Monthly Archives: September 2011

New Study Indicates Tobacco Industry Was Aware of Their Own Products Dangers

Source: USA Today

A new study says tobacco companies knew for decades that cigarette smoke was radioactive and potentially carcinogenic.

Tobacco companies knew for decades that cigarette smoke was radioactive and potentially carcinogenic but kept that information from the public, according to a new study.

The tobacco industry began investigations into the possible effects of these radioactive particles, identified as polonium-210, on smokers as early as the 1960s, says the study by UCLA researchers who analyzed dozens of previously unexamined industry documents.

“I’ve not seen a document before that’s specifically cited the industry’s own internal research finding that sufficient levels of polonium-210 can cause cancer,” says Matt Myers of the Campaign for Tobacco-Free Kids. He says the study reinforces the need for the U.S. Food and Drug Administration to scrutinize tobacco products. This week, the FDA began requiring tobacco companies to disclose detailed information about new products and changes to existing ones. The study, published in the peer-reviewed journal Nicotine & Tobacco Research, suggests the FDA make removal of the radioative particles from tobacco products a top priority. “We used to think that only the chemicals in the cigarettes were causing lung cancer,” said Hrayr S. Karagueuzian, lead author of the study. Now, Karagueuzian said, the industry’s own research shows that polonium-210, absorbed by tobacco leaves and inhaled by smokers, is dangerous. He said UCLA researchers found that the radioactivity could cause 120 to 138 deaths for every 1,000 regular smokers over a 25-year period. Karagueuzian said tobacco companies have declined techniques that could help eliminate polonium-210 from tobacco because of concern that smokers might lose the “instant nicotine rush” that fuels their addiction. David Sutton, spokesman for Philip Morris USA, the largest U.S. tobacco manufacturer, said the company does not add polonium-210 to its products. He said it’s a “naturally occurring element in the air” and has been widely discussed by the public health community for years. Industry critic Greg Connolly, who directs Harvard University’s Center for Global Tobacco Control, agrees that polonium-210’s risks have long been known. He said the study, however, reinforces the need for the FDA to regulate tobacco companies, adding, “The $64,000 question is: have they changed?”

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

September, 2011|Oral Cancer News|

New HPV Study Proves Vaccine’s Effectiveness

Source: Cancer.gov

A flurry of new research findings on a vaccine that prevents persistent infections by cancer-causing types of the human papillomavirus (HPV) has confirmed the vaccine’s efficacy and opened new avenues for research. The results, published in three separate reports, suggest that the vaccine could be simpler to administer and more affordable than researchers had previously thought—and that the vaccine may also have unexpected benefits.

All three studies originate from an ongoing clinical trial of Cervarix in Costa Rica. The new findings could help inform efforts to develop vaccination programs to prevent cervical cancer in countries around the world, the researchers said.

“The results from our trial and from other trials are extremely promising for this vaccine,” said Dr. Allan Hildesheim of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), a leader of the trial. “And they suggest that the impact of the vaccine may go beyond cervical disease.”

HPV infections can lead to cancers of the anus, vagina, vulva, penis, and some oropharyngeal cancers, in addition to cervical cancer. Cervarix is one of two HPV vaccines currently approved by the Food and Drug Administration to prevent these infections; the other is Gardasil.

One of the studies found that fewer than the prescribed three doses of Cervarix may offer the same protection as the full course. If confirmed, this could make vaccination easier to administer and more affordable, factors that are especially important in developing countries that have high rates of cervical cancer.

A second study from the Costa Rica HPV Vaccine Trial found that the vaccine may protect against anal HPV infections that could eventually lead to anal cancer. (See “Clinical Trial Shows Potential Benefit of HPV Vaccine for Anal Cancer.”)

Vaccine May Protect against Additional HPV Types

The third study confirmed that the vaccine is highly effective in preventing persistent infections with HPV types 16 and 18—the types targeted by Cervarix. The researchers also found evidence of “cross-protection” against other cancer-causing HPV types not targeted by the original formulation—HPV types 31, 33, and 45.

