squamous cell carcinoma

April: Oral Cancer Awareness Month

Source: Aspen Dental

April is Oral Cancer Awareness Month. According to Brian Hill, founder and executive director of the Oral Cancer Foundation, as many as 40,000 people in the United States will be told they have oral or pharyngeal cancer in 2012. Some of them may be sitting in your dental chair today. With one person dying of oral cancer every hour of every day, and more than 50% of those diagnosed not living more than 5 years, this is a reminder to screen every patient yourself, and encourage your dental hygiene staff to do the same.

The Statistics

About 100 people are diagnosed with oral cancer every day in the United States. Few people are aware that the death rate for oral cancer is higher than for many other types of cancers, which is because oral cancer often is not discovered until it has reached later stages. This is particularly true for human papilloma virus number 16 (HPV16)-related oral cancer, which occurs most frequently in the posterior areas of the mouth—at the base of the tongue, around the tonsils, and in the oropharynx—where it’s harder to spot without a very thorough exam. To further complicate things, HPV16-related cancer does not always present the tell-tale physical characteristics, including lesions, that are easily distinguished from healthy oral tissues. This is not good news, because HPV16 has reached epidemic levels in the United States: of the 37,000 incidences of oral cancer, about 20,000 (up to 60%) can be linked to HPV, according to Hill.

Oral cancer accounts for 85% of the cancers grouped under “head and neck” cancers. If the number of larynx cancer cases (for which the historic risk factors; tobacco and alcohol are the same) is added to the oral cancer category, we’re now talking 50,000 people diagnosed yearly and 13,500 deaths per year in this country. More than 640,000 new cases occur worldwide annually. These stats do not include brain cancer, which is its own category.

“Late discovery and misdiagnosis are the biggest problems,” Hill says. “I’m a very typical example of this.” Hill was misdiagnosed with an infection by a physician when a painless lump appeared on the side of his neck. When it had not resolved after a course of antibiotics, Hill, who had a background in dentistry, insisted on having a needle aspiration biopsy. Testing resulted in a diagnosis of HPV16-related squamous cell carcinoma, a very deadly cancer. Fourteen years after extensive surgery, and both radiation and chemotherapy, he has since heard from literally thousands of people that they were misdiagnosed more than once, told not to worry about it, or were merely given antibiotics. “Why are so many people diagnosed late?” Hill asks. “Because, according to one study,probably under 20% of dentists are performing oral screenings.” 1 Another problem is that public awareness about oral cancer, its early signs and symptoms, and its changing etiology, is low. Additionally, oral cancer has historically been linked to long-term tobacco use and high alcohol consumption (or a combination of both), with associated lesions usually seen in the anterior areas of the oral cavity. With the prevalence of HPV16-related oral cancer increasing at an alarming rate, and tobacco-related cancers on the decline, it is critical that dental and medical professionals re-educate the public to understand the current risk factors and the need for an annual professional screening.

The Impact of HPV16

It was reported in 2009, before the advent of HPV-related cancers, that oral cancer incidence rates were more than twice as high in men as in women, and both were on the decline.2 That was before HPV-infected individuals became the fastest growing segment of the oral cancer population. HPV16 is a human papillomavirus related to more than 150 other HPV versions, over 40 of which can be easily sexually transmitted.3 Nine of these are known to be cancer causing. HPV’s were directly linked to cervical cancer, also squamous cell carcinoma, which was the number one killer of women in 1948. “Using the cervical cancer model, once ‘opportunistic’ screening and PAP testing became routine, the cervical cancer death rate dropped 71% in 10 years,” Hill notes. “We have no ‘viruscide’. But we do have an HPV vaccine that can be administered before young people become sexually active.” This is important information to share with patients, because 50%-80% of Americans will have HPV in their lifetime according to the Center for Disease Control and Prevention (CDC). About half of all men and more than 3 out of 4 women will be diagnosed with it at some point.4

Detection vs Diagnosis

Signs and symptoms or oral cancer, if there are any, range from a sore area or lesion that bleeds easily, a lump or thickening of tissues in the mouth or neck, ear pain, indurations or hard spots in the mucosa, or a red or white patch or ulceration that does not resolve within 2 weeks. If any of these are evident, the patient should return within 7-14 days to confirm either persistence or resolution. Later symptoms include difficulty chewing, swallowing, and/or moving the tongue or jaws.2

