10/7/2005 Oslo, Norway Robert Preidt Forbes.com Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) shows promise in preventing mouth cancer in former and current smokers but may pose a heart risk, according to a Norwegian study in this week's issue of The Lancet. The study of more than 900 active and former smokers concluded that use of NSAID painkillers like ibuprofen and naproxen -- but not aspirin -- reduced the risk of mouth cancer by half but also doubled users' risk of death from heart disease. The study authors said their results show the need for careful risk-benefit analysis when long-term NSAID use is being considered. The study did not include data on use of the cox-2 inhibitor subclass of NSAIDs, which includes Vioxx, Celebrex and Bextra. The findings were first reported last spring at the annual meeting of the American Association for Cancer Research. Researchers led by Dr. Jon Sudbo of Norwegian Radium Hospital, Oslo, found that NSAIDs reduced the risk of oral cancer by 53 percent, even in active smokers. This protective effect against oral cancer is comparable to quitting smoking. However, the study found this protective effect against oral cancer didn't translate into increased overall survival. That's because long-term NSAID use doubled the risk of death due to heart disease, the study found. The study authors noted that oral cancer prevention trials of NSAIDs are either planned or already under way. "Researchers of these trials must carefully monitor potential adverse cardiovascular effects in their populations, which are at [...]

10/6/2005 Ketchum, ID staff CancerConsultants.com According to a phase I clinical trial published in the Journal of Clinical Oncology, 22% of patients with recurrent or metastatic squamous cell cancer of the head and neck experienced a partial reduction of their cancer following treatment with Iressa® (gefitinib) and Celebrex® (celecoxib). Head and neck cancers originate in the throat, larynx (voice box), pharynx, salivary glands, or oral cavity (lip, mouth, tongue). Most head and neck cancers involve squamous cells, which are the cells that line the mouth, throat, and other structures. When initially diagnosed, more than 70% of patients have cancer that has advanced locally, regionally, or to distant locations in the body. Iressa is an anti-cancer agent that selectively blocks epidermal growth factor receptors (EGFR). EGFR is a protein involved in the growth and replication of a cell. In some cancers, the EGFR may not be working properly, leading to excessive replication of the cancer cell. Iressa is taken orally and binds to a portion of EGFR to inhibit cancer cell growth. Celebrex is a pain reliever that inhibits the COX-2 enzyme. COX-2 is overexpressed in squamous cell carcinoma of the head and neck, and higher levels are associated with worse prognosis. To evaluate use of Iressa and Celebrex in patients with recurrent or metastatic squamous cell carcinoma of the head and neck, researchers conducted a phase I clinical trial in 19 patients. All patients had inoperable cancer and had experienced cancer progression after at least one previous regimen of chemotherapy [...]

10/6/2005 Toronto, Ontario press release Newswire Canada (www.newswire.ca) Viventia Biotech Inc. today announced that it has received clearance from Health Canada to initiate a Phase II study evaluating Proxinium(TM) for the treatment of patients with chemotherapy-refractory recurrent head and neck cancer. "This clearance will allow us to expand our proposed Phase II trial for Proxinium(TM) to include Canadian patients and reflects our strategy to ultimately develop Proxinium(TM) on a global basis," said Dr. Nick Glover, Viventia's President and CEO. Viventia recently announced it had been cleared by the FDA to initiate a Phase II trial of Proxinium(TM) for chemotherapy-refractory recurrent head and neck cancer. The Company anticipates initiating the trial by the end of 2005. Information for physicians and patients will be made available on the Company's website, www.viventia.com. About Proxinium(TM) Proxinium(TM) combines a powerful cytotoxic protein payload with the highly precise tumour-targeting characteristics of a monoclonal antibody. A single molecule of the cytotoxic protein payload, Pseudomonas exotoxin, is capable of killing a cancer cell. The antibody fragment of Proxinium(TM) targets EpCAM -- an antigen that is highly expressed on many epithelial cancers including head & neck cancer, ensuring that the payload is delivered directly to the tumour. Proxinium(TM) has been designated an Orphan Drug for the treatment of head and neck cancer in the U.S. and EU. Head and neck cancer is the 9th most common cancer in North America, with approximately 55,000 new cases diagnosed annually in the U.S. alone, leading to 14,000 deaths annually. Head and neck [...]