Testing an HPV Vaccine in the “Real World”The safety and effectiveness of Cervarix and the other FDA-approved HPV vaccine, Gardasil, were established in clinical trials sponsored by the vaccine makers. Nonetheless, NCI researchers and their long-time collaborators in Costa Rica decided to conduct an independent study of a vaccine in a real-world setting.A goal of the community-based trial was to collect data that could help with the implementation of cervical cancer prevention programs, said Dr. Herrero. “Our results could help the people who are planning vaccination programs to use this expensive vaccine in the most effective way possible.”

Launched in 2004, the randomized trial includes 7,466 women between the ages of 18 and 25 from two Costa Rican communities (approximately one-third of the women in the region). Participants initially received Cervarix or a vaccine against hepatitis A. At the end of 4 years, the researchers offered the HPV vaccine to women in the control group.

The researchers will continue to follow the participants. “This community-based trial provides avenues to study not just the theoretical efficacy of the vaccine but the impact of vaccination on a well-defined population,” said Dr. Hildesheim.

“This is a potential additional benefit from vaccination that we had not considered initially,” said Dr. Hildesheim, noting that suggestive evidence for cross-protection has been reported previously.

The third study, published online September 9 in Cancer Discovery, also provided further evidence that the benefit of vaccination is greatest when the vaccine is given to young women before they have initiated sexual activity.

“Exposure to HPV occurs as soon as sexual activity begins, so if you start vaccination after that point, you will miss an opportunity to prevent infections,” said the study’s lead author, Dr. Rolando Herrero, formerly the study director in Costa Rica and now with the International Agency for Research on Cancer.

The findings on age are consistent with previous studies, noted Dr. Kevin Ault of Emory University’s School of Medicine, who studies HPV but was not involved in the study. “As you age, you accumulate exposures to HPV, and, if the vaccine is given after you’ve been exposed to the virus, then it’s not going to be effective.”

Fewer Doses May Offer Protection

The discovery that two doses—and possibly even one—of Cervarix may protect against infection was possible because the study was done in a “real world” community setting. Many women in the trial (approximately 20 percent) received only one or two doses, often because of pregnancy or an unrelated health problem.

The researchers found, however, that all of the women who received the vaccine were protected equally—at least for the first 4 years after vaccination. Those results appeared online in the Journal of the National Cancer Institute on September 9.

“This study is terrific proof of concept,” said Dr. Eduardo Franco of McGill University’s Faculty of Medicine, who also studies HPV and was not involved in the research. “It suggests that countries could adopt the suboptimal dose regimens and still receive the same protection as the full course, assuming that the protection against lesions will also hold.”

At the end of 4 years, the researchers offered the HPV vaccine to women in the control group. The researchers will follow the trial participants to determine how long the protection lasts.

If the current results are confirmed, the costs of vaccination programs could drop. “Our results may have important implications for public health, although many questions remain unanswered,” said the study’s first author, Dr. Aimée Kreimer of DCEG.

For instance, how long one or two doses of the vaccine protect against HPV infection is not known. In addition, the findings may not apply to other vaccines or to other populations, such as people who are malnourished or lack strong immune responses, the study authors cautioned.

More Affordable and Sustainable Cervical Cancer Prevention

Costa Rica HPV Vaccine Trial team
The Costa Rica HPV Vaccine Trial team in Guanacaste, Costa Rica, at the start of the study in 2004.

“The importance of the current study is not so much for Costa Rica, which has cervical cancer screening programs, but for countries that have truly high incidences of cervical cancer and no screening,” Dr. Franco said. More follow-up is needed to show that the suboptimal doses translate into fewer cervical precancerous lesions for vaccinated women, he added.

This study “represents an important step on the road to more affordable and sustainable cervical cancer prevention programs,” wrote Dr. Cosette Marie Wheeler of the University of New Mexico in an accompanying editorial.

Few, if any, developing countries where cervical cancer is common can afford vaccination programs, said Dr. Herrero. But if countries can afford to vaccinate only certain groups, they need to know which ones would benefit most, he noted. As the current study shows, this group would likely be young women who are not yet sexually active.

“When we started more than 25 years ago, we were just discovering that HPV was the cause of cervical cancer,” said Dr. Herrero. “Today we have a tremendous amount of tools and knowledge, which make it possible to intervene in this disease.”