Early stage (1 and 2) lesions, which may not be readily evident during a routine exam, usually are asymptomatic and often mimic other conditions.5 It is important for dentists to acknowledge that malignant and benign lesions are virtually indistinguishable clinically, and their biological relevance cannot be assessed based on their appearance.5 Most resources advise referring any persistent abnormalities to a specialist. “We have a highly defined referral system in dentistry,” Hill points out. “You don’t have to learn anything new; you don’t have to be the expert. You just have to refer suspect tissues up the professional chain for proper evaluation/biopsy. There are many kinds of oral lesions. You may see only 3 cancer cases in 20 years of practicing dentistry, but every time you find something, especially in stage 1 or 2, you have the opportunity to save a life. Dentists are the first line of defense.”

The American Cancer Society estimated in 2009 that almost 90% of oral cancers are squamous cell carcinomas, and more than 97% of these cancers occur in adults 35 years and older.5 People ranging in age from 25-50 who never smoked are the fastest growing group being diagnosed with HPV16-related oral cancer.6

Standard treatment usually involves radiation therapy and surgery, and often chemotherapy.2 Relative survival rates vary by stage at the time of diagnosis—in 2009, about 83% survived 1 year after diagnosis, 60% 5 years after diagnosis, and 49% after 10 years.2 However, today, the 5-year survival rate is only about 57% when you include all stages of the disease at time of discovery. This high death rate is directly tied to late discovery, when treatments are less effective.7 Studies reveal that oral and pharyngeal cancer are diagnosed at a localized stage in only one-third of patients in the United States.5 It’s time to make a difference.

The Oral Cancer Foundation

The Oral Cancer Foundation (OCF) is a national public service, non-profit organization dedicated to oral cancer prevention, education, research, advocacy, and patient support activities. Its website, www.oralcancerfoundation.org, provides vetted information about rates of occurrence, risk factors, signs and symptoms, treatments, current research, complications, nutrition, clinical trials, related news, links to other sources, and treatment institutions. A free, anonymous, 8700-member patient/survivor discussion forum is open to the public, providing insights and inspiration. OCF also has a free RSS oral cancer news feed you may subscribe to which is updated several times a week. OCF is a valuable resource for patients, students, and practicing medical and dental professionals.

Visit oralcancerfoundation.org to learn of its Oral Cancer Awareness Month initiatives (such as hosting a free screening event in April), and find information to share with your patients.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

Epidermal Growth Factor Receptor and the Changing Face of Oropharyngeal Cancer

Source: Journal of Clinical Oncology

To the Editor:

In their article, Chaturvedi et al1 document the rise in human papillomavirus (HPV) –associated cancers as a proportion of squamous cell carcinomas of the oropharynx over the last 25 years. The contemporary figures are mirrored by two recent British studies2,3 demonstrating that the majority of oropharyngeal cancers are now HPV related.

In the accompanying editorial,4 Mroz et al rightly highlight the importance of evaluating HPV vaccination for both men and women in the light of these data and lament the lack of significant improvement in the outcomes for non–HPV-associated head and neck cancers. However, they also suggest that the benefit of targeting epidermal growth factor receptor (EGFR) through concurrent cetuximab may be confined to HPV-associated tumors. Although EGFR expression per se does not correlate closely with response to cetuximab, there is increasing evidence of an inverse correlation between p16INK4A expression (as a marker of HPV association) and EGFR expression shown by immunohistochemistry.5,6 Though suppressed by viral oncogenes, HPV-associated tumors retain wild-type P53,7 and patients with this tumor type have demonstrated excellent survival with existing protocols such as concurrent chemoradiotherapy or surgery with postoperative radiotherapy. Conversely, non-HPV tumors, harboring a range of mutations,8 may respond less well to DNA-damaging agents, but patients with these tumors might benefit from the addition of concurrent EGFR blockade to radiotherapy. Data from the recent SPECTRUM (Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer) study of adding another EGFR-targeting monoclonal antibody, panitumumab,9 suggest that in the metastatic setting at least, only patients with HPV-negative tumors benefit from a combination of palliative chemotherapy and an anti-EGFR strategy. If confirmed in sample sets containing non-HPV tumors treated with EGFR-targeting agents in combination with radiotherapy, this could open the door to the improvements urgently needed in HPV-negative oropharyngeal cancers, where an older demographic and greater burden of comorbidities make the uncomplicated and complete delivery of concurrent chemoradiotherapy challenging.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

