No abstract available.
Antibodies, Monoclonal, Humanized ; Humans ; Rectum* ; Cetuximab

Cetuximab, a chimeric mouse-human immunoglobulin, is an antiepidermal growth factor receptor monoclonal antibody. It has been approved by the U.S. Food and Drug Administration for the treatment of metastatic colorectal and head/neck cancer, but can cause fatal hypersensitivity reactions in some patients. A 66-year-old male with metastatic sigmoid cancer had cetuximab-induced anaphylaxis when the first dose of cetuximab was administered. Cetuximab was safely readministered for another 15 cycles based on the rapid desensitization protocol. We experienced a case of cetuximab-induced anaphylaxis on the first exposure which was successfully managed by rapid desensitization.
Aged ; Anaphylaxis* ; Desensitization, Immunologic ; Humans ; Hypersensitivity ; Immunoglobulins ; Male ; Sigmoid Neoplasms ; United States Food and Drug Administration ; Cetuximab

We report a case of paronychia induced by cetuximab in a 43-year-old woman. Cetuximab is an antibody to the epidermal growth factor receptor, and has previously been shown to block the proliferation of various cancer cells. The patient had taken cetuximab for the treatment of metastatic rectal cancer. One month after the injection of cetuximab, the patient visited our clinic with painful periungal edema and erythema. The lesions partially improved after treatment with systemic and topical antibiotics. But, after discontinuing cetuximab, there was a significant decrease in the erythematous and edematous plaques. Three weeks later, she was asymptomatic and the lesions had resolved completely.
Adult ; Anti-Bacterial Agents ; Edema ; Erythema ; Female ; Humans ; Paronychia* ; Receptor, Epidermal Growth Factor ; Rectal Neoplasms ; Cetuximab

PURPOSE: Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RAS Mutational analysis using a high-throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing. MATERIALS AND METHODS: Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status. RESULTS: The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88). CONCLUSION: Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.
Cetuximab* ; Colorectal Neoplasms* ; Disease-Free Survival ; Exons ; Genes, ras ; High-Throughput Nucleotide Sequencing ; Humans ; Salvage Therapy

OBJECTIVETo investigate the effect of FCGR3A polymorphisms on the antibody-dependent cell-mediated cytotoxicity (ADCC) activity induced by cetuximab against A549 cells.

METHODSA549 cell line was used as target cells and NKTm cells as effector cells. FCGR3A polymorphisms were detected by direct sequencing. The ADCC activity mediated by cetuximab was assessed by CCK-8 assay.

RESULTSThree genotypes of FCGR3A were detected:V/V,V/F,and F/F. The ADCC activity of NKTm cells with these three different genotypes mediated by cetuximab were significantly different (P=0.0015). NKTm cells with FCGR3A-158V/V genotypes had significantly higher ADCC activity than FCGR3A-V/F or F/F genotypes (P<0.01),whereas the ADCC activity between V/F and F/F genotype showed no statistical significance(P>0.05).

CONCLUSIONFCGR3A polymorphisms have an impact on ADCC activity mediated by cetuximab in NKTm cells.

Head and neck cancers comprise a heterogenous group of cancers that require a multidisciplinary approach. Surgery, radiation therapy, chemotherapy and, more recently, target therapy are often employed in various combinations in an attempt to eradicate both clinically apparent and occult disease. The role of chemotherapy in multimodality treatment for locally advanced head and neck squamous cell carcinoma, although firmly established, presents several unresolved issues. Concomitant platinum-based chemoradiation (CRT) is a standard treatment for unresectable, resectable but nonsurgically treated, and postoperative high-risk patients with locally advanced head and neck squamous cell carcinoma. Cetuximab administered concomitantly with radiotherapy has not been directly compared with CRT but offers a potential different approach using a noncytotoxic systemic agent. In recent years taxanes have been shown activity in head and neck cancers and are being incorporated into neo-adjuvant and concomitant chemotherapy regimens.
Carcinoma, Squamous Cell ; Chemoradiotherapy ; Drug Therapy* ; Head ; Head and Neck Neoplasms* ; Humans ; Neck ; Radiotherapy ; Taxoids ; Cetuximab

Targeted agents increase response rates and improved overall survival in treatment of metastatic gastrointestinal cancer. Therefore, physicians pay more attention to the role of targeted agents in treatment of local advanced gastrointestinal cancer. The clinical trials are ongoing to evaluate the efficacy of Trastuzumab in neoadjuvant treatment of local advanced gastric cancer with HER-2 gene over expression. Many studies reported Cetuximab plus chemotherapy as a conversion treatment improve R0 resection rates and prolonged overall survival of the patients with potentially resectable colorectal cancer liver metastasis with wild type KRAS gene status. A phase III( clinical trial is assessing the conversion efficacy of Bevacizumab in unresectable disease with KRAS gene mutation. Current evidence showed that neoadjuvant therapy of targeted agents did not prolong survival of patients with resectable liver metastasis. However, this is controversial. In neoadjuvant therapy of local advanced rectal cancer, Cetuximab did not improve the rates of pathological complete response in most of the phase II( trials. Furthermore, there are no phase III( trials to assess the role of Bevacizumab. Compared to chemotherapy alone for metastatic cancer, it is more important to evaluate the interaction and synergistic action of targeted agents, cytotoxic drugs, surgery and radiation, to make a scientific multidisciplinary model in comprehensive treatment of local advanced cancer.
Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; Bevacizumab ; Cetuximab ; Gastrointestinal Neoplasms ; drug therapy ; Humans ; Liver Neoplasms ; Molecular Targeted Therapy ; Neoadjuvant Therapy ; Trastuzumab