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

September, 2011|Oral Cancer News|

HPV Vaccine and Premarital-Sex Controversy

Source: The News Tribune

Some perspective is needed on the controversy over the Human Papillomavirus (HPV) vaccine that arose after a recent Republican presidential debate. The best way to do that is to take sex out of the equation.

Instead of preventing a sexually transmitted disease that can lead to cervical cancer in women and oral cancer in men, let’s say the HPV vaccine guarded against a fictional virus that caused breast cancer and prostate cancer.

Wouldn’t most parents jump at the chance to decrease the chances of their children contracting those potentially deadly cancers? Only the most hard-core anti-vaccine holdout would say no.

Which gets us back to the sex part of the HPV equation and why some otherwise rational people don’t think children should be inoculated against it. They oppose the HPV vaccine – Cervarix or Gardasil – because they fear that removing one of the consequences of premarital sex would encourage it.

It’s a weak argument. The fear of STDs and pregnancy hasn’t put much of a damper on teens having sex, so it’s hard to see why the chance of developing cancer several years down the road would slow them down. They also know that smoking can cause lung cancer, but many still do it.

Sometimes parents have to do things to protect kids from themselves – and teens from their hormones. Most young people will not wait until marriage to have sexual relations; parents who think not getting their children vaccinated against HPV will deter them from having sex are gambling with their lives.

The anti-vaccine argument is a specious one on another level: It can protect those who don’t have premarital sex, too. An unvaccinated person who is a virgin on his or her wedding night can catch HPV from an infected spouse.

According to the Centers for Disease Control, HPV is the most common STD in the United States; approximately half of sexually active Americans will be infected with at least one strain of HPV at some point in their life – and many don’t even know it.

In most cases, the body’s immune system clears out HPV within two years, but in others it can lead to genital warts and a variety of cancers. It can even be passed on to unborn babies. Each year, HPV causes cervical cancer in 12,000 women. The five-year survival rate, with treatment, is about 72 percent. But many cases are diagnosed too late.

Some of the HPV vaccine debate has been about whether it should be mandatory, as other vaccines are for school-age children. The State of Washington does not require the HPV vaccine (a series of three shots) but does recommend it for females beginning at age 11 or 12 and males beginning at age 9. The vaccine is most effective if given before sexual activity begins.

Mandatory or not, the HPV vaccine can save lives. Parents who want to protect their children from potentially deadly cancers should have them inoculated.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
September, 2011|Oral Cancer News|

MRI can show jaw invasion of oral cancer

Source: www.medpagetoday.com
Author: Charles Bankhead, Staff Writer

Oral cancer’s spread to the mandible could not hide from a type of MRI that may facilitate more accurate staging and surgical planning, data from laboratory studies suggest.

Sweep imaging with Fourier transform (SWIFT) provided fine-detail views of cortical and medullary bone specimens, and the images exhibited good correlation with histopathologic findings.

The in-vitro studies did not specifically examine SWIFT’s ability to identify early cortical bone invasion by oral cancer. However, the high-quality images obtained from the investigation provide reason for optimism, the researchers reported in the September issue of Archives of Otolaryngology Head and Neck Surgery.

“Our study is very promising in that it offers a SWIFT-based MRI technique for accurate assessment of minute changes of cortical and medullary bone in three dimensions without any ionizing radiation,” Ayse Tuba Karagulle Kendi, MD, of the University of Minnesota in Minneapolis, and co-authors wrote.

“It has the potential to precisely determine the extent of mandibular bone invasion associated with oral carcinoma. This study is a crucial step toward the goal of developing a robust and noninvasive approach for preoperative imaging of mandibular invasion,” they added.

Carcinoma of the oral cavity often spreads to the mandible, but in many instances does not cross the periosteal layer, obviating the need for mandibulectomy. Limitations of current imaging techniques often preclude determination of bone invasion prior to surgery, the authors noted.

MRI and CT have been used most often to evaluate mandibular invasion of oral cancer, but conventional protocols in both modalities have drawbacks that often lead to unsatisfactory images.

The development of SWIFT has created new opportunities for more accurate preoperative assessment of the mandible in patients with carcinoma of the oral cavity, the authors continued. Employing time-shared excitation and signal acquisition, SWIFT allows detection of signals with a broad range of relaxation times, facilitating finely delineated evaluation of cortical and medullary bone.