March, 2012|Oral Cancer News|

Robotic surgery less invasive on HPV-related oral cancers

Source: Dr.Bicuspid.com

March 1, 2012 — Robotic surgery conducted through patients’ mouths provides excellent results in removing squamous cell carcinoma at the back of the throat, especially in patients with HPV, according to a new Mayo Clinic study (Mayo Clinic Proceedings, March 2012, Vol. 87(3), pp. 211-212).

“We were surprised that the cancer cure results were even better than the traditional treatments that we have been doing, but that is probably almost as much of a matter that these cancers are HPV-mediated for the most part, and they respond much better to treatment,” said study author Eric Moore, MD, a head and neck surgeon at Mayo Clinic. “Importantly, the treatment preserved patients’ ability to swallow, and their speech performance was excellent.”

Dr. Moore and his team followed 66 patients with oropharyngeal cancer who underwent transoral robotic surgery with the da Vinci robotic surgical system. Every few months, the patients underwent imaging studies, scans, and exams to determine if cancer was recurring.

After two years, the researchers found that the patients’ survival rates were greater than 92%, which is as high as some other surgical and nonsurgical treatments for oropharyngeal cancer.

Because traditional surgery techniques to remove throat tumors can be traumatic, requiring cutting and reconstructing the mandible, neck, and tongue, the researchers were also interested in patients’ healing after robotic surgery.

“We found that with transoral robotic surgery, 96% of patients could swallow a normal diet within three weeks of treatment,” Dr. Moore said. Less than 4% required a gastrostomy tube, he added.

The study provides preliminary data illustrating that the robotic surgery is a viable treatment option, Dr. Moore concluded. Continuing research involving multiple medical centers will investigate transoral robotic surgery in a larger population of patients with oropharyngeal cancer.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

March, 2012|Oral Cancer News|

Adaptive radiotherapy may benefit patients with head and neck cancer

Source: News-Medical.net

Researchers led by a senior investigator at Hofstra-North Shore LIJ School of Medicine and The Feinstein Institute for Medical Research have released initial findings from a first-of-a-kind clinical trial in adaptive radiotherapy (ART) for head and neck cancer. The trial, sponsored by the National Cancer Institute, provides evidence that ART may benefit patients with less technical difficulty than previously believed. The findings of this trial were released online in advance of publication in the International Journal of Radiation Oncology Biology Physics.

Physicians commonly use radiotherapy to treat squamous cell carcinoma of the oropharynx (back of throat). Current standard-of-care treatment is called intensity-modulated radiotherapy, or IMRT. IMRT allows physicians to “sculpt” radiation to fit the anatomy of individual patients. Although appealing, this technique has a crucial Achilles’ heel – it is based entirely on a CT or MRI scan taken before actual treatment begins. Since a typical course of radiation treatment for oropharynx cancer lasts 6-7 weeks, standard IMRT cannot compensate for common changes that take place in a patient’s body during this time, such as weight loss, shrinkage of tumor, or gradual movement of normal tissues. Recent work suggests that the inability of standard IMRT to keep up with these changes may lead to unanticipated toxicity, or potentially worse, missing of tumor.

For this new trial, which was conducted at the University of Texas M.D. Anderson Cancer Center, investigators started patients on standard IMRT. They then took CT scans while patients were lying in the radiation treatment room each day so they could monitor changes in tumor and normal tissues during the entire course of treatment. Through computerized techniques, the investigators “adapted” (thus the name “adaptive radiotherapy“) treatment if they noticed significant tumor or body changes that could affect quality of treatment. Most strikingly, the group found that most patients required only one, or at most two adaptions of IMRT to maintain treatment quality.

