Vandetanib Restores Head and Neck Squamous Cell Carcinoma Cells’ Sensitivity to Cisplatin and Radiation In Vivo and In Vitro

Abstract Purpose: We investigated whether vandetanib, an inhibitor of the tyrosine kinase activities of vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor (EGFR), and rearranged during transfection (RET), could augment the antitumor activity of radiation with or without cisplatin in preclinical in vitro and in vivo models of human head and neck squamous cell carcinoma (HNSCC). Experimental Design: OSC-19 and HN5 HNSCC cells that were cisplatin and radioresistant were treated with vandetanib, cisplatin, and radiation alone or in combination in vitro and in vivo using an orthotopic nude mouse model. Treatment effects were assessed using clonogenic survival assay, tumor volume, bioluminescence imaging, tumor growth delay, survival, microvessel density, tumor and endothelial cell apoptosis, and EGFR and Akt phosphorylation data. Results: Vandetanib plus cisplatin radiosensitized HNSCC cells in vitro and in vivo. The combination treatment with vandetanib, cisplatin, and radiation was superior to the rest of treatments (including the double combinations) in antitumoral effects, prolonging survival, decreasing cervical lymph node metastases in vivo. It also increased both tumor and tumor-associated endothelial cell apoptosis and decreased microvessel density in vivo. An analysis of tumor growth delay data revealed that vandetanib plus cisplatin enhanced radioresponse in vivo. All vandetanib-containing treatments inhibited EGFR and Akt phosphorylation in vitro and in vivo. Conclusion: The addition of vandetanib to combination therapy with cisplatin and radiation was able to effectively overcome cisplatin and radioresistance in in vitro and in vivo models of HNSCC. Further study of this regimen in clinical trials may be warranted. Clin [...]

2011-04-04T12:36:09-07:00April, 2011|Oral Cancer News|
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Three-drug combination shows long-lasting survival benefit in head and neck cancer patients

Source: www.medicalnewstoday.com Author: staff Adding a third drug (docetaxel) to a standard two-drug initial chemotherapy regimen significantly improves the long-term survival of patients with head and neck cancer, reducing the likelihood of dying by 26% over 6 years. The long-term results of the TAX 324 trial published Online First in The Lancet Oncology, confirm that this three-drug regimen should become the standard of care for patients who are suitable for induction therapy. Every year, cancers of the head and neck are diagnosed in more than 40 000 people in the USA. Standard treatment for these patients involves combining radiotherapy and chemotherapy with or without surgery, and the addition of induction chemotherapy has been shown to prolong survival. However, the best ways of combining these treatments remains unclear. In recent years, cisplatin plus fluorouracil (PF) has become a standard induction chemotherapy combination and has been shown to significantly prolong survival. The TAX 324 trial was designed to establish whether the addition of docetaxel to initial chemotherapy with cisplatin and fluorouracil (PF) might help patients with locally advanced head and neck cancer live longer. Between May 1999 and December 2003, 501 patients were recruited from 55 centres across the USA, Canada, Argentina, and Europe. In 2007, initial results (minimum follow-up 2 years) showed that induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) significantly improved survival compared with PF. To establish the durability of this survival benefit, Jochen Lorch from the Dana-Farber Cancer Institute, Boston, USA and colleagues evaluated the long-term follow-up of [...]

2011-01-13T17:08:13-07:00January, 2011|Oral Cancer News|
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Panitumumab Plus Platinum Chemo Misses Mark in Advanced Head and Neck Cancer

