The expressions of PI3K and Akt protein in the treated cells were examined by Western blotting, and their mRNA expressions were detected by RT-PCR.

RESULTSBoth h-R3 and C-225 treatments significantly increased the chemosensitivity of LoVo cells to irinotecan and oxaliplatin. 5-Fu and h-R3 coadministered showed a synergistic effect on the cells, but 5-Fu and C-225 had an antagonistic action. Treatment with C-225 or h-R3 resulted in lowered expressions of PI3K and Akt in LoVo cells.

CONCLUSIONAnti-EGFR monoclonal antibody can increase the chemosensitivity of human colon cancer cells to most chemotherapeutic drugs, and such effect might be attributed to the blocking of PI3K/Akt signaling pathway by these antibodies.

Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Cetuximab ; Colonic Neoplasms ; drug therapy ; metabolism ; Humans ; Oncogene Protein v-akt ; metabolism ; Receptor, Epidermal Growth Factor ; immunology ; Signal Transduction

OBJECTIVE: To-evaluate the role and clinical value of cetuximab in the treatment of head and neck squamous cell carcinoma (HNSCC), and figure out its effectiveness and application, so as to develop evidence-based recommendations for treatment. METHOD: We comprehensively searched the CBM, Pubmed, EMBASE, and the Cochrane databases to identify published studies on the effect of cetuximab in HNSCC patients. Primary outcomes included overall survival (OS), progression-free survival(PFS) and overall response rate(ORR). Secondary outcomes included serious adverse events, such as neutropenia, anemia, thrombocytopenia, skin reactions, hypokalemia, vomiting, asthenia, hypomagnesemia, dyspnea and sepsis. Results were dispalyed as risk ratio (RR), odds ratio (OR), mean difference (MD) and 95% CI. RESULT: A Meta-analysis was conducted on 4 randomized controlled trials, including 2 trials comprising 1,319 patients with locally advanced HNSCC and 2 trails comprising 559 patients with recurrent or metastatic HNSCC. For locally advanced HNSCC, the 2 year PFS and OS showed no significant differences in patients received cetuximab or not (PFS fixed effect: RR=1.02, 95%CI 0.92-1.12, P>0.05; OS fixed effect: RR=1.06, 95%CI 1.00-1.13, P>0.05, respectively). Grade 3-4 dysphagia was also similar in patients treated with cetuximab or no cetuximab (dysphagia: fixed effect: RR = 0.92; 95% CI 0.84-1.02, P>0. 05). Only grade 3-4 mucositis and skin reaction showed statistical significance between patients treated with cetuximab and patients with no cetuximab (mucositis: fixed effect: RR=1.21; 95%CI 1.07-1. 36, P<0. 05; skin reaction: fixed effect: RR=1.99; 95%CI 1.39-2.85, P<0.05, respectively). For recurrent or metastatic HNSCC, the OS overall mean difference was 2.41 (95% CI 0.96-3.86, P<0.05), the PFS overall mean difference was 2. 06 (95% CI 1.34 - 2.77, P<0.05), and the ORR overall Odds ratio was 2.38 (95% CI 1.60-3.54,P<0.05), suggesting significant effect of cetuximab in improving the prognosis of R/M HNSCC. Owing to small number of trials it was not possible to assess the presence of publication bias. Of note, the 1 year survival overall Odds ratio was 1.39 (95% CI 0.98-1.97, P>0.05). The grade 3 or 4 adverse effects were described in 83. 4% of patients in cetuximab group and 75. 5% of patients in no cetuximab group. The overall side effects risk ratio suggested statistically significant difference between patients treated with cetuximab and pa- tients with no cetuximab (RR=1.11, 95% CI 1.01-1.20, P<0.05, P =47%). CONCLUSION The 2 year progression-free survival and overall survival were similar between cetuximab group and no cetuximab group in patients with locally advanced head and neck squamous cell cancer. Data are limited and the benefits of cetuximab on this outcome remain uncertain. Impact of grade 3-4 dysphagia was similar in both groups, however, the incidence of grade 3-4 mucositis and skin reaction were lower in patients treated with cetuximab. Existing randomized controlled trials provided a scientific evidence for the use of cetuximab in R/M HNSCC. The conclusion of the study is based on limited number of RCT, so further investigation is still needed before firm recommendations of cetuximab can be made in the treatment of HNSCC.
Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; Cetuximab ; Disease-Free Survival ; Head and Neck Neoplasms ; drug therapy ; Humans ; Squamous Cell Carcinoma of Head and Neck