“This is the first prospective clinical trial of its kind to gauge how “refitting” of IMRT to a patient’s body actually impacts care for a patient who has head and neck cancer,” noted David Schwartz, MD, vice-chair of radiation medicine at the North Shore-LIJ Health System, associate professor at the Hofstra North Shore-LIJ School of Medicine, and a senior investigator at The Feinstein Institute for Medical Research. “What most encouraged us was that ART appears effective with only 1 or 2 additional replans. This means that ART does not have to be overly burdensome or expensive to make a difference. This is something that is feasible, and could eventually make a real-world difference in many clinics.”

“ART keeps radiation treatment tightly fitted to a patient’s body, almost as if it were being shrink-wrapped,” Schwartz added. “It is as individualized as our current treatment can realistically be.”

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

February, 2012|Oral Cancer News|

PET/CT Detects Early Recurrence of Head and Neck Cancer

Source: Elsevier Global Medical News

Routine use of positron emission tomography/computed tomography scans can detect locoregional recurrences of squamous cell carcinoma of the head and neck before they became clinically apparent, according to a retrospective chart review of 234 patients who had been treated with chemoradiation between 2006 and 2010.

The finding suggests that routine use of positron emission tomography/computed tomography (PET/CT) may improve the outcome of salvage therapy, said Dr. Yasir Rudha, who reported the study at the Multidisciplinary Head and Neck Symposium sponsored by the American Society for Radiation Oncology.

PET/CT was associated with a high false positive rate, which should be considered when ordering radiological exams and biopsies, but a negative post therapy PET scan appears to be an excellent predictor of freedom from future locoregional recurrence, said Dr. Rudha of St. John Hospital/Van Elslander Cancer Center, Grosse Pointe Woods, Mich.

The technology is relatively new, and its use for routine follow-up in patients with head and neck cancer is still controversial, he acknowledged. “Only a few publications have reported the value of PET examination at a fixed time interval after the end of treatment,” he said. “PET scan is often ordered in our hospital as a routine surveillance tool following successful completion of treatment.”

The review of charts for all 234 patients identified 45 who had achieved clinical no-evidence-of-disease status at the time of post treatment imaging. In this group, PET/CT scanning at 6-9 weeks identified 15 patients with abnormalities that required further evaluation. Of those, eight patients (53%) were proven to have malignancies based on biopsy findings: six showed occult persistent disease at the primary site, and two were diagnosed with regional lymph node recurrence and colon cancer, respectively.

In the remaining seven cases, imaging findings were shown to represent false positive results with unnecessary work-up and/or biopsy evaluation. All patients who had negative PET/CT scans remained free from locoregional relapse at the time of last follow-up.

Thus, Dr. Rudha said the true positive rate for routine PET/CT surveillance in head and neck cancer patients was estimated as 8/15, or 53%, and the false positive rate as 7/15, or 46%.

”With malignancies found in 53% of abnormal scans in this study, our research proves that PET/CT scans are valuable as routine follow-up and as a surveillance method for head and neck cancer patients … However, since the rate of false positives was 46%, caution should be shown when ordering biopsies after abnormal scans to prevent excessive unnecessary biopsies,” he said.

During a press briefing, Dr. Rudha said that the 46% false positive rate was lower than what he and his colleagues expected. “Actually we expected the false positive ratio to be about 90%,” he said.

In an interview, he said that at his institution patients with positive PET/CT scans at 6-9 weeks post surgery are followed in a variety of ways, depending primarily on the PET standard uptake volume (SUV). If low, the patient might undergo another PET scan at about 3 months. But if SUV is high, the patient would likely be referred for another test such as magnetic resonance imaging, ultrasound, or biopsy at the site of recurrence.

However, if the post surgery PET/CT scan is negative, “according to this research, it gives a great indication that the patient is free from disease and the treatment is successful.”

PET/CT is being evaluated in a variety of different situations, said Dr. David Raben, professor of radiation oncology at the University of Colorado, Denver. “We’re still looking at programs that are combining PET/CT imaging with functional DCI/MRI imaging in part to help oncologists find the tumor volume and define how to plan our treatments in regard to what the target volumes are both on the ipsilateral and contralateral side of the neck,”

”In the post treatment setting, it’s been absolutely critical for us in terms of determining who should go on to further evaluation or who could be watched carefully. For instance, a University of Maryland group has shown quite nicely that in patients who have a clinical complete response and a complete response by PET imaging, almost all those patients do not need a neck dissection (Head Neck 2010;32:46-52). … That’s a significant savings in health care costs, whereas in the past, almost all of those patients 10-15 years ago would have gone on to a neck dissection,” he said.