10/6/2005 Philadelphia, PA press release Genetic Engineering News (www.genengnews.com) Zila Pharmaceuticals, Inc., a business unit of Zila, Inc. will launch its ViziLite(R) Plus with TBlue630(TM) oral lesion identification and marking system at the 146th American Dental Association Annual Session in Philadelphia, October 6 to 9, 2005. ViziLite(R) Plus combines the oral screening technology of ViziLite, an advanced chemiluminescent light technology to help detect oral abnormalities, with TBlue630, a marking system using Zila(R) Tolonium Chloride (ZTC(TM)), the only patented pharmaceutical-grade form of toluidine blue that has been cleared by the FDA for use in marking lesions identified during a ViziLite(R) examination. ViziLite(R) Plus makes oral screening more comprehensive than ever before and is indicated for use in individuals at increased risk of oral cancer: if ViziLite(R) reveals an abnormality, TBlue630 can then be used to mark suspicious lesions for further evaluation. Douglas D. Burkett, Ph.D., Zila's Chairman, President and CEO, stated, "The launch of ViziLite(R) Plus with TBlue630 is an important milestone in the fight against oral cancer. The use of Zila(R) Tolonium Chloride in this new system provides the practitioner with an opportunity to further evaluate and monitor lesions after they are identified during a ViziLite(R) examination. ViziLite(R) Plus helps dental professionals perform a complete and thorough oral screening, and we all recognize that better screening saves lives. We are pleased that with the recent addition of Sullivan-Schein Dental, all major dental distributors in the U.S. are now promoting ViziLite(R)." Zila Pharmaceuticals will supply ViziLite(R) Plus in product configurations of [...]

10/8/2005 Columbus, OH staff Science Daily (www.sciencedaily.com) New research shows that a small gene variation that increases the risk of inherited cancer can also arise during the development of spontaneous, or non-inherited, tumors. The findings, published in the Oct. 5 issue of the Journal of the American Medical Association, suggest that the variation might play a fundamental role in the development and spread of cancer in the body, and that the variant could be an important target for anticancer drugs. The research focused on the gene for type 1 transforming growth factor-beta receptor, or TGFBR1, and on a variation of that gene, TGFBR1-6A. The 6A variant can be inherited and can increase cancer susceptibility by 19 percent in individuals with one copy of the gene and by 70 percent in those carrying two copies. The study showed that the 6A variant, which is carried by nearly one in seven Americans generally and by one in six people with cancer, can also arise as a gene mutation during cancer development. The research was led by scientists at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University . “Our findings show for the first time that the 6A variation of this gene also arises by mutation during tumor development in patients born with the normal TGFBR1 gene, and that this mutation may contribute to tumor growth and spread,” says principal [...]

10/3/2005 Philadelphia, PA Maria M. LoTempio et al. Clinical Cancer Research Vol. 11, 6994-7002, October 1, 2005 Purpose: The purpose of this study was to determine whether curcumin would trigger cell death in the head and neck squamous cell carcinoma (HNSCC) cell lines CCL 23, CAL 27, and UM-SCC1 in a dose-dependent fashion. Experimental Design: HNSCC cells were treated with curcumin and assayed for in vitro growth suppression using 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide and fluorescence-activated cell sorting analyses. Expression of p16, cyclin D1, phospho-Iß, and nuclear factor-ß (NF-ß) were measured by Western blotting, gel shift, and immunofluorescence. Results: Addition of curcumin resulted in a dose-dependent growth inhibition of all three cell lines. Curcumin treatment resulted in reduced nuclear expression of NF-ß. This effect on NF-ß was further reflected in the decreased expression of phospho-Iß-. Whereas the expression of cyclin D1, an NF-ß–activated protein, was also reduced, there was no difference in the expression of p16 at the initial times after curcumin treatment. In vivo growth studies were done using nude mice xenograft tumors. Curcumin was applied as a noninvasive topical paste to the tumors and inhibition of tumor growth was observed in xenografts from the CAL27 cell line. Conclusions: Curcumin treatment resulted in suppression of HNSCC growth both in vitro and in vivo. Our data support further investigation into the potential use for curcumin as an adjuvant or chemopreventive agent in head and neck cancer. Authors: Maria M. LoTempio1, Mysore S. Veena2, Helen L. Steele1, Bharathi Ramamurthy2, Tirunelveli S. Ramalingam1, Alen [...]

10/1/2005 Authors: See below Laryngoscope, October 1, 2005; 115(10): 1813-1817 OBJECTIVES/HYPOTHESIS: The detection of distant metastases during screening influences the choice of treatment in patients with head and neck squamous cell carcinoma. A previous study in the authors' institution showed that chest computed tomography (CT) scan was the most important screening technique. Different clinical risk factors in patients with head and neck squamous cell carcinoma for the development of distant metastases were identified. STUDY DESIGN:: Retrospective cohort study. METHODS: To evaluate the authors' diagnostic strategy, the accuracy of screening for distant metastases with chest CT in 109 consecutive patients with head and neck squamous cell carcinoma with risk factors between 1997 and 2000 was retrospectively analyzed. RESULTS: Preoperative screening with CT revealed 20 patients (18%) with lung metastases and 1 liver metastasis. Despite negative screening with chest CT, 9 (11%) patients developed distant metastases within 12 months during follow-up. Sensitivity of the chest CT was 73%; the specificity was 80%. CONCLUSION: Although chest CT frequently detects distant metastases, there seems to be a need for a more sensitive and whole-body screening technique. From the Departments of Otolaryngolog / Head and Neck Surgery (j.b., r.d.b., r.c.l.), Clinical Epidemiology and Biostatistics (o.h.s.), Nuclear Medicine and Positron Emission Tomography Research (o.h.s.), Radiology (r.p.g., j.a.c.), and Radiation Oncology (j.a.l.), VU University Medical Center, Amsterdam, The Netherlands. Authors: Jolijn Brouwer, Remco de Bree, Otto S Hoekstra, Richard P Golding, Johannes A Langendijk, Jonas A Castelijns, and C Rene Leemans

