Monthly Archives: January 2004

Brachytherapy appears safe, effective in esophageal cancer

  • 1/27/2004
  • San Francisco
  • Edward Susman
  • Gastrointestinal Cancer Symposium

Esophageal cancer patients who are deemed poor surgical candidates may
benefit from endoscopically guided brachytherapy, as administered by a team
of radiation oncologists and gastroenterologists, according to a Canadian
study.
The multidisciplinary approach to treatment resulted in no esophageal
perforations in a series of 60 patients, reported Dr. Te Vuong and
colleagues at the first Gastrointestinal Cancers Symposium last week in San
Francisco.

The meeting was sponsored by the American Society for Therapeutic Radiology
and Oncology (ASTRO), the Society of Surgical Oncology (SSO), the American
Gastroenterological Association (AGA), and the American Society of Clinical
Oncology (ASCO).

According to the poster presentation from the McGill University Health
Centre in Montreal, the elderly patients with adenocarcinoma or squamous
cell carcinoma of the esophagus were treated with high-dose-rate
brachytherapy prior to external-beam radiation therapy. The patients
received 20-Gy doses in five fractions, prescribed at 1 cm from the source
to the initial tumor bed.

The tumor was identified by direct endoscopy. Radio-oblique clips were
placed above and below the tumor at the time of endoscopy for quality
control of tumor bed localization. Chemotherapy and/or reduced radiation
doses were dependent upon the individual patients’ performance status.

“After a median follow-up of 18 months for all 60 patients treated between
1996 and 2003, we saw about a 25% local recurrence rate of the cancer,”
Vuong said. “Historically we might expect to see a 50% recurrence in these
patients, so we believe that we have provided a benefit for them.” The
median survival was about 19 months, she added.

With regard to complications, there were no perforations or toxic deaths.
One patient developed a fistula. In other studies using brachytherapy for
esophageal cancer, perforations and fistulas have been reported at a 12%
rate, and the toxic death rate at 8%, Vuong noted.

Vuong, who is an associate professor of radiation oncology, stressed that
the interdisciplinary approach had much to do with the study’s success.

“(The gastroenterologists) were the people who placed the tubes and I think
their expertise allowed us to perform the treatment without suffering any
perforations,” she told AuntMinnie.com.

The researchers’ choice of using intracavity brachytherapy after
external-beam radiation was wise, commented Dr. Harry Bleiberg, director of
clinical research in the gastroenterology unit at the Institut Jules Bordet,
University of Brussels Cancer Center, Belgium.

“You can kill the tumor with radiation, but too much radiation will also
kill the patient. The procedure used by Dr. Vuong and colleagues at McGill
is an interesting way of getting more radiation to the tumor while sparing
healthy tissue,” Bleiberg said. However, he pointed out that few
institutions currently have the radiological equipment and expertise to
offer this treatment.

Still, “it is a very attractive way to reduce peripheral damage to healthy
tissues,” commented Dr. Carolyn Compton, Ph.D., the Strathkona professor of
pathology at McGill. “Using this method, the doctor can design a dose and
deliver radiation that will fit the individual’s tumor.”

Vuong said that a phase III study to confirm the group’s results was in the
works.

OCF Note: We have included this article as cancers of the digestive tract are frequent sites for metastasis or recurrence of oral cancers.

January, 2004|Archive|

Merger and new project boost UNLV tech hopes

  • 1/26/2004
  • Las Vegas
  • Valerie Miller
  • LasVegasPress.com

A merger between two conglomerates could mean big rewards for the University of Nevada, Las Vegas. Science & Engineering Technology (SEA), which is headquartered in New Orleans and works with UNLV, is being acquired by Washington, D.C.-based technology firm ITS Services. The $200 million deal announced last week may help propel groundbreaking research now being conducted between SEA and UNLV.

That work includes attempts to develop a new, quicker method for early detection and treatment of oral cancer. The SEA method — which is scheduled to be tested with the help of the soon-to-open UNLV Dental School — would involve the use of both multi-spectral imaging using light reflection and high-speed wireless data transmission. Ron Ryan, the vice president of SEA in Las Vegas says that use of multi-spectral imaging technology to diagnose oral cancer is already being tested by SEA with the U.S. Army. The military is interested in quicker methods for detecting cervical cancer in service women. The idea to study the application of the technology to detecting oral cancer actually was suggested by UNLV Provost Ray Alden a few years ago in a meeting, according to Ryan. That suggestion could really help UNLV and its dental school gain prominence as research facilities, SEA officials contend.

“We will help elevate them and help them reach their goal of being research and technology intensive,” Ryan says. ITS is all for the research, adds Ryan. “It was something we kind of [SEA] brought to the party and ITS liked. The merger with them strengthens our IT ability.”