Source: Internal Medicine News Digital Network By: Patrice Wendling MILAN – Panitumumab plus chemotherapy with cisplatin and 5-fluorouracil proved clinically active, but failed to boost overall survival significantly in first-line recurrent or metastatic head and neck cancer in the global, phase III SPECTRUM trial. The primary end point of median overall survival showed a statistically insignificant increase from 9.0 months with chemotherapy alone to 11.1 months with the addition of panitumumab (Vectibix) (hazard ratio, 0.87; log-rank P = .14). Subgroup analysis revealed, however, that the effect of panitumumab, an anti–epidermal growth factor receptor (EGFR) monoclonal antibody, was not the same for all patients in the international study, lead author Dr. Jan Vermorken said at the annual congress of the European Society for Medical Oncology. Regional differences were observed, suggesting a greater benefit in patients from North/South America (HR, 0.69) and Western Europe (HR, 0.73) than in those in Eastern Europe (HR, 1.11). Asian Pacific patients fell somewhere in the middle (HR, 0.99). About 45% of patients in each arm used some form of subsequent antitumor activity once off the study protocol, but differences cropped up here as well. The use of cytotoxic chemotherapy was imbalanced at 30% in the panitumumab arm vs. 25% in the chemotherapy arm, while twice as many patients in the chemotherapy arm (12% vs. 6%) received subsequent targeted systemic therapy driven largely by the use of anti-EGFR monoclonal antibodies, observed Dr. Vermorken of the Antwerp University Hospital in Edegem, Belgium. “It’s clear this is the first [...]

2010-10-27T10:27:38-07:00October, 2010|Oral Cancer News|
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The Major Component In Tumeric Enhances The Effect Of Chemotherapy In Suppressing Head And Neck Cancers

Curcumin, the major component in the spice turmeric, when combined with the drug Cisplatin enhances the chemotherapy's suppression of head and neck cancer cell growth, researchers with UCLA's Jonsson Cancer Center have found. A naturally occurring spice widely used in South Asian and Middle Eastern cooking, Turmeric has long been known to have medicinal properties, attributed to its anti-inflammatory effects. Previous studies have shown it can suppress the growth of certain cancers, said Dr. Marilene Wang, a professor of head and neck surgery, lead author of the study and a Jonsson Cancer Center researcher. "Head and neck cancers, particularly cases diagnosed in a later stage, are terrible cancers that often require very radical surgeries and chemotherapy and radiation," Wang said. "They often don't present until late, and the structures in the head and neck are so vital that our treatments often cause disfigurement and severe loss of function. So using non-toxic curcumin as a treatment was a very appealing idea." The study, done in cells in Petri dishes and then in mouse models, appears in the October issue of the journal Molecular Cancer Therapeutics. In India, women for years have been using turmeric for medicinal purposes, as an anti-aging agent rubbed into their skin, to treat cramps during menstruation, as a poultice on the skin to promote wound healing and as an additive in cosmetics, said scientist Eri Srivatsan, an adjunct professor of surgery and a Jonsson Cancer Center researcher who, along with Wang, has been studying curcumin and its [...]

2010-10-21T15:06:19-07:00October, 2010|Oral Cancer News|
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Turmeric makes chemo more effective

Source: timesofindia.indiatimes.com Author: staff Researchers with UCLA's Jonsson Cancer Center have found that curcumin, the major component in the spice turmeric, when combined with the drug Cisplatin enhances the chemotherapy's suppression of head and neck cancer cell growth. In India, women for years have been using turmeric for medicinal purposes, as an anti-aging agent rubbed into their skin, to treat cramps during menstruation, as a poultice on the skin to promote wound healing and as an additive in cosmetics, said scientist Eri Srivatsan, an adjunct professor of surgery and a Jonsson Cancer Center researcher. Srivatsan, along with Dr. Marilene Wang, a professor of head and neck surgery, lead author of the study and a Jonsson Cancer Center researcher, has been studying curcumin and its anti-cancer properties for six years. A 2005 study by Wang and Srivatsan first showed that curcumin suppressed the growth of head and neck cancer cells, first in cells and then in mouse models. In the animal studies, the curcumin was applied directly onto the tumours in paste form because it did not dissolve in saline, which would have allowed it to be injected. In need of a better way to deliver the curcumin, the team collaborated with Dr. Kapil Mehta of M.D. Anderson Cancer Center and found that encapsulating the curcumin in a liposome, an artificially prepared vehicle that enclosed the spice component within its membrane, made the treatment injectable. The curcumin was injected into the tail vein of a mouse, where it circulated into the [...]