The principal advantage of SWIFT involves to its protocol of near-simultaneous excitation and acquisition.

“SWIFT obtains signal from cortical bone that has a fast-decaying signal, produces less distortion from magnetic susceptibility, and is less sensitive to motion artifacts,” Kendi and colleagues wrote.

To assess the feasibility of SWIFT to detect bone invasion by oral cancer, the authors examined two mandibular specimens obtained from segmental resections. Imaging was performed by means of a 9.4-T, 31-cm horizontal MRI scanner, using a home-built, single-loop, 25-mm coil.

The SWIFT sequence involved excitation bandwidth and acquisition spectral width of 125 kHz, repetition time of 2.5 milliseconds, and 128,000 projections. Acquisition time averaged about eight minutes.

“SWIFT images of the specimens revealed detailed bone and soft-tissue anatomy, including soft-tissue tumor, cortical bone, and medullary bone,” the authors wrote in describing the images they obtained. “SWIFT demonstrated fine anatomic details, including nutrient vessels and fine trabecular bone structure.”

“SWIFT produced evidence of cortical bone invasion as cortical interruption of the hypointense signal of cortical bone. Medullary bone invasion was also demonstrated in both specimens as extension of soft-tissue tumor into the medullary cavity and replacement of medullary fat with tumor,” they said.

SWIFT imaging provided finely detailed images of the demarcation between tumor-free medullary bone and tumor invasion, they added.

“The correlations between the histologic and MR images of these two specimens clearly show malignant invasion that has not been previously demonstrated with MR techniques,” Kendi and colleagues wrote in their discussion of the findings. “The data described in this report suggest that [SWIFT] MRI has a great deal of potential in accurately determining bone invasion preoperatively.”

Note:
1. Co-authors Djaudat S. Idiyatullin and Michael Garwood disclosed relationships with Steady State Imaging.
2. Idiyatullin, Garwood, and co-author Curtis A. Corum disclosed royalty interests in products related to the research described in the article.

Source: Archives of Otolaryngology Head and Neck Surgery, Kendi ATK, et al “Transformation in mandibular imaging with sweep imaging with Fourier transform magnetic resonance imaging” Arch Otolaryngol Head Neck Surg 2

September, 2011|Oral Cancer News|

Researchers find potential new therapeutic strategy for head and neck cancer

Source: www.uab.edu
Author: Beena Thannickal

Shih-Hsin (Eddy) Yang, M.D., Ph.D., an assistant professor in the UAB Department of Radiation Oncology and associate scientist in the experimental therapeutics program at the UAB Comprehensive Cancer Center, found a way to prevent head and neck cancer cells from repairing damage to DNA as they grow.

The findings, published by the Public Library of Science, showed that using the drug cetuximab can induce a DNA repair defect in head and neck cancer cells, and subsequently render the tumors susceptible to PARP inhibitors, which block enzymes that repair some types of DNA damage. This method prevents cancer cells from repairing the damage to the DNA as they grow, ultimately leading to cancer inhibition.

Poly ADP-ribose polymerases, or PARPs, are enzymes that repair some types of damage done to DNA. If they are inhibited, a backup repair pathway is initiated. Cetuximab, which inhibits the epidermal growth factor receptor signaling pathway of cancer cells, blocks this backup pathway and thus induces cancer cell death.

“The novelty of this finding is that we use targeted agents like cetuximab, in combination with a PARP inhibitor, ABT-888, both of which have already been tested to be safe in humans, to selectively kill tumors defective in DNA repair while potentially minimizing side effects,” says Yang.

Cetuximab was pioneered by James Bonner, M.D., chair of the UAB Department of Radiation Oncology, in a landmark multi-institutional clinical trial in head and neck cancer patients.

Because head and neck cancers are frequently aggressive, outcomes for patients are currently poor.

“This new potential therapeutic strategy may improve outcomes while keeping a favorable side effect profile,” says Yang.

September, 2011|Oral Cancer News|

HPV links to throat cancer in males

Source: www.thesimmonsvoice.com
Author: Emese Nemeth

Whether it is your first year or you are returning to college, there are always emails and pamplets about immunizations. While some vaccines are mandatory for public safety and health, vaccines such as Gardasil (also known as Silgard) for the Human Papillomavirus (HPV) are not.