Bobby Savoie, CEO of SEA, says that his company has about 20 jobs in Las Vegas. “We have no intention of cutting jobs in Las Vegas. We are looking to add jobs.” Prior to the merger, ITS had a little more than 400 employees, while SEA had about 500, according to ITS CEO Todd Stottlemyer. He says between the two companies there are about 100 job openings.

When it comes to research, SEA’s Savoie agrees that the partnering of SEA and UNLV is a win-win situation. “We feel it will be very positive in the creation of a technology center in Las Vegas,” he says of the cancer research project. The SEA chief also believes his company’s procedure for detecting cervical cancer can be adapted for use in oral cancer detection. “The fingerprint of cervical cancer is similar to the footprint of oral cancer,” Savoie explains. “We have a laser probe that identifies the cancer cells versus the healthy cells. What we are working on now is a grant to treat the cancer cells.” The cells must be hit with the right type of laser light, he adds, and thus the cells can be eliminated without the need for invasive surgical cutting. “If we could do this, the UNLV dental school would become world famous for this.” Basically, the spectrum of light shined on to soft tissue will reflect back differently is the cells are cancerous or potentially cancerous, Ryan says. Dentists could be trained in how to use this technology for early detection of oral cancer. “They are often the first ones in [a person’s mouth],” he notes. Ryan explains that SEA is putting together a federal grant proposal to seek research funding for the project from the U.S. Army for about a million dollars. That branch of the military could use the technology for screening and treatment of its service personnel deployed in remote locations, such as on the battlefield, he adds. The innovations UNLV is partnering with SEA to perfect could also be applied right here in Nevada, as well, in rural areas, Ryan says.

The wireless transmission of high-quality and data-rich images increases the value of the technology for use in rural areas, according to SEA. It is in such areas where good health care can often be difficult to come by, but the multi-spectral imaging device is planned to be portable. The image will be on a high-resolution, digital record and can be easily transmitted to a doctor anywhere to make a diagnosis, according to Ryan.

January, 2004|Archive|

Hyperbaric Oxygen Therapy for Radionecrosis of the Jaw: A Randomized, Placebo-Controlled, Double-Blind Trial From the ORN96 Study Group

  • 1/25/2004
  • Djillali Annane et al.
  • Journal of Clinical Oncology, 10.1200/JCO.2004.09.006

Purpose:
To determine the efficacy and safety of hyperbaric oxygen therapy (HBO) for overt mandibular osteoradionecrosis.

Patients and Methods:
This prospective, multicenter, randomized, double-blind, placebo-controlled trial was conducted at 12 university hospitals. Ambulatory adults with overt osteoradionecrosis of the mandible were assigned to receive 30 HBO exposures preoperatively at 2.4 absolute atmosphere for 90 minutes or a placebo, and 10 additional HBO dives postoperatively or a placebo. The main outcome measure was 1-year recovery rate from osteoradionecrosis. Secondary end points included time to treatment failure, time to pain relief, 1-year mortality rate, and treatment safety.

Results:
At the time of the second interim analysis, based on the triangular test, the study was stopped for potentially worse outcomes in the HBO arm. A total of 68 patients were enrolled and analyzed. At 1 year, six (19%) of 31 patients had recovered in the HBO arm and 12 (32%) of 37 in the placebo arm (relative risk = 0.60; 95% CI, 0.25 to 1.41; P = .23). Time to treatment failure (hazard ratio = 1.33; 95% CI, 0.68 to 2.60; P = .41) and time to pain relief (hazard ratio = 1.00; 95% CI, 0.52 to 1.89; P = .99) were similar between the two treatment arms.

Conclusion:
Patients with overt mandibular osteoradionecrosis did not benefit from hyperbaric oxygenation.

Authors:
Djillali Annane, Joël Depondt , Philippe Aubert , Maryvonne Villart , Pierre Géhanno , Philippe Gajdos , and Sylvie Chevret

Authors’ Affiliation:
From the Unité de Médecine Hyperbare and Service Pharmaceutique, Hôpital Raymond Poincaré, Garches; Service ORL et Chirurgie Cervico-Faciale Hôpital Bichat-Claude Bernard; and Département de Biostatistique et Informatique Médicale, Hôpital Saint Louis, Paris, France.

