cetuximab

Hypersensitivity Reactions to Erbitux Caused by Tick Bites.

Source: Gastroenterology & Endoscopy News Hypersensitivity reactions to cetuximab (Erbitux, ImClone Systems/Bristol-Myers Squibb), a monoclonal antibody approved for use in colorectal cancer, are not caused by the drug itself but by preexisting immunoglobulin E (IgE) antibodies that may result from tick bites, researchers have found. Cetuximab, like other monoclonal antibodies, is generally associated with a low rate of severe anaphylactic reactions (3%), but reports of such reactions to cetuximab have recently increased in southeastern states, including Tennessee and North Carolina. Researchers found IgE antibodies in pretreatment samples of 68% of patients allergic to cetuximab that were specific for galactose-α-1,3-galactose, an oligosaccharide present on the Fab portion of the cetuximab heavy chain. The authors noted that rates of anaphylactic reaction may be lower with other monoclonal antibodies because cetuximab is produced in the mouse cell line SP2/0, which expresses this oligosaccharide, whereas most other monoclonal antibodies are produced in a Chinese hamster ovary cell line that does not express this molecule. Theories to explain the increased hypersensitivity of patients in the Southeast initially centered on exposure to worms, such as roundworms or tapeworms. However, researchers now believe the true culprit may be ticks, whose bites have resulted in the development of this type of IgE antibody. Pretreatment samples were obtained from 76 people treated with cetuximab at centers mainly in Tennessee, Arkansas and North Carolina; the control group included 72 people in Tennessee, 49 patients with cancer in northern California and 341 women in Boston. Of the patients on cetuximab, 25 [...]

Oral Cancer Foundation News Team - A2011-07-01T12:42:28-07:00July, 2011|Oral Cancer News|

Yale School of Medicine Researchers take a closer look at “smart drugs”

Source: Yale University Some of the most effective and expensive cancer drugs, dubbed "smart drugs" for their ability to stop tumors by targeting key drivers of cancer cell growth, are not effective in some patients. In two related studies, Yale School of Medicine researchers examined one such driver, the EGF receptor (EGFR), and found that a decoy receptor might be limiting the amount of drug that gets to the intended target. "We know that smart drugs like Cetuximab are not always effective in the cancer cells they're supposed to target because there are no positive predictive markers for selecting the patients who will benefit from treatment with EGFR-targeted therapies, including EGFR itself," said lead author Nita Maihle, professor in the Departments of Obstetrics, Gynecology & Reproductive Sciences and of Pathology at Yale School of Medicine. "Why would a patient be given an expensive drug if it doesn't work? Our studies provide new insight into this paradoxical EGFR testing conundrum." In a study published recently in the journal Cancer, Maihle and her team isolated a protein from human blood that looks like EGFR, but is actually a closely related variant called serum sEGFR. They showed that Cetuximab binds equally as well to serum sEGFR as it does to the intended EGFR cancer target. Those study results showed that sEGFR might act as a decoy receptor in the blood of cancer patients, tying up Cetuximab and therefore limiting the amount of Cetuximab that actually gets to the intended target. Such limitations may, [...]

Oral Cancer Foundation News Team - A2011-05-19T13:43:34-07:00May, 2011|Oral Cancer News|

HPV and EGFR are hottest topics in head and neck cancer

Source: www.medscape.com Author: Zosia Chustecka The hottest topic in head and neck cancers is the role of human papillomavirus (HPV) in the disease, although there is also a lot interest in treatment with EGRF inhibitors, especially the second-generation products, according to an expert here at the European Society for Therapeutic Radiology and Oncology 11th Biennial Conference. HPV has only been associated with head and neck cancer in the last few years, but it is now clear that patients who are positive for the virus have a better prognosis, said Cai Grau, MD, DMSC, professor of oncology at Aarhus University Hospital, Denmark. He chaired a session during which both hot topics were discussed. "These patients have a better prognosis, irrespective of treatment, and their risk of a second cancer is virtually zero," added session participant Lisa Licitra, MD, medical oncologist at the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan, Italy. However, there is a difference between patients in the United States and those in Europe with regard to risk, she told meeting attendees. For American patterns, Dr. Licitra cited the analysis published last year in the New England Journal of Medicine (2010;363:24-35), which reported a risk model for death from oropharyngeal squamous cell carcinoma on the basis of HPV status, pack-years of tobacco smoking, and tumor and nodal stage. In this 266-patient cohort, 43% were low risk, 30% were intermediate risk, and 27% were high risk. Dr. Licitra reported that when she performed the same analysis [...]