While some may argue that it is relatively new vaccine and side effects may be uncertain, the benefits are starting to out-weigh the risks.

Gardasil was approved by the Food and Drug Administration (FDA) in 2006 to vaccinate against the four most common strains of HPV: types 6, 11, 16 and 18. Seventy percent of cervical cancer is caused by types 16 and 18. Types 16 and 18 are also known to cause HPV induced cancer of the anus, vulva, vagina and penis. The other two types, 6 and 11 are known to cause ninety percent of genital wart cases.

More recently, HPV has been linked to induce throat cancer, specifically, oropharyngeal cancer.

The American Society of Clinical Oncology also believes that “the annual occurrence of HPV-related oropharyngeal cancer among men will surpass that of cervical cancer among women by the year 2020.”

Why throat cancer is more prevalent in men is still unclear, but throat cancer still affects both sexes with 6,700 cases of HPV-positive oropharynx cancers in 2010. While cervical cancer is on the decline due to regular pap smears, throats are only examined due to pain or unusual symptoms.

Although Gardasil does not claim to prevent throat cancer, many experts believe that the vaccine can indirectly help prevent the cancer since the vaccine can protect against the same strains found in HPV related throat cancer.

While HPV related cancer cases are generally found in older adults who did not receive the vaccine and no longer qualify for it, these cancers, whether it is throat or cervical, can be preventable by receiving the vaccine.

Currently there is no test to determine whether a male partner carries HPV, leaving many women to find out through pap smears and abnormal cell growth, making this vaccine a viable option for protection against life-threatening cancers.

September, 2011|Oral Cancer News|

Trying to improve oral cancer treatment

Source: abclocal.go.com
Author: staff

It’s a journey that can begin in the mirror or at the dentist’s office.

A small lesion in the mouth or throat can turn out to be oral cancer. Notoriously known to be unpredictable, these cancers are hard to treat, but some young doctors at the New York University’s School of Dentistry are working to change that.

Oral cancers take one American life every hour and it’s because the unpredictability is a challenge. One person’s cancer might be slow growing and another’s wildly aggressive. It is impossible to tell which it is.

The NYU researchers are trying to decipher their instruction codes, their genomics. If doctors know which way the cancer is going, it can be stopped.

Halima Mohammed always carries water she constantly needs to drink. She is also a big consumer of fruits and vegetables. The reason: for nine years she has been fighting an oral cancer.

“I can’t have solid food so I get my nutrition from juices and most of these foods, especially the cabbage and the broccoli, are cancer fighting foods,” she said. The cancer has had a huge impact on her life. She’s already lost part of her tongue.

“It is from my research one of the most painful type of cancers that you can have and I’m not diminishing cancer and the types of cancer, there is a constant pain, constant pain,” said Mohammed. “It makes masticating difficult, swallowing difficult. You cannot have your favorite food anymore.”

But, Mohammed carries on, and now at the NYU College of Dentistry she’s helping the doctors find out more about cancers like hers.

It’s a challenge Dr. Brian Schmdit has taken on. He wears many hats at the school, among them he’s clinical director of the Bluestone Center for Clinical Research and he’s trying to understand more about oral cancers.

“Oral cancers are very tricky because they have highly variable clinical patterns where one patient can do very well after treatment and another patient does not do well,” he said. ”

That different behavior lies in the cancer’s genes and their genomics are the subject of his research, identifying and tracking the genes of the different cancer will eventually benefit patients.

“We’re hoping that it can be personalized, that we can use certain genetic markers in the cancer to tailor our treatment, to know which persons need aggressive treatment and which patients don’t need that aggressive treatment,” said Dr. Schmdit

With information about the cancer’s genes, doctors might be better able to predict who needs radiation, which needs no de dissection and prevent much of the overtreatment that now is necessary.

Oral cancer is found by dentists and patients, so if there is a pain or a ulcer or a suspicious area, get checked out for it.

September, 2011|Oral Cancer News|

Screening For HPV Persistence And Cervical Cancer Risk

Source: Medical News Today

Women over the age of thirty who test positive for HPV (Human Papillomavirus) should be re-tested two years later as part of cervical cancer screening, according to a study published online TK in the Journal of the National Cancer Institute.