January, 2004|Archive|

Personal tragedy turned into warning against teen tobacco use

  • 1/23/2004
  • Carson, NV
  • Maggie O’Neill
  • Record-Courier

Students at Carson Valley Middle School listened — and listened well — as oral cancer survivor Gruen Von Behrens relayed a message on Wednesday. “I didn’t think it’d happen to me,” he said. Von Behrens, once a popular 17-year-old baseball player at an Illinois high school, stood as a 26-year-old advocate before middle school students, telling how tobacco took his good looks away. “I know I’m a little hard to understand, so you’re going to have to bear with me and listen,” he said to the packed auditorium. “This isn’t a mask I can take off and throw in the closet. I’m like this 365 days a year.” “This” began for Von Behrens when he was 17 and noticed a white spot on his tongue that began to grow and cause it to split. He told his mother the drooling she noticed was from a painful wisdom tooth. “I didn’t want my mom to see what was going on in my mouth,” he said. At the same time, he holed up in the bathroom, asking God why this was happening to him.

“This” began with chewing tobacco when he was 13, a decision he regrets 33 surgeries later. “I liked the way it tasted,” he said at the assembly. “It made me feel good.” Concerned about his wisdom tooth, Von Behrens’ mother took him to a dentist. Von Behrens told the dentist he wasn’t there due to a tooth. He had cancer. The dentist agreed. “I’ve never seen my mom cry like that,” Von Behrens said. “It ripped her heart out.” Doctors gave Von Behrens a 25 percent survival chance for his first surgery. The operation took 13 hours as friends and family gathered anxiously in a waiting room. “At 17, you’re not supposed to think about life and death issues,” he said. He did survive, but doctors severed his tongue as part of the operation. The 5-foot-10 baseball player recuperated a month and a half later to discover another face in the mirror. “I said, ‘Man this sucks. I’m not that good-looking guy anymore.'” Next came painful radiation and when he reached 19, a time he said should be “the best years of life,” doctors transplanted three inches of bone from his back to his face to give him a jaw. The transplant lasted two days. Then his body rejected it.

In February 2002, doctors cut bone from his left leg to again attempt to shape a jaw for Von Behrens. The surgery was a success, but left Von Behrens with a flattened calf and on crutches. None of “this” has stopped the courageous man, scheduled to undergo his 34th surgery March 10. None of it has stopped Von Behrens from making a passionate plea that people should not be judged on appearance. “Be your own person and be yourself,” he said at the assembly. “Friends don’t care what you look like. Talk to the person sitting next to you. They could (turn out to be) your best friend.” He spoke of the small things and of family and of friends who make life meaningful. “Be thankful for what you have guys and enjoy life. Be nice to your parents and nice to your friends. Tell them you love them.” He encouraged students to speak out and tell others who are smoking or using chew to stop, to tell them it smells, to say they won’t give them a kiss with a stinky mouth. “Take what I have told you to heart guys,” he said. “If you see someone using (tobacco), say ‘You’re going to look like (Von Behrens).'” Toward the end of his talk, he said he is thankful every day for one thing. He walked across the gymnasium floor. “I can still walk,” he said.

January, 2004|Archive|

OCF founder featured in NYU Nexus Magazine

  • 1/22/2004
  • New York, NY
  • New York University

OCF Founder Brian Hill was the subject of an article in Nexus, a publication of New York University. The Dean of the university’s dental school, Dr. Michael Alfano has been a supporter of the foundation’s efforts since the inception of OCF. Content of the article follows:

BECOME A MEMBER OF THE ORAL CANCER FOUNDATION

Late stage oral cancer patients have a significantly poorer survival rate than those who have their cancer caught early. Early detection of the disease can make a difference in whether or not a patient survives their encounter with cancer or not. Brian Hill was one of the lucky ones. As a late stage 3 survivor, he is acutely aware of the issues related to oral cancer and its early detection, and now works to bring that awareness to others. He has established The Oral Cancer Foundation, a national, non-profit organization designed to reduce suffering and save lives through early detection, education, research, advocacy, and support, an act which has led him to discover a new mission in life.

In 1993, Brian Hill was living the American dream. Still in his early 40s, he had recently sold the successful company he founded, Implant Support Systems, Inc., which designed, manufactured, and distributed dental implants, to Lifecore Biomedical, a firm specializing in synthetic body fluids and implantable devices. The sale left him financially secure, and with a lifestyle that he describes as being “on top of the world.”

But that American dream was cut short when a lump in his neck was diagnosed by his ENT as cancer. Worse, the primary cancer which was found in his mouth, had been there for some time, perhaps more than 18 months, and the lump was a metastasis. His cancer was being caught in an advanced stage. No obvious risk factors, no pain, no warning. What’s more, he believed that he was receiving excellent oral health care. Having worked in the industry, he was very dentally aware. He had been under the care of two different dentists during the previous 12 months, one for a check up and X-rays, the other to have a crown done on a lower molar. Two different hygienists had taken care of his six-month cleanings. But there was a problem: none had performed an oral cancer screening. If they had, the cancer wouldn’t have had time to grow as large as it did and to metastasize to his neck.