Oral Cancer Foundation News Team - A2011-05-17T06:56:01-07:00May, 2011|Oral Cancer News|

Cetuximab therapy for head and neck squamous cell carcinoma: a systematic review of the data

Source: http://oto.sagepub.com/ Authors: Travis D. Reeves, MD et al. Objective: To review the current state of the data on the use of cetuximab in head and neck squamous cell carcinoma (HNSCC). Data Sources: The National Center for Biotechnology Information’s PubMed and the Cochrane collection. Review Methods. Search terms included cetuximab and head and neck cancer. These results were reviewed, and a second search was performed using limits: meta-analysis, randomized controlled trial, and clinical trial. Results: The literature search yielded 412 articles. Fifteen were identified for analysis. For patients with recurrent/metastatic disease who received combination chemotherapy in phase I/II trials, the overall response (OR) was 18.7% (95% confidence interval [CI], 10.4%-27.0%). Phase III trial data for combination chemotherapy in recurrent/metastatic disease showed OR to be 17.0% (95% CI, 12.6%-21.4%) for platinum-based regimens and 34.2% (28.6%-39.7%) for platinum-based regimens with cetuximab. For this same group, the estimated aggregate hazard ratio comparing platinum-based therapy plus cetuximab to platinum therapy alone was 1.10 (95% CI, 0.78-1.54), indicating no significant improvement in overall survival in the aggregate analysis. Combination chemoradiation with cetuximab in both phase I/II trials and the single phase III trial shows enhanced responsiveness, but the data are difficult to interpret because it is not used with standard-of-care regimens for advanced-stage disease. Conclusion: Early evidence has shown cetuximab to be effective in the treatment of HNSCC, and it should be used to enhance, but not replace, current treatment paradigms until further phase III data are available. Note: This article was presented at the [...]

Oral Cancer Foundation News Team - A2011-03-05T12:32:58-07:00March, 2011|Oral Cancer News|

Rash prediction in lung cancer?

Source: www.medscape.com Author: Maurie Markman, MD Hello. I am Dr. Maurie Markman from Cancer Treatment Centers of America in Philadelphia. I wanted to briefly discuss with you a very interesting paper[1] that appeared online in The Lancet Oncology on December 20th, 2010, and will be in print soon. The paper was entitled "First-Cycle Rash and Survival in Patients With Advanced Non-Small-Cell Lung Cancer Receiving Cetuximab in Combination With First-Line Chemotherapy: A Subgroup Analysis of Data From the FLEX Phase 3 Study." This was a very interesting subgroup analysis -- a retrospective analysis. What the group of investigators attempted to look at was the impact on a patient who received cetuximab and developed a rash compared with individuals who received cetuximab and did not develop a rash. And, of course, the other control group here would be the patients who received chemotherapy without cetuximab. What this retrospective analysis demonstrated was that overall survival in patients who received combination chemotherapy plus cetuximab and who developed a rash was significantly longer in all of the subtypes of non-small cell lung cancer that were looked at (including squamous and adenocarcinoma), compared with chemotherapy alone or chemotherapy plus cetuximab and no development of a rash. These data, which are quite provocative and need to be confirmed by others, suggest that the development of a rash may be a reasonable clinical biomarker of the potential impact of this targeted agent on cancer. That is, the development of a rash suggests that there is going to be [...]

