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

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

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

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

PURPOSE: Many reports about efficacy of cetuximab in the prolongation of survival have been published. Especially, the combination of cetuximab and FOLFIRI has a high activity even in prior irinotecan refractory metastatic colorectal cancer (mCRC). Beside small number of patients, we are trying to evaluate the efficacy and safety of cetuximab combined with FOLFIRI for patients who prior irinotecan chemotherapy had failed. METHODS: A retrospective analysis of 26 patients treated with cetuximab with FOLFIRI from July 2006 to August 2007 was done. All patients had already been treated with FOLFIRI chemotherapy in 1st line or 2nd line regimens for mCRC. The initial dose of cetuximab was 400 mg/m2 at the 1st week, after which the dose was 250 mg/m2 weekly plus FOLFIRI biweekly. We defined 1 cycle as 8 weeks, and the responses were evaluated at week 8. RESULTS: The median follow-up period was 6.2 (1.1~13.9) months. After 8 weeks, 50% of the patients had a partial response, and the disease control rate was 57.5%. The median time to progression was 3 months. EGFR expression and tumor response had no correlation (P=0.07). Skin reaction and tumor response (median time to progression) had a significant correlation (P= 0.022). Cetuximab did not increase the toxicity associated with FOLFIRI, except for an acneiform rash. CONCLUSIONS: Cetuximab combined with FOLFIRI chemotherapy was effective in treating mCRC patients after FOLFIRI regimen chemotherapy.
Antibodies, Monoclonal, Humanized ; Camptothecin ; Cetuximab ; Colorectal Neoplasms ; Exanthema ; Follow-Up Studies ; Humans ; Morpholines ; Oxazolidinones ; Retrospective Studies ; 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

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

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