We report a case of acneiform skin eruption induced by cetuximab in a 58-year-old man. Cetuximab is a new anticancer agent, which acts as a selective epidermal growth factor receptor monoclonal antibody. Our patient had taken cetuximab for the treatment of metastatic rectal cancer and visited our clinic with multiple erythematous papules and pustules on the face, postauricular area and anterior chest. A skin biopsy from his forehead revealed destruction of the follicular structure and perifollicular inflammatory cellular infiltrations composed of neutrophils and lymphocytes.
Acneiform Eruptions* ; Biopsy ; Forehead ; Humans ; Lymphocytes ; Middle Aged ; Neutrophils ; Receptor, Epidermal Growth Factor ; Rectal Neoplasms ; Skin ; Thorax ; Cetuximab

PURPOSE: A colorectal carcinoma is the fourth most common malignancy in the world. Unfortunately, only approximately 20% of the liver metastases are resectable at the initial presentation. Neoadjuvant chemotherapy has been used for downsizing in unresectable disease. In addition, the use of newer biologic agents, such as cetuximab and bevacizumab, has much improved responses in patients with unresectable colorectal liver metastases. The aim of this study was to report on patients who had received a curative resection following neoadjuvant chemotherapy including a molecularly targeted agent for unresectable colorectal liver metastases. METHODS: Following the neoadjuvant chemotherapy using cetuximab plus FOLFIRI (irinotecan and infused fluorouracil plus leucovorin) or bevacizumab plus FOLFOX (oxaliplatin and infused fluorouracil plus leucovorin), 10 patients with initially unresectable colorectal liver metastases underwent a curative surgical resection between September 2005 and June 2007. RESULTS: One patient underwent a right lobectomy, three patients a segmentectomy and five a wedge resection with or without radiofrequency ablation. With a median postoperative follow-up of 14 months (range, 1 to 22 months), five recurrences (50%) occurred. The common toxic effects were grade 2/3 skin toxicity (60%), grade 4 hematologic toxicity (20%), grade 3 gastrointestinal toxicity (10%), and grade 3 neurologic toxicity (10%). CONCLUSIONS: Our preliminary data suggests that neoadjuvant chemotherapy including a molecularly targeted agent may improve resectability in patients with initially unresectable colorectal liver metastases although a high recurrence rate exists. Randomized prospective studies comparing neoadjuvant chemotherapy including a targeted agent in cases of unresectable colorectal liver metastases are warranted.
Antibodies, Monoclonal, Humanized ; Bevacizumab ; Cetuximab ; Colorectal Neoplasms ; Fluorouracil ; Follow-Up Studies ; Humans ; Liver ; Mastectomy, Segmental ; Neoplasm Metastasis ; Recurrence ; Skin

5-Fluorouracil (5-FU) has been the main chemotherapeutic agent for the treatment of colorectal cancer for four decades with modest efficacy. Modulation of 5-FU by leucovorin or continuous infusion improves the response rate, but overall survival duration remains approximately 12 months. Many oral fluoropyrimidines have been studied, including capecitabine, UFT, S-1, and Eniluracil. Capecitabine has demonstrated equivalent efficacy with 5-FU and has been approved as first line treatment. CPT-11 demonstrated non-crossover resistance with 5-FU and was proven to be effective treatment for patients who received prior 5-FU. CPT-11 in combination with 5-FU has demonstrated improved response rate and overall survival duration over 5-FU or CPT-11. Oxaliplatin plus 5-FU has offered another effective treatment option for colorectal cancer. Both 5-FU plus leucovorin in combination with CPT-11 or oxaliplatin are widely used first-line chemotherapies for advanced colorectal cancer. The combinations of capecitabine with CPT-11 or oxaliplatin are being developed. Several molecular targeting agents such as EGFR inhibitors and antiangiogenic agents have developed. Cetuximab induces a broad range of cellular responses in tumors expressing EGFR, enhancing sensitivity to radiotherapy and chemotherapeutic agents. A key angiogenic pathway in the stimulation of tumour growth is the vascular endothelial growth factor (VEGF) pathway, inhibited by the monoclonal antibody bevacizumab. Phase II first line and phase III second line studies of oxaliplatin in combination with bevacizumab are now in progress. Optimal combinations and sequences of treatment are being studied, since several effective regimens have become available.
Angiogenesis Inhibitors ; Colorectal Neoplasms* ; Drug Therapy* ; Fluorouracil ; Humans ; Leucovorin ; Radiotherapy ; Vascular Endothelial Growth Factor A ; Bevacizumab ; Capecitabine ; Cetuximab