Oral Cancer Foundation News Team - A2011-01-26T08:09:24-07:00January, 2011|Oral Cancer News|

ASCO: Non-platinum regimen works in head, neck cancer

Source: www.medpagetoday.com Author: Michael Smith, North American Correspondent, MedPage Today A novel non-platinum-based regimen was efficacious in recurrent or metastatic squamous cell head and neck cancer, researchers said. The combination of pemetrexed (Alimta) and bevacizumab (Avastin) yielded a response rate of 30% in a small single-arm trial, according to Athanassios Argiris, MD, of the University of Pittsburgh, and colleagues. The combination also increased the length of time before patients progressed, and increased median overall survival, Argiris and colleagues reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology here. Patients with recurrent or metastatic disease typically have a poor prognosis, the researchers said, with median survival between six and nine months with standard chemotherapy. But, in other research, adding the monoclonal antibody cetuximab (Erbitux) to platinum-based chemotherapy increased survival, they said. Bevacizumab is a monoclonal antibody that targets the vascular epithelial growth factor (VEGF), which is expressed in squamous cell head and neck cancer; high levels of VEGF correlate with poor outcome, they noted. The researchers hypothesized that the antibody might enhance the activity of pemetrexed, which is a multi-targeted antifolate indicated for malignant pleural mesothelioma and non-small cell lung cancer. To test the idea, they analyzed results of treating 37 patients given 500 mg/m2 of pemetrexed and 15 mg/kg of bevacizumab intravenously every 21 days until disease progression. Patients were also given folic acid and vitamin B12. The primary endpoint of the study was time to progression, they said, but the researchers [...]

Oral Cancer Foundation News Team - A2010-06-06T07:32:19-07:00June, 2010|Oral Cancer News|

Boehringer Ingelheim will announce preliminary data in the area of head and neck cancer

Source: pr-usa.net Author: press release Boehringer Ingelheim will announce preliminary data in the areas of head and neck cancer and non-small cell lung cancer (NSCLC) for one of the company's investigational compounds, BIBW 2992. These data will be presented at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. BIBW 2992 is an orally-administered small molecule under development that irreversibly inhibits the epidermal growth factor receptor (EGFR/HER1) and human epidermal receptor 2 (HER2) tyrosine kinases. BIBW 2992 data in head and neck cancer(1) New data will report preliminary best response analysis for 74/109 patients from an ongoing Phase 2 study of 124 patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN) who did not respond to platinum-containing therapy. In this study, patients were initially randomly assigned to either BIBW 2992 or cetuximab. Twenty-two percent of the 34 patients receiving BIBW 2992 experienced reduction in tumor size (measured as partial response), compared to 13 percent of the 40 patients receiving cetuximab. Preliminary safety analyses revealed diarrhea and skin-related adverse events as the most common adverse events associated with BIBW 2992. "Metastatic head and neck cancer has a very poor prognosis, and patients are in desperate need for new treatment options," says Tanguy Y. Seiwert, M.D., lead investigator of the trial, University of Chicago Medical Center. "These findings, while preliminary, are encouraging and warrant further investigation of BIBW 2992 in head and neck cancer."

Oral Cancer Foundation News Team - A2010-05-23T12:55:48-07:00May, 2010|Oral Cancer News|

Integration of epidermal growth factor receptor inhibitors with preoperative chemoradiation

Source: Clincancerres Author: Annelies Debucquoy1, Jean-Pascal Machiels2, William H. McBride3, and Karin Haustermans1 Corresponding Author: Annelies Debucquoy, Laboratory of Experimental Radiotherapy, Department of Radiation Oncology, CDG Building, Box 815, UH Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Phone: 32-16-346900; Fax: 32-16-346905; E-mail:[email protected]. Abstract In many different cancer cell types, the epidermal growth factor receptor (EGFR) pathway becomes hyperactivated because of overproduction of the ligand, overproduction of the receptor, or constitutive activation of the receptor. The overproduction of EGFR and its ligands correlates with poor prognosis in several solid tumors such as lung, colon, and ovary. These observations led to the development of EGFR inhibitors for anticancer treatment. In the last few years, promising results have been obtained in several tumor types, with EGFR inhibitors given as monotherapy or in combined treatments. In particular, cetuximab in combination with curative-intent radiotherapy in head and neck cancer increases median survival over radiation alone. Similarly, the same approach might benefit patients with locally advanced rectal cancer. Unfortunately, the first clinical studies combining chemoradiation with cetuximab in rectal cancer gave disappointing results. Translational research suggested that the low response rate observed might have been due to the strong antiproliferative effect of cetuximab that may have compromised the activity of chemotherapeutics that target proliferating cells. This result indicates the need for more translational research to unravel how the molecular mechanisms might be manipulated to optimize the combined treatment regimen and to identify biomarkers that can select those patients who will derive most benefit. Clin Cancer Res; 16(10); OF1–6. ©2010 AACR. [...]

