FDA Approves Cetuximab for Metastatic Head and Neck Cancer

Source: MedScape News Today The US Food and Drug Administration (FDA) has approved cetuximab (Erbitux, Bristol-Myers Squibb ) for use in combination with chemotherapy for the treatment of metastatic head and neck cancer. Data show that when combined with cisplatin-based chemotherapy, cetuximab improved overall survival, compared with chemotherapy alone. According to the researchers, this is the first time in 3 decades — since cisplatin was first used in head and neck cancer — that any regimen has improved on its success. The improved survival that was seen after cetuximab was added to the regimen (at a median of 2.7 months) is "therefore notable." Cetuximab was approved in the United States in 2004 for the treatment of epidermal growth-factor receptor–positive late-stage colon cancer in patients who no longer responded to chemotherapy. In 2006, it was approved for use in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. This latest approval expands on that to cover metastatic head and neck cancer. The ability of cetuximab "to extend the lives of patients with head and neck cancer is an important tool for oncologists, who often rely on a multitreatment approach for patients," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, in a statement." Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have [...]

2011-11-08T12:00:48-07:00November, 2011|Oral Cancer News|

Ethanol Promotes Chemically Induced Oral Cancer in Mice through Activation of the 5-Lipoxygenase Pathway of Arachidonic Acid Metabolism

Source: Cancer Prevention Research Abstract Alcohol drinking is a known risk factor for oral cancer in humans. However, previous animal studies on the promoting effect of ethanol on oral carcinogenesis were inconclusive. It is necessary to develop an animal model with which the molecular mechanism of ethanol-related oral carcinogenesis may be elucidated to develop effective prevention strategies. In this study, mice were first treated with 4-nitroquinoline-1-oxide (4NQO, 100 μg/mL in drinking water) for 8 weeks and then given water or ethanol (8%) as the sole drink for another 16 weeks. During the experiment, 8% ethanol was well tolerated by mice. The incidence of squamous cell carcinoma (SCC) increased from 20% (8/41) to 43% (17/40; P < 0.05). Expression of 5-lipoxygenase (5-Lox) and cyclooxygenase 2 (Cox-2) was increased in dysplasia and SCC of 4NQO-treated tongues and further enhanced by ethanol. Using this mouse model, we further showed that fewer cancers were induced in Alox5−/− mice, as were cell proliferation, inflammation, and angiogenesis in the tongue, as compared with Alox5+/+ mice. Interestingly, Cox-2 expression was induced by ethanol in knockout mice, whereas 5-Lox and leukotriene A4 hydrolase (LTA4H) expression and leukotriene B4 (LTB4) biosynthesis were dramatically reduced. Moreover, ethanol enhanced expression and nuclear localization of 5-Lox and stimulated LTB4 biosynthesis in human tongue SCC cells (SCC-15 and SCC-4) in vitro. In conclusion, this study clearly showed that ethanol promoted 4NQO-induced oral carcinogenesis, at least in part, through further activation of the 5-Lox pathway of arachidonic acid metabolism. This news story was resourced [...]

Resveratrol Selectively Induces DNA Damage, Independent of Smad4 Expression, in Its Efficacy against Human Head & Neck Squamous Cell Carcinoma

Source: Clinical Cancer Research Author: Robert A. Sclafani, University of Colorado School of Medicine, Campus Box 8101, Room 9100, Aurora, CO 80045. Phone: 303-724-3271; Fax: 303-724-3215; E-mail:[email protected]   Abstract Purpose: Alterations in Smad4 signaling and its loss cause genomic instability and head and neck squamous cell carcinoma (HNSCC), suggesting that agents that target both Smad4-dependent and -independent pathways could control HNSCC. Experimental Design: Resveratrol efficacy was evaluated against the HNSCC cells FaDu, Cal27, Det562, and Cal27-Smad4 for viability, DNA damage, cell-cycle progression, and apoptosis, as well as γ-H2AX expression, and focus formation (γ-H2AX and Brca1). Resveratrol efficacy was also examined in nude mice for FaDu xenograft growth. Xenografts were analyzed for γ-H2AX and cleaved caspase-3. Results: Resveratrol (5–50 μmol/L) suppressed viability and induced DNA damage in FaDu and Cal27 cells but not in normal human epidermal keratinocytes and human foreskin fibroblasts, showing its selectivity toward HNSCC cells; however, Det562 cells were resistant to resveratrol even at 100 μmol/L. Cal27 cells stably transfected withSmad4 showed similar resveratrol effects as parental Cal27, indicating that a lack of resveratrol effect in Det562 cells was independent of Smad4 status in these cells. Furthermore, resveratrol caused S-phase arrest and apoptotic death of FaDu and Cal27 cells together with induction of Brca1 and γ-H2AX foci. Resveratrol (50 mg/kg body weight) treatment also inhibited FaDu tumor growth in nude mice, and γ-H2AX and cleaved caspase-3 were strongly increased in xenografts from resveratrol-treated mice compared with controls. Conclusion: Our findings for the first time showed antiproliferative, DNA damaging, and apoptotic effects of resveratrol in [...]