2010-10-20T08:54:24-07:00October, 2010|Oral Cancer News|
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Lilly presents new data in head and neck cancer – a difficult to treat cancer with poor survival rates

Source: www.prnewswire.com Author: press release Eli Lilly and Company announced today that its global Phase III trial evaluating Alimta® (pemetrexed for injection) in combination with cisplatin in patients with recurrent or metastatic squamous cell cancer of the head and neck (SCCHN) did not meet its primary endpoint for overall survival. Data were presented for the first time today at the 35th Annual Meeting of the European Society for Medical Oncology (ESMO). The Phase III study, the largest trial conducted in SCCHN to date, evaluated Alimta in combination with cisplatin compared with placebo plus cisplatin given every three weeks in a total of 795 patients. The primary objective of the study was to determine overall survival. Patient quality of life was also assessed, in addition to several pre-planned sub-group analyses. The Alimta/cisplatin regimen showed a median overall survival of 7.3 months compared with 6.3 months with cisplatin alone, a result not considered a statistically significant improvement (p=0.082). There was no significant difference in the quality of life scores for patients treated with either ALIMTA/cisplatin or cisplatin alone (p=0.200). As a result, Lilly will not be submitting marketing authorization applications for Alimta in SCCHN with either the U.S. Food and Drug Administration (FDA) or the European Medicine Agency (EMA). "The fact that combination treatment with pemetrexed and cisplatin did not improve overall survival in this study is disappointing, although perhaps not surprising given how difficult it can be to effectively treat metastatic or locally advanced head and neck cancer," said the study's [...]

2010-10-13T14:39:16-07:00October, 2010|Oral Cancer News|
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Organ preservation for advanced resectable cancer of the base of tongue and hypopharynx: a Southwest Oncology Group trial

Source: J Clin Oncol 23:88-95 Author: Susan G. Urba et al. Purpose: The Southwest Oncology Group designed a phase II trial for patients with base of tongue or hypopharyngeal cancer to evaluate the complete histologic response rate at the primary site after induction chemotherapy followed by chemoradiotherapy for responders. Secondary end points were the rate of organ preservation and the need for salvage surgery. Patients and Methods: Fifty-nine eligible patients were enrolled; 37 had base of tongue cancer, and 22 had hypopharynx cancer. Forty-two percent had stage III disease, and 58% had stage IV disease. Induction chemotherapy was two cycles of cisplatin 100 mg/m2 and fluorouracil 1,000 mg/m2/d for 5 days. Patients who had a greater than 50% response at the primary site were treated with radiation 72Gy and concurrent cisplatin 100 mg/m2 for three cycles. Patients with less than partial response at the primary had immediate salvage surgery. Results: Forty-five patients (76%) had a greater than 50% response at the primary after induction chemotherapy; 43 went on to receive definitive chemoradiotherapy. Thirty-two patients (54%) achieved a histologic complete response at the primary site, and an additional nine patients had a complete clinical response, but biopsy was not done. Seventy-five percent of patients did not require surgery at the primary tumor site. The 3-year overall survival was 64%. The 3-year progression-free survival with organ preservation was 52%. Conclusion: Patients with base of tongue or hypopharyngeal cancer treated with this regimen of induction chemotherapy followed by definitive chemoradiotherapy have a good [...]

2010-09-07T07:46:33-07:00September, 2010|Oral Cancer News|
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HPV-positive oropharnygeal cancer has better prognosis than tobacco-induced cancer