Charlotte Parker2010-05-03T18:01:14-07:00May, 2010|Oral Cancer News|

Pitt researchers receive patent for new head and neck cancer treatment

Source: www.healthcanal.com Author: staff Researchers from the University of Pittsburgh School of Medicine have been awarded a patent from the U.S. Patent and Trademark Office for the development of a new DNA therapy for head and neck cancers. The therapy targets the epidermal growth factor receptor (EGFR), a protein found on the surface of many types of cancer cells that causes them to multiply. Standard treatments for head and neck cancers often are ineffective and tend to have debilitating side effects, explained Jennifer R. Grandis, M.D., professor of otolaryngology and pharmacology at Pitt and director of the Head and Neck Program at the University of Pittsburgh Cancer Institute (UPCI). “We set out to develop an alternative approach that is safe and effective for these cancers,” she said. The new treatment is based on a form of genetic therapy called “antisense,” or AS, in which a synthesized strand of DNA or RNA targets the EGFR genes within a head and neck tumor. The therapy blocks the production of a protein produced by the gene. According to Dr. Grandis, expectations were exceeded in a phase I study of the therapy that was designed primarily to determine the safety and potential toxicity of EGFR AS injections in patients with advanced head and neck cancers. “Not only were the AS injections well-tolerated, but tumors disappeared or shrank considerably in 29 percent of the patients,” said Dr. Grandis. “These results show that EGFR AS therapy has great potential as a safe, effective treatment.” A phase [...]

Oral Cancer Foundation News Team - A2010-01-31T06:34:56-07:00January, 2010|Oral Cancer News|

Idera obtains clinical milestone under collaboration with Merck

Source: www.tradingmarkets.com Author: staff Idera Pharmaceuticals, a biotechnology company, has achieved a milestone under its worldwide licensing and collaboration agreement with Merck KGaA, Darmstadt, Germany. The milestone was achieved upon initiation of a Phase II trial by Merck KGaA of EMD 1201081, a novel agonist of toll-like receptor 9 (TLR9), in combination with cetuximab in second-line cetuximab-naive patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Under the terms of the agreement, the company is entitled to receive a payment of E3 million from Merck KGaA during the first quarter of 2010. The clinical trial is being conducted in eight countries, including the US. Idera Pharmaceuticals entered into a worldwide licensing and collaboration agreement with Merck KGaA, Darmstadt, Germany in December 2007 for the research, development and commercialization of Idera's TLR9 agonists, including IMO-2055, for the potential treatment of certain cancers. In addition to the clinical study announced today, under the company's collaboration with Merck KGaA, EMD 1201081 is currently being evaluated in a Phase Ib clinical trial in combination with Tarceva and Avastin in patients with advanced non-small cell lung cancer and in a Phase Ib clinical trial in combination with Erbitux and an irinotecan-containing treatment regimen in patients with colorectal cancer. Alice Bexon, vice president of clinical development at Idera, said: "We are very pleased with Merck KGaA's initiation of this randomized Phase II clinical trial of EMD 1201081 in combination with cetuximab in patients with head and neck cancer. "Under our collaboration with [...]

Oral Cancer Foundation News Team - A2010-01-22T09:59:21-07:00January, 2010|Oral Cancer News|