The NCCN has recently released its 2017 version 1.0 guideline for colorectal cancer. There are several updates from this new version guideline which are believed to change the current clinical practice. Update one, low-dose aspirin is recommended for patients with colorectal cancer after colectomy for secondary chemoprevention. Update two, biological agents are removed from the neoadjuvant treatment regimen for resectable metastatic colorectal cancer (mCRC). This update is based on lack of evidence to support benefits of biological agents including bevacizumab and cetuximab in the neoadjuvant setting. Both technical criteria and prognostic information should be considered for decision-making. Currently biological agents may not be excluded from the neoadjuvant setting for patients with resectable but poor prognostic disease. Update three, panitumumab and cetuximab combination therapy is only recommended for left-sided tumors in the first line therapy. The location of the primary tumor can be both prognostic and predictive in response to EGFR inhibitors in metastatic colorectal cancer. Cetuximab and panitumumab confer little benefit to patients with metastatic colorectal cancer in the primary tumor originated on the right side. On the other hand, EGFR inhibitors provide significant benefit compared with bevacizumab-containing therapy or chemotherapy alone for patients with left primary tumor. Update four, PD-1 immune checkpoint inhibitors including pembrolizumab or nivolumab are recommended as treatment options in patients with metastatic deficient mismatch repair (dMMR) colorectal cancer in second- or third-line therapy. dMMR tumors contain thousands of mutations, which can encode mutant proteins with the potential to be recognized and targeted by the immune system. It has therefore been hypothesized that dMMR tumors may be sensitive to PD-1 inhibitors.
Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Aspirin ; administration & dosage ; therapeutic use ; Bevacizumab ; therapeutic use ; Biological Products ; therapeutic use ; Brain Neoplasms ; drug therapy ; genetics ; Cetuximab ; therapeutic use ; Clinical Decision-Making ; methods ; Colorectal Neoplasms ; drug therapy ; genetics ; pathology ; prevention & control ; therapy ; Contraindications ; Humans ; Mutation ; physiology ; Neoadjuvant Therapy ; standards ; Neoplasm Metastasis ; drug therapy ; Neoplastic Syndromes, Hereditary ; drug therapy ; genetics ; Practice Guidelines as Topic ; Prognosis ; Secondary Prevention ; methods ; standards

OBJECTIVETo summarize our experiences with the treatment of non-small cell lung cancer (NSCLC) with cetuximab and compare the therapeutic effects of cetuximab applied in the first line and non-first line settings.

METHODSFrom October 1, 2006 to December 31, 2009, 16 NSCLC patients were treated with cetuximab combined with standard chemotherapy in Sun Yat-sen University Cancer Center. The short-term efficacy of the therapeutic protocols were analyzed.

RESULTSA total of 115 cycles of cetuximab treatment were administered in these patients with a median of 6 cycles (7.5 in the first line setting and 2 in non-first line setting). In the 10 patients with cetuximab treatment in the first line setting, the ORR was 40.0% (4/10), DCR was 80.0% (8/10), median TTP was 6.5 months (2-19), and median OS was 8.5 months (2-48); in the non-first line setting, these indices were 33.3% (2/6), 33.3% (2/6), 3.5 months (3-4) and 18 months (4-28), respectively. Both ORR and DCR were similar between the first and non-first line settings (P=0.790, P=0.062). Ten of the patients (62.5%) developed acne-like rash within 3 weeks, who had an ORR of 60% (6/10) and DCR of 90% (9/10); the ORR and DCR in patients without acne-like rash were both 10.4% (1/6), showing no significant difference in ORR (P=0.080) but a significant difference in DCR between the two groups (P=0.003). No treatment-associated death or cetuximab-associated discontinuation occurred. Altogether 11 patients (68.8%) developed acne-like rash, which occurred within 3 weeks in 10 cases. Seven patients showed side effects associated with the chemotherapy.

CONCLUSIONCetuximab combined with standard chemotherapy is a good option for Chinese patients with NSCLC and the current data support the application of cetuximab in the first line setting.

Adult ; Aged ; Antibodies, Monoclonal, Humanized ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cetuximab ; Female ; Humans ; Lung Neoplasms ; drug therapy ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo explore the relationship between KRAS gene status and efficacy of Cetuximab (C225) combined with chemotherapy on advanced colorectal cancer in Chinese patients, and to evaluate the safety of C225.

METHODSFrom May 2006 to March 2009, 81 patients with advanced colorectal cancer received Cetuximab combined with chemotherapy were enrolled in this study. The rate of KRAS mutation and the relationship of KRAS with response rate (RR), progression-free survivor (PFS), overall survival (OS) and adverse reaction of C225 were analyzed retrospectively.

RESULTSAll the 81 patients received C225 therapy, and the overall RR was 33.3%. The RR of initiate therapy was 57.1%; of the second line and over the third line therapy was 38.5% and 22.0% respectively. KRAS gene phenotype examination was performed in 44 patients whose tumor samples were available. KRAS mutation was found in 20 cases (45%). Out of 44 patients, 43 were evaluable for response. RR was 5% and 43.48% in KRAS mutation and wild KRAS patients respectively (P =0.002). The median PFS was 7.0 weeks and 18.6 weeks in mutational KRAS patients and wild KRAS patients, reaching statistical significance (P =0.003). The median OS was 15.2 months and 17.3 months in mutational KRAS patients and wild KRAS patients respectively without statistical significance (P =0.463). The common adverse reactions were leucopenia, nausea, vomiting and rash. All the adverse reactions were tolerated. The incidence of skin rash in patients with mutational KRAS and patients without KRAS mutation was 40% and 42% respectively, without statistical significance (P =0.91).

CONCLUSIONC225 combined with chemotherapy is well-tolerated in Chinese patients with advanced colorectal cancer, and it can significantly prolong PFS of patients with wild KRAS as compared to patients with KRAS mutation.

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cetuximab ; Colorectal Neoplasms ; drug therapy ; genetics ; pathology ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins p21(ras) ; Retrospective Studies ; ras Proteins ; genetics