9/29/2005 Boston, MA staff CancerConsultants (professional.cancerconsultants.com) Researchers from Massachusetts General Hospital have reported that the dose of Taxol® (paclitaxel) given with hyperfractionated radiotherapy can be dose escalated in patients receiving Ethyol (amifostine). The details of this dose escalation trial were reported in the October 1, 2005, issue of Cancer . Combined radiation therapy and chemotherapy are standard treatments for patients with advanced head and neck cancers, but most patients have recurrent disease after treatment. Ethyol is a radiation protector and the only drug of this class that has been approved by the FDA for this use in patients receiving radiation therapy for cancers of the head and neck. Clinical trials have demonstrated that Ethyol can reduce both acute and late radiation-induced side effects. In the pivotal trial involving patients with head and neck cancer, Ethyol reduced the incidence of xerostomia but had no effect on the incidence or severity of oral mucositis. Ethyol has also been shown to reduce the incidence of grade 2-3 bladder and GI toxicities in patients receiving pelvic radiation therapy and more recently has been associated with decreased toxicities in patients receiving high-dose melphalan. The current study was a multi-institution phase I clinical trial that included 36 patients with advanced head and neck cancer. Patients were treated with radiation therapy plus weekly Taxol. The number of doses of Taxol was escalated from a minimum of three to a maximum of six. Twenty-eight of these patients received Ethyol; eight received no Ethyol. Patients not receiving Ethyol tolerated [...]

9/29/2005 Bethesda, MD Ann O'Mara Journal of Clinical Oncology, Vol 23, No 28 (October 1), 2005: pp. 6820-6821 Throughout the last decade, caring for a loved one with a cancer diagnosis has developed both in the sheer numbers of people providing the service and in the complexity of tasks required by cancer patients. Between 1997 and 2005, the number of Americans diagnosed with cancer has grown from 900,000 to 1.3 million, and the number of survivors has grown from 7.4 million to 9 million.1 With cancer care now routinely being delivered on an outpatient basis, informal caregivers' responsibilities have gone far beyond the tasks of transportation, shopping, household chores, and personal care. Administering oral and parenteral medications, performing wound care, and monitoring signs and symptoms are a few of the more demanding, yet routine tasks. The selection of an informal caregiver, like the diagnosis of cancer itself, is a random event, and there are no training programs to prepare individuals to be one. Thus, it comes as no surprise when we read of a new study, once again, highlighting the physical, emotional, and economic burdens that caregiving has placed on families and friends. What have these studies taught us throughout the years? Just as we have learned that cancer is not one disease, but a constellation of many, informal caregiving is not a simple occurrence, as the caring reflects the variability associated with the type and stage of disease, age of the patient, and the treatment modalities. However, these variables [...]

9/28/2005 Leicester, England D E Brenner and A J Gescher British Journal of Cancer (2005) 93, 735-739 The concept of delaying or preventing epithelial transformation remains a viable and attainable goal for the future. Drug-based strategies for chemoprevention of the future may predominantly rely upon targeted therapies with tolerable but defined toxicities for treatment of individuals diagnosed with intraepithelial neoplasias. Foods, diet manipulation strategies, or nutraceuticals may be more appropriate to delay or prevent carcinogenesis progression in healthy populations with genetic or epidemiologic evidence of risk for future transformation. Three recent publications have demonstrated an unacceptable therapeutic index due to cardiovascular toxicity of selective cyclooxygenase-2 inhibitors when used for cancer preventive or anti-inflammatory indications (Bresalier et al, 2005; Nussmeier et al, 2005; Solomon et al, 2005). These data have focused the debate on whether pharmacologic interventions aimed at delaying or preventing the transformation of organ epithelia should proceed. Further, bad news for proponents of the cancer chemoprevention approach emerged recently from a trial of -tocopherol supplements in patients with stage I or II head and neck cancer treated by radiation therapy (Bairati et al, 2005). In these patients, the incidence of second primary cancers was higher (hazard ratio: 2.88) than that in patients who received the placebo. The corollaries of these clinical results have been amply debated (for example, see Alberts et al, 2005; Drazen, 2005; Meyskens and Szabo, 2005). In this minireview, we wish to distill some crucial issues from that debate, and re-evaluate current and prospective chemoprevention strategies [...]