2011-08-15T10:20:48-07:00August, 2011|Oral Cancer News|

New Study on Tonsillar Squamous Cell Carcinoma

Source: SAGE Journals Online Objective. To analyze outcomes in patients with squamous cell carcinoma (SCCA) of the tonsil from the years 1998 to 2006. To assess factors that may affect disease-specific survival, such as patient characteristics and/or treatment modality. Study Design and Setting. National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program. Subjects and Methods. The SEER database was used to perform a population-based cohort analysis for patients diagnosed with SCCA of the tonsil from 1998 to 2006. Disease-specific survival was correlated with sex, age, ethnicity, year of diagnosis, and treatment modality in a univariate Cox proportional hazards analysis and a multiple Cox-regression model with and without interaction effect. Results. Applied inclusion criteria resulted in 8378 patients. Of this patient cohort, 80% were male and 85% were white. The mean patient age at diagnosis was 58.1 years. On univariate and multivariate analyses, ethnicities other than white carried a significantly higher rate of disease-specific death (hazard ratio = 1.71, P

New Strategies used to Identify Changes in Head and Neck Cancers

Source: GenomeWeb Daily News By Andrea Anderson CHICAGO– Researchers are making progress using high-throughput strategies to find previously unappreciated genetic and epigenetic quirks in head and neck cancer — including changes that may prove useful for diagnosing and tracking disease. Johns Hopkins University head and neck cancer research director David Sidransky described some of the work during an education session on molecular biology, targets, and pathways involved in head and neck cancer at the American Society of Clinical Oncology annual meeting here yesterday. Speaking during the same session, JHU oncologist Christine Chung and the University of Chicago's Ezra Cohen touched on strategies for targeting the types of mutations previously reported in head and neck cancer and the rationale behind targeted therapeutics already being tested or considered for the disease, respectively. Past studies have uncovered muted DNA methylation across the genomes of several cancer types, Sidransky explained, though methylation is also bumped up at specific sites in certain tumor types. Consequently, he said, researchers are using strategies such as real-time quantitative methylation-specific PCR (real-time QMSP) to look at methylation shifts in head and neck squamous cell carcinoma. In particular, he described work comparing methylation patterns in saliva and serum samples from individuals with HNSCC to those in samples from more than 800 apparently healthy individuals who are considered 'at-risk' of the disease because of smoking status and other exposures. At least two genes — KIF1A and EDNRB — seem to be more highly methylated in samples from those with HNSCC than [...]

Two Elements Predict Swallowing Difficulties after Radiotherapy

Source: International Medicine News LONDON – Nonglottic cancer and the presence of dysphagia before treatment are highly predictive for severe acute and late swallowing difficulties after radiotherapy for head and neck cancer, according to new data from the DAHANCA 6&7 randomized trial. Patients with nonglottic cancer were more likely than those with other cancer types to experience severe dysphagia at both 6 and 12 months. Dysphagia before treatment was also associated with both acute and late severe swallowing difficulties. "The peak incidence of dysphagia is seen during the first 6 months after radiotherapy," Hanna Rahbek Mortensen, Ph.D., reported in an analysis of the DAHANCA (Danish Head and Neck Cancer Group) 6&7 trial findings at the European Society for Therapeutic Radiation Oncology Anniversary Congress. "After 1 year, however, there is no further increase in severity or prevalence," said Dr. Mortensen of the department of experimental clinical oncology at Åarhus (Denmark) University Hospital. The trial involved 1,478 patients with squamous cell carcinomas of the glottic larynx, supraglottic larynx, pharynx, or oral cavity who were who were treated with five or six weekly fractions of radiotherapy in 1992-1999. The total dose of radiotherapy delivered was 66-68 Gy in 33-34 fractions. Efficacy data from the trial have already been published; they showed improved disease-specific but not overall survival of five vs. six fractions of radiotherapy (Lancet 2003;362:933-40). The aim of the present analysis was to use prospectively collected data from the trial to determine whether any factors could be used to establish which patients [...]

Oral Cancer…what does sex have to do with it?