The current study also offers important data, Dr. Raben continued. “I believe 6 weeks is too early. We recommend a minimum of 8 weeks, preferably 12 weeks post treatment, to allow inflammation to subside,” he said. “That may help reduce the false positive rate. I think use of PET/CT continues to evolve, and hopefully additional functional imaging studies will help us nail down which patients need to go on to further treatment or biopsy.”

Dr. Rudha and his coauthors and Dr. Raben stated that they had no disclosures.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.


February, 2012|Oral Cancer News|

Head and neck cancer carries substantial comorbidity burden

Source: MedWire News

People with head and neck cancer experience a high burden of both acute and chronic comorbidity, shows an analysis of a large Dutch population-based cohort.

The researchers therefore advise clinicians to account for patients’ comorbidity burden when assessing the risk-benefit profile for different treatment options.

Sarah Landis (GlaxoSmithKline, London, UK) and co-workers analyzed information on 1499 patients with squamous cell carcinoma of the head and neck (SCCHN) living in the Netherlands.

For each patient they calculated prevalence and incidence rates of eight comorbid conditions: cardiovascular disease, asthma/chronic obstructive pulmonary disease (COPD), liver disease, diabetes, anemia, pneumonia, depression, and other malignant disease.

Rates of the same eight conditions were also calculated in a control population of 5996 cancer-free individuals matched for age and gender.

Writing in the journal Head and Neck, Landis et al report that the mean age of the SCCHN cohort was 62 years and two-thirds were male. The site of cancer was the oral cavity in 610 patients, the pharynx in 317, and the larynx in 572.

The most prevalent comorbidities in patients with SCCHN were cardiovascular disease (41%) and asthma/COPD (12%); the other comorbidities were prevalent in less than 10% of patients.

Notably, in the period of 12 months prior to the index date, patients with SCCHN were between two and four times as likely as cancer-free controls to have any of the comorbidities investigated, the authors remark.

In terms of incidence, rates of all comorbidities (with the exception of other malignant diseases) were generally highest during the first 6 months after SCCHN diagnosis and declined steadily during follow-up.

The researchers then calculated hazard ratios (HRs) for each of the comorbidities. They found that, compared with the healthy control population, patients with SCCHN had a significantly higher risk for all comorbidities except diabetes, with HRs ranging from 2.0 for asthma/COPD to 13.3 for pneumonia.

Interestingly, the increased risks in SCCHN patients persisted throughout the entire follow-up period (median 3.8 years) for anemia, depression, pneumonia, asthma/COPD, and other malignant diseases. By contrast, the risks for cardiovascular diseases and diabetes among patients with SCCHN approached that of cancer-free controls within 12 months of diagnosis.

Landis et al conclude: “This study quantifies the significant burden of comorbidity among patients with SCCHN. Understanding which comorbidities are most likely to arise after diagnosis supports balanced treatment decision making that maximizes patient outcome while limiting the likelihood of side effects or worsening of pre-existing conditions.

“Future longitudinal studies aimed at understanding the impact of specific comorbid events on patient outcome and survival are warranted.”

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

February, 2012|Oral Cancer News|

Third Head and Neck Indication for Erbitux

Source: The ASCO Post, January 1, 2012, Volume 3, Issue 1, Matthew Stenger

 

In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.Cetuximab (Erbitux) was recently approved by the FDA for use in combination with platinum-based therapy plus fluorouracil (5-FU) for the first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck.1-3 Cetuximab has prior indications in combination with radiation therapy in locally or regionally advanced squamous cell head and neck cancer and in recurrent or metastatic head and neck cancer that has progressed after platinum-based therapy. It also has indications in colorectal cancer.