At the M.D. Anderson Cancer Center in Houston, where he was treated, Brian endured disfiguring surgery followed by painful radiation treatments, which caused the outside of his neck and his mouth to bleed and become openly raw and blistered. Because he could no longer eat or drink through his mouth, he lost 50 pounds. He became addicted to pain killers, and his immune system, beaten up by the therapies, made him a target for infections in his mouth and elsewhere.

After years of treatment, Brian’s cancer is in remission, but he is very aware that oral cancer commonly produces second, primary tumors, particularly in the first five years after treatment. “Armed with what I now know,” he says, “I’ll be looking for any signs of it, and it won’t go unnoticed like the first time.” Today Brian devotes 100 percent of his time to The Oral Cancer Foundation, striving to build a consensus among the dental and medical communities, the public, and corporations on the importance of routine oral cancer screenings. The foundation believes that an informed and involved dental community can significantly reduce both the death rate and the morbidity of this disease. Dean Alfano, who serves on The Oral Cancer Foundation’s Advisory Board, believes that as a survivor who has made oral cancer awareness, prevention, and early detection his personal crusade, Brian is indispensable to efforts to make the disease a major national health issue. Says Dean Alfano, “I encourage every alumnus and friend who reads this article to visit Brian’s Web site, at www.oralcancerfoundation.org and to become a member of The Oral Cancer Foundation.”

January, 2004|OCF In The News|

Iressa May Help Combat Oral Cancer

  • 1/15/2004
  • International Journal of Cancer, December 2003

The new drug Iressa, which is approved for treating a type of lung cancer, may also be useful for treating oral cancers, Japanese researchers report. The drug is an inhibitor of a molecule called the epidermal growth factor receptor (EGFR), which is overactive in several cancers. Lab experiments show that Iressa triples the susceptibility of oral cancer cells to radiation therapy, by blocking the tumor’s ability to repair DNA damage after such treatment. In fact, “this new treatment strategy with radiation in combination with an EGFR inhibitor may help overcome oral cancer without surgery,” lead researcher Dr. Satoru Shintani suggested.

Shintani and colleagues at Ehime University School of Medicine came to these conclusions following a series of experiments with human oral cancer cell lines. The study is reported in the International Journal of Cancer.

Radiation or Iressa alone slowed proliferation of the cancer cells, and a cooperative anti-proliferative effect was seen when radiation was followed by Iressa treatment. After radiation, Iressa had a strong inhibitory effect on mechanisms in the tumor cells that repair DNA damage, and the researchers suggest this may help account for its enhancement of radiotherapy. Furthermore, when tumors were grafted into mice, the radiation and Iressa combination “caused a striking decrease in tumor cell proliferation.”

Thus they conclude that Iressa owes its action to “multiple mechanisms that may involve antiproliferative growth inhibition and effects on DNA repair after exposure to radiation.”

January, 2004|Archive|

Cancer Death Rates Falling

  • 1/14/2004
  • Washington
  • Maggie Fox
  • Reuters News Service

Death rates continue to drop for the top three cancer killers in men — lung, colon and prostate — and for breast and colon cancer in women, according to the latest American Cancer Society statistics, published Wednesday.

But more U.S. women are dying from lung cancer, the annual report shows. And more people are dying of obesity-related cancers such as some types of liver and esophageal cancer. It estimates that 1.368 million Americans will be diagnosed with cancer in 2004, and 563,700 will die of it. This works out to 1,500 Americans a day. Colon cancer death rates fell to 20.8 per 100,000 people per year in the latest year available, 2000. That compares to 20.9 per 100,000 in 1999 and 22.6 in 1995. Breast cancer deaths fell from 30.6 per 100,000 in 1995 to 26.7 in 2000, the group said. Cancer has long been the second leading cause of death in the United States after heart disease, accounting for about a quarter of all deaths. The statistics show it is possible to avoid many cancers, said Dr. Michael Thun, the Society’s vice president of epidemiological and surveillance research.

“Cancer is not an inescapable fact of life,” Thun told reporters in a telephone briefing. Stopping smoking is one way to avoid cancer. The report estimates that tobacco use will cause 180,000 cancer deaths in 2004 — 160,000 of them from lung cancer. In women, the epidemic of deaths from lung cancer trails that of men by about 25 years. This matches the decrease in smoking rates — women started smoking later than men did and took up smoking even as men started to kick the habit. A third of cancers will be caused by lifestyle factors such as lack of exercise, poor nutrition including a high-fat diet low in fiber, fruits and vegetables and obesity. For instance, Thun said, about 20 percent of U.S. adults have a fatty liver from obesity, which can lead to chronic hepatitis. This in turn can lead to cancer and helps explain a rise in liver cancer incidence in the United