Source: DentistryIQ.com The answer is … plenty! This issue will focus on oral cancer awareness. While there are many topics we can delve into regarding this dreadful disease, we will focus on a few topics. We will share two personal and very poignant stories. Kim Anzalotti, Bill Wislon, and Eva Grayzel impart information that will move you and make you think about your daily in-office procedures. JoAnn Gurenlian, RDH, PhD, will share insights on the human papillomavirus, or HPV, a sexually transmitted virus, and its relationship to oral cancer. And last, but certainly not least, Jamie O'Day, Treatment Facilities Coordinator, The Oral Cancer Foundation Inc., The Bruce Paltrow Oral Cancer Fund, will share her insight on oral cancer screening and the need for a thorough examination. One personal story is shared by Eva Grazel, an international motivational speaker, author, performer, and cancer survivor. I had the pleasure of meeting Eva a number of years ago. In 1998 at age 33, Eva, a non-smoker, saw a number of dentists and physicians for over two years for an “ulcer” on her tongue that became larger and more painful, without any resolution. She was finally diagnosed with advanced oral cancer, Stage IV squamous cell carcinoma, on the lateral border of her tongue. After the many missed opportunities for diagnosis, Eva was given a 15% chance of survival. While her late stage diagnosis is not uncommon, her recovery was unique, as she beat the odds. After diagnosis, Eva underwent a partial tongue reconstruction, a [...]

HPV is now the leading cause of oral cancer in the US: learn the facts.

Source: New York Daily News HPV, otherwise known as the human papillomavirus, is a leading cause of cervical cancer for women but the nasty virus is now causing a spike in oral cancer and ravaging an entirely different group: men. Cases of oral cancer resulting from exposure to the HPV-16 strain of the virus are hitting epidemic proportions in the U.S., doctors say. Though the mention of oral cancer evokes images of gravely-voiced chain-smokers, the disease now has a new face: mostly white, male, non-smokers in their late 30s and early 40s. The tumors forming on the back of their tongues and tonsils have nothing to do with nicotine – they are directly linked to engaging in oral sex with multiple female partners. "If you've had more than five or six sexual partners, you are at a higher risk," Dr. Eric M. Genden, professor and chair of head and neck surgery at Mount Sinai Medical center told the Daily News. "We're only now beginning to see the beginning of a bell curve." Women can get it from men as well although their chances are lower, according to doctors. The human papillomavirus (HPV), a nasty bug with strains that causes genital warts and cervical cancer in women, is now the top cause of oral cancer in men, beating out smoking and drinking, according to reports from the New England Journal of Medicine and the Journal of Oncology as well as other research and treating institutions. The number of smokers in the [...]

Tonsillar squamous cell carcinoma- are we making a difference?

Source: SAGE Journals Online Objective. To analyze outcomes in patients with squamous cell carcinoma (SCCA) of the tonsil from the years 1998 to 2006. To assess factors that may affect disease-specific survival, such as patient characteristics and/or treatment modality. Study Design and Setting. National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program. Subjects and Methods. The SEER database was used to perform a population-based cohort analysis for patients diagnosed with SCCA of the tonsil from 1998 to 2006. Disease-specific survival was correlated with sex, age, ethnicity, year of diagnosis, and treatment modality in a univariate Cox proportional hazards analysis and a multiple Cox-regression model with and without interaction effect. Results. Applied inclusion criteria resulted in 8378 patients. Of this patient cohort, 80% were male and 85% were white. The mean patient age at diagnosis was 58.1 years. On univariate and multivariate analyses, ethnicities other than white carried a significantly higher rate of disease-specific death (hazard ratio = 1.71, P < .001). Each additional year of age at the time of diagnosis carried approximately a 4% increase in likelihood of disease-specific death. With each passing year of time at diagnosis, patients carried a decreased risk of disease-specific death (P < .001); this value was significant in all 3 statistical models. Patients who underwent external-beam radiation had a higher likelihood of disease-specific survival with each passing year at time of diagnosis. Conclusion. Population analysis based on the SEER database reveals increased disease-specific survival from tonsillar SCCA in more recent years. This [...]

Expand the search for oral cancer

Dentistry's responsibilities remain vital in stopping cancer deaths By: Donna Grzegorek, RDH Source: RDH magazine As dental professionals, we have a remarkable opportunity to affect the health and well-being of each patient we treat. This responsibility manifests itself in patients' expectations, which is to inform them of disease at the earliest possible moment. This is the fifth consecutive year in which there has been an increase in the rate of occurrence of oral cancers; yet, for several decades the mortality rates for this insidious disease remained virtually unchanged. OCF As dental professionals and health-care providers, we have an obligation to be vigilant in our commitment to early detection, raising awareness, and the management of the cancer for which we as a profession are held accountable. Approximately 37,000 Americans will be diagnosed with oral or pharyngeal cancer this year. This menacing disease will cause 8,000 deaths, killing approximately one person per hour, 24 hours a day. Of these 37,000 newly-diagnosed individuals, only slightly more than half will survive five years. The mortality rate for oral cancer is higher than that of other cancers we hear about routinely such as cervical cancer, Hodgkin's lymphoma, laryngeal cancer, cancer of the testes, and endocrine system cancers such as thyroid or skin cancer (malignant melanoma). If you expand the definition of oral cancers to include cancer of the larynx, for which the risk factors are indistinguishable, the number of diagnosed cases grows to approximately 50,000 individuals and 13,500 deaths per year in the United States [...]

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