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The most recent approval is based primarily on results of a study conducted outside the United States in 442 patients with metastatic or locally recurrent squamous cell carcinoma of the head and neck who were not suitable for curative treatment with surgery or radiation. The study used a European Union (EU)-approved cetuximab rather than the U.S.-approved cetuximab (Erbitux). Erbitux provides approximately 22% higher exposure than the EU-approved cetuximab; these pharmacokinetic data, together with the results of the study conducted in Europe and other data using Erbitux establish the safety and efficacy of Erbitux at the recommended dose.In this trial, the addition of cetuximab (n = 222) to platinum-based therapy plus 5-FU (n = 220) significantly increased median overall survival from 7.4 to 10.1 months, representing a 20% reduction in risk of death (HR = 0.80, P = .034), and significantly increased median progression-free survival from 3.3 to 5.5 months, representing a 43% reduction in risk of disease progression (HR = 0.57, P < .0001). Objective response rates were 35.6% in the cetuximab group and 19.5% in the chemotherapy-alone group (P = .0001).


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How It Works

Cetuximab is an IgG1 monoclonal antibody that inhibits ligand-binding to the epidermal growth factor receptor (EGFR) on both normal and tumor cells. Binding of cetuximab to EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased production of matrix metalloproteinase and vascular endothelial growth factor. In cells with activating KRAS mutation, however, the KRAS proteins are continuously active and are independent of EGFR regulation. Cetuximab also stimulates antibody-dependent cell-mediated cytotoxicity and enhances the activity of a number of chemotherapeutic agents, including cisplatin.

How It Is Given

For the new indication, the recommended dose is 400 mg/m2 as a 120-minute IV infusion, with a maximum rate of 10 mg/min, on the day that platinum-based therapy plus 5-FU is started. The infusion must be completed 1 hour prior to beginning platinum-based therapy plus 5-FU. The subsequent weekly dose is 250 mg/m2 over 60 minutes until disease progression or unacceptable toxicity.Patients should be premedicated with an H1 antagonist (eg, diphenhydramine, 50 mg) IV 30 to 60 minutes before the first dose of cetuximab; premedication for subsequent doses depends on clinical judgment and presence/severity of prior infusion reactions. The infusion rate should be reduced by 50% for grade 1 or 2 or nonserious grade 3 infusion reactions. Cetuximab should be immediately and permanently discontinued for severe infusion reactions.In cases of severe acneiform rash, administration should be delayed by 1 to 2 weeks, and cetuximab discontinued at the fourth occurrence. The weekly dose should be reduced to 200 mg/m2 after the second occurrence and 150 mg/m2 after the third.Cetuximab should be administered via infusion pump or syringe pump and through a low protein-binding 0.22-micrometer in-line filter.

Safety Profile

Cetuximab carries a boxed warning for infusion reactions and cardiopulmonary arrest. Serious infusion reactions occurred in approximately 3% of patients in clinical trials, with fatal outcome in less than 1 in 1,000 cases. In patients with squamous cell carcinoma of the head and neck receiving cetuximab, cardiopulmonary arrest or sudden death occurred in 2% of those receiving radiotherapy and in 3% of those receving platinum-based therapy plus 5-FU. Serum electrolytes, including magnesium, potassium, and calcium, must be carefully monitored during and after cetuximab administration.In the trial supporting the current indication, the most common adverse reactions (≥ 25%) in patients in the cetuximab group were nausea, anemia, vomiting, neutropenia, rash, asthenia, diarrhea, and anorexia; conjunctivitis occurred in 10%. Other adverse reactions, sometimes severe, caused by cetuximab included infusion reactions, hypomagnesemia, hypocalcemia, and hypokalemia. Death attributed to cardiovascular event or sudden death was reported in 3.2% of the patients in the cetuximab group and in 1.9% in the chemotherapy alone group.

 This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

January, 2012|Oral Cancer News|

Quality-of-Life Outcomes in Transoral Robotic Surgery

Source: SAGE Journals Online

Abstract

Objective. To report long-term, health-related quality-of-life (HRQOL) outcomes in patients treated with transoral robotic surgery (TORS).

Study Design. Prospective, longitudinal, clinical study on functional and HRQOL outcomes in TORS.

Setting. University tertiary care facility.

Subjects and Methods. Patients who underwent TORS were asked to complete a Head and Neck Cancer Inventory before treatment and at 3 weeks and 3, 6, and 12 months postoperatively. Demographic, clinicopathological, and follow-up data were collected.