Source: www.enttoday.org Author: Alice Goodma Mounting evidence suggests that human papillomavirus (HPV)-positive oropharyngeal cancer has an improved prognosis compared with HPV-negative disease. The most recent supportive evidence comes from an analysis of a Phase III trial presented at the 2009 annual meeting of the American Society of Clinical Oncology. Our study showed that HPV status is as strong a predictor of outcome as cancer stage for patients with oropharyngeal cancers, even after considering other factors such as age and smoking history, said lead author Maura Gillison, MD, PhD, Professor of Hematology and Oncology, Epidemiology, and Otolaryngology at Ohio State University in Columbus. Dr. Gillison said that tumor HPV status should now be part of the routine workup of patients with oropharyngeal cancers. Oropharyngeal cancers are mainly attributable to chronic tobacco use and smoking, or to HPV infection. Retrospective analyses, meta-analysis, and small trials have suggested that HPV-positive oropharyngeal cancer is a distinct entity, and the present Phase III study provides the most compelling evidence, she said, because it is the largest study to date. It is not clear why HPV-associated oropharyngeal cancer has a better prognosis. In the trial, HPV-positive patients were younger, mostly Caucasian, and had improved performance status and smaller tumors. Dr. Gillison said that these factors could have a positive influence on survival. Survival Benefit The retrospective correlative analysis of Radiation Therapy Oncology Group (RTOG) 0129, presented by Dr. Gillison, focused on outcome according to HPV status. The randomized study included 206 patients with cancers positive for [...]

2010-08-16T10:19:03-07:00August, 2010|Oral Cancer News|
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ASCO: Second study links HPV to mouth cancer outcomes

Source: www.medpagetoday.com/ Author: Michael Smith, North American Correspondent, MedPage Today Human papillomavirus (HPV) infection predicts a better chance of survival in patients with oropharyngeal squamous cell carcinoma, researchers said. In a retrospective analysis of a major radiation therapy trial, more than four-fifths of patients whose tumors were HPV-positive were alive three years after treatment, according to Maura Gillison, MD, PhD, of Ohio State University in Columbus, and colleagues. In contrast, fewer than six of 10 patients with HPV-negative tumors were still alive at the three-year mark, Gillison and colleagues reported online in the New England Journal of Medicine, in an article released to coincide with a presentation at the American Society of Clinical Oncology meeting here. The study follows a report earlier at the meeting that found a similar pattern among patients enrolled in a chemotherapy trial. The virus is, of course, well known to cause cervical cancer. The New England Journal study adds to the evidence that "HPV-positive oropharyngeal squamous-cell carcinoma represents a distinct clinicopathological entity associated with a better prognosis than HPV-negative oropharyngeal squamous-cell carcinoma," said Douglas Lowy, MD, of the NIH, and Karl Munger, PhD, of Brigham and Women's Hospital in Boston. Writing in an accompanying editorial, Lowy and Munger argued that if the diseases are distinct, "their treatment or prevention might benefit from different approaches." One possibility, they said, would be to target HPV proteins to treat the disease in some patients, while prevention might involve vaccination against the virus. Gillison and colleagues looked at the [...]

2010-06-07T16:09:05-07:00June, 2010|OCF In The News, Oral Cancer News|
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Docetaxel suppresses invasiveness of head and neck cancer cells in vitro

Source: Cancer Sci, February 22, 2010 Author: Y Kogashiwa et al. The combination of docetaxel, cisplatin, and fluorouracil significantly enhances the survival of head and neck cancer patients compared to cisplatin and fluorouracil. We hypothesized that docetaxel may affect invasiveness of the head and neck cancer cells in addition to its tumor-killing effect. Two different head and neck cancer cell lines (HEp-2 and Ca9-22) were treated with docetaxel at IC(10) and IC(50) concentrations. Cell migration and invasive growth was evaluated by wound healing assay and three-dimensional (3D) culture of multicellular tumor spheroids, respectively. Expression levels of possible downstream effectors for cell migration/invasiveness were measured by immunoblotting in conditions with or without docetaxel. Docetaxel, but not cisplatin, suppressed filopodia formation compared with no treatment (control) condition. Consistent with this, docetaxel suppressed two-dimensional (2D) cell migration and 3D cell invasion compared with control or cisplatin. Only docetaxel treated cells exhibited thick tubulin bundle and had lower activity of Cdc42, a member of the Rho family of small GTPases. In conclusion, Docetaxel treatment suppressed migration and invasiveness of head and neck cancer cells in vitro, which is likely to be mediated by regulating Cdc42 activity. Authors: Y Kogashiwa, H Sakurai, T Kimura, and N Kohno Authors' affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan

2010-04-06T11:22:56-07:00April, 2010|Oral Cancer News|
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