HPV infection is the main cause of cervical cancer, although most women infected with HPV do not have cervical pathology and most HPV infections in women under the age of 25 go away. Screening is recommended for women over age thirty, and the type of HPV strain to screen for is important, since only some are associated with cervical cancer risk. Furthermore, only persistently detectable infections seem to be associated with cervical cancer risk. However, few long-term studies have been done on the persistence of these infections and cervical cancer risk.

To determine the association between persistent HPV infections and cervical cancer risk in women over the age of thirty, Hui-Chi Chen, PhD, of the Genomics Research Center of Academia Sinica in Taipei, Taiwan, and colleagues, followed a cohort of 11,923 women aged 30 over a period of 16 years. The women underwent baseline exams that included HPV DNA testing and cytological tests, and the tests were repeated two years later. Incidence of cervical cancer was determined from cancer registries and death registries. In total, 6,666 women participated in both baseline and second visits, whereas the other 3,456 patients underwent only the first exam.

The researchers found that the 16-year risk of cervical cancer was 6.2% for women infected with any carcinogenic strains of the virus. Among women who were persistently infected with carcinogenic HPVs over the 2-year testing period, cervical cancer risk was 12.4%, whereas the risk was only 0.14% for women who repeatedly tested HPV negative. Since the duration of infection, rather than one-time infection, predicts cervical cancer risk, the researchers said it would not be useful to repeat HPV testing more frequently than every two years for HPV-positive women.

The authors write, “Our findings suggest that, if upon testing an HPV infection is found, re-testing 2 years later would provide useful guidance as to the duration of infection and its risk.” Furthermore, they say, “The accumulated evidence suggests that it is time to include HPV testing in cancer screening programs for the general population.”

The researchers add that genotyping may improve HPV testing since certain carcinogenic HPV strains – namely HPV16 and HPV58 – were associated with a higher risk of cervical cancer than others.

In an accompanying editorial, Kevin A. Ault, MD, of the Department of Gynecology and Obstetrics at Emory University School of Medicine notes that “persistent HPV infection is an intermediate step in the development of cervical cancer.” He notes the study has several strengths, including long duration of follow-up, a large sample size, and linkage to the national cancer registry. He also adds that the study shows that women with negative HPV tests have a greatly reduced risk of developing cervical disease.      

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

Note from OCF:

It is highly likely that any testing that may be done in the mouth would fall under the same guidelines. It takes a protracted period, as much as two years, for women to clear the virus successfully. Oral DNA’s six month retest recommendation likely makes a lot of money for dentists and them but does not improve the paradigm. Also, as women age they have far fewer HPV infections.



September, 2011|Oral Cancer News|

Prevalence and Treatment Management of Oropharyngeal Candidiasis in Cancer Patients: Results of the French Candidoscope Study

Source: RedJournal.org

Purpose

The aim of this pharmaco-epidemiological study was to evaluate the prevalence of oropharyngeal candidiasis (OPC) in cancer patients treated with chemotherapy and/or radiotherapy.

Methods and Materials

Signs and symptoms of OPC were noted for all patients. Antifungal therapeutic management was recorded in OPC patients. Patients receiving local antifungal treatments were monitored until the end of treatment.

Results

Enrolled in the study were 2,042 patients with solid tumor and/or lymphoma treated with chemotherapy and/or another systemic cancer treatment and/or radiotherapy. The overall prevalence of OPC was 9.6% (95% confidence interval, 8.4%–11.0%] in this population. It was most frequent in patients treated with combined chemoradiotherapy (22.0%) or with more than two cytotoxic agents (16.9%). Local antifungal treatments were prescribed in 75.0% of OPC patients as recommended by guidelines. The compliance to treatment was higher in patients receiving once-daily miconazole mucoadhesive buccal tablet (MBT; 88.2%) than in those treated with several daily mouthwashes of amphotericin B (40%) or nystatin (18.8%).

Conclusion

OPC prevalence in treated cancer patients was high. Local treatments were usually prescribed as per guidelines. Compliance to local treatments was better with once-daily drugs.