Results. Sixty-four patients who underwent TORS were enrolled. A total of 113 TORS procedures were performed. The mean follow-up time was 16.3 ± 7.49 months. The HRQOL was assessed at 3 weeks and at 3, 6, and 12 months, with a response rate of 78%, 44%, 41%, and 28%, respectively. TORS was performed most frequently for squamous cell carcinoma (88%). There was a decrease from baseline in the speech, eating, aesthetic, social, and overall QOL domains immediately after treatment. At the 1-year follow-up, the HRQOL scores in the aesthetic, social, and overall QOL domains were in the high domain. Patients with malignant lesions had significantly lower postoperative HRQOL scores in the speech, eating, social, and overall QOL domains (P < .05). Patients who underwent adjuvant radiation therapy or chemotherapy and radiation therapy had lower postoperative scores in the eating, social, and overall QOL domains (P < .05).

Conclusion. The preliminary data show that patients who undergo TORS for malignancies and receive adjuvant therapy tend to have lower HRQOL outcomes. TORS is a promising, minimally invasive, endoscopic alternative surgical treatment of laryngopharyngeal tumors.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

December, 2011|Oral Cancer News|

FDA Approves Cetuximab for Late-Stage Head and Neck Cancer

Source: The Oncology Report

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for “recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU,” according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for “locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy,” and for “recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

“Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. “Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible,” he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study “and other clinical trial data establish the efficacy of Erbitux at the recommended dose,” according to the revised prescribing information posted on the FDA Web site.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

November, 2011|Oral Cancer News|

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 as many treatment options available as possible.”

EXTREME Trial

The safety and effectiveness of cetuximab for this indication is based on the results of a multicenter clinical study — the Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME) trial. The results of this study were first reported at the 2007 meeting of the American Society of Clinical Oncology. At the time, experts in the field predicted that they would change clinical practice. The results were subsequently published in 2008 (N Engl J Med. 2008;359:1116-1127).

Cetuximab was granted approval by the European Commission in November 2008 for the treatment of first-line recurrent and/or metastatic head and neck cancer on the basis of the EXTREME study.

The trial involved 442 patients with untreated recurrent or metastatic squamous cell carcinoma of the head and neck; approximately 60% of the cohort had not received any previous chemotherapy. All patients received chemotherapy with a platinum agent (cisplatin or carboplatin, chosen by the investigator) plus infusional 5-fluorouracil. Half of the patients were randomized to also receive cetuximab.

On average, patients who received cetuximab plus chemotherapy survived longer than those who received chemotherapy alone (10.1 vs 7.4 months; hazard ratio [HR] for death, 0.80; P = .04).

The addition of cetuximab also significantly improved median progression-free survival (3.3 vs 5.6 months; HR for progression, 0.54; P < .001) and increased the response rate (20% vs 36%; P < .001).

“I think these data support the notion that we have a new standard treatment for patients with recurrent and/or metastatic head and neck cancer,” lead researcher Jan Vermorken, MD, PhD, professor of oncology at Antwerp University Hospital, in Ghent, Belgium, told Medscape Medical News when the study was published. “I would recommend that every patient with recurrent head and neck cancer who is not a candidate for radiation or surgery now receive platinum-based chemotherapy plus cetuximab, if their condition allows them to tolerate this.”

Higher Risk Adverse Events

The most commonly reported adverse events in patients who received cetuximab included rash, pruritus, nail changes, headache, diarrhea, and respiratory, skin, and mouth infections. The addition of cetuximab also increased the rate of sepsis, which occurred in 9 patients treated with chemotherapy plus cetuximab but in only 1 patient treated with chemotherapy alone (P = .02).

Cetuximab has also been known to cause low serum magnesium, potassium, and calcium; in this study, the incidence of hypomagnesemia also increased (11 patients treated with chemotherapy plus cetuximab and 3 treated with chemotherapy alone; P = .05). Other adverse events, such as neutropenia, were reported at similar rates in both groups, and the authors note that these adverse effects are consistent with the adverse-effect profile of cetuximab.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

November, 2011|Oral Cancer News|