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

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

The last several years have major advances in chemotherapy treatment for adjuvant and metastatic colorectal cancer. We've come from an overall survival of 6 months in patients treated with best supportive care in the mid 1980s and even in the early 1990s. The use of 5-FU/leucovorin alone generates an overall survival of about 6 months. The addition of irinotecan/oxaliplatin allows patients to live a median of about 15 to 17 months. If we make use of all 3 active drugs, FOLFOX and FOLFIRI in a sequential manner, we'll be able to generate an overall survival of about 20 months. Recently, the addition of molecular therapy, in particular bevacizumab and cetuximab to these cytotoxic drugs has allowed us to break the brick wall that was placed at about 2 years median overall survival in large phase 3 trials in patients with metastatic colorectal cancer. The recent presentations provided further evidence that the standard of care in the treatment of advanced CRC consists of a combination of highly active cytotoxic chemotherapy plus the addition of a biologic agents, For clinical research, investigation of the best therapy for CRC has clearly shifted away from investigating conventional chemotherapy toward the question of how to make best use of all available active agents, particularly the novel biologics. Randomized trials have also shown that preoperative chemoradiation yields higher rates of pathologic complete response and local control, compared with radiotherapy alone. In this article, I review recent trials on preoperative and adjuvant therapy of localized rectal cancer. The roles of newer agents, such as capecitabine, oxaliplatin, and bevacizumab, are also discussed, and other key issues in the treatment of localized rectal cancer are reviewed. The planned phase 3 first-line trial will continue to elucidate the role of the currently available biologics in the treatment of CRC. In this article, the important advances in optimal chemotherapy of colorectal cancer will be summarized and approaches to multidisciplinary treatment decision-making in both adjuvant and metastatic settings will be reviewd.
Biological Factors ; Biological Products ; Colorectal Neoplasms* ; Drug Therapy* ; Humans ; Radiotherapy ; Rectal Neoplasms ; Standard of Care ; Bevacizumab ; Capecitabine ; Cetuximab

In Korea, the incidence of colorectal cancer has rapidly increased in both men and women during recent two decades, and now it is the third most common cancer. Deaths related to colorectal cancer has also rapidly increased. Currently, the fourth most common cause of cancer related death is that originated from colon cancer. Over the past several years, there was a significant improvement in survival of patients who suffered from colorectal cancer and it is partly due to the introduction of newer chemotherapeutic agents such as oxaliplatin, irinotecan, bevacizumab and cetuximab, and refined radiotherapy which can be delivered preoperatively or postoperatively. However, surgery still remains the only curative modality for early stage colorectal cancer and the principal one for locally advanced colorectal cancer. The goal in surgical treatment for colorectal cancer is to maximize not only the oncologic outcome through performing wide excision of the tumor bearing area and associated lymphatics with attention to the blood supply to that segment, but also to enhance the functional outcomes including preservation of bowel, anorectal and genitourinary function. The purpose of this article is to provide an overview of standard strategies in surgical management of colorectal cancer as well as a discussion of some of the important issues pertaining to the surgery.
Antibodies, Monoclonal, Humanized ; Bevacizumab ; Camptothecin ; Cetuximab ; Colonic Neoplasms ; Colorectal Neoplasms ; Female ; Humans ; Incidence ; Korea ; Male ; Organoplatinum Compounds ; Ursidae

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