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

September, 2011|Oral Cancer News|

Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial

Source: OncologyStat.com

TAKE-HOME MESSAGE

This randomized, placebo-controlled trial found that weekly palifermin was associated with decreased incidence and duration of severe oral mucositis in patients undergoing postoperative chemoradiotherapy for head and neck cancer.

SUMMARY

OncologySTAT Editorial Team

Combined chemoradiotherapy (CRT) offers improved outcomes after resection of locally advanced head and neck cancer but also increases the risk of oral mucositis, a debilitating and potentially dose-limiting toxicity of locoregional treatment. Palifermin, an analogue of keratinocyte growth factor, is FDA approved to prevent and treat mucositis in patients undergoing high-dose myelotoxic therapy for hematologic malignancies. In this multicenter, randomized, placebo-controlled trial, Henke et al evaluated whether palifermin reduces severe oral mucositis in patients undergoing CRT after surgical resection of locally advanced head and neck cancer.

Adult patients receiving postoperative CRT for high-risk stage II to IVB head and neck squamous cell carcinoma and with an ECOG performance status of 0 to 2 were enrolled from 38 centers in Europe, Australia, and Canada. Eligible study patients were stratified by tumor location (oral cavity/oropharynx or hypopharynx/larynx) and residual tumor (R0 [complete resection] or R1 [incomplete resection]). Study patients received a radiation dose of 60 Gy (R0 group) or 66 Gy (R1 group) plus cisplatin 100 mg/m2 on days 1 and 22, with the study drug administered 3 days prior to starting CRT and then weekly for 6 weeks. Patients who underwent radiotherapy after 6 weeks received an additional 100 mg/m2 of cisplatin and study drug. Oral saline rinses, topical anesthetics, feeding tubes, and hematopoietic growth factors were permitted; oral anti-inflammatory, antifungal, or antibiotic solutions were not permitted.

Patients initially were randomized to three treatment arms: weekly palifermin 180 µg/kg throughout CRT, weekly palifermin 180 µg/kg for 4 doses followed by weekly placebo through the remainder of CRT, or weekly placebo throughout CRT. However, adverse event monitoring led to a restart of the study after enrollment of the first 17 patients, with subsequently enrolled patients randomized to receive weekly palifermin 120 µg/kg (n = 92) or weekly placebo (n = 94) throughout CRT (for a minimum of 7 weeks); efficacy analyses were based on these 186 patients. The primary endpoint was the incidence of severe oral mucositis (WHO grade 3 or 4). Oral mucosa assessments occurred twice weekly throughout CRT and until resolution of oral mucositis to WHO grade ≤ 2 or week 15, whichever occurred first. Among secondary endpoints were duration of and time to onset of severe oral mucositis, incidence of grade ≥ 2 xerostomia at month 4, and incidence of treatment breaks (≥ 5 missed consecutive radiation fractions; chemotherapy delays or discontinuation). Time to disease progression and overall survival (OS) also were assessed.

Of 186 patients randomized to weekly palifermin 120 µg/kg or placebo, 79 in the palifermin arm (86%) and 82 in the placebo arm (87%) completed all oral evaluations. Patients in the palifermin group received a mean radiation dose of 59.7 Gy in a mean of 43.5 days and a mean cumulative cisplatin dose of 217.1 mg/m2. Patients in the placebo group received a mean radiation dose of 59.8 Gy in a mean of 43.2 days and a mean cumulative cisplatin dose of 206.4 mg/m2. Severe oral mucositis was observed in 47 patients (51%) in the palifermin group and 63 patients (67%) in the placebo group (P = .027). The median duration of severe oral mucositis was 4.5 days in the palifermin group vs 22.0 days in the placebo group (P = .037), and the median time to develop severe oral mucositis was 45 vs 32 days (P = .022), respectively. Incidence of grade ≥ 2 xerostomia at month 4, incidence of treatment breaks, time to disease progression, and OS did not differ significantly between the two groups.

In conclusion, weekly palifermin at a dose of 120 µg/kg was associated with reduced incidence, increased time to development, and decreased duration of severe oral mucositis in patients undergoing postoperative CRT for locally advanced head and neck cancer. However, differences in other efficacy endpoints were not statistically different in patients receiving palifermin. Further study of palifermin in this patient population is needed.

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

September, 2011|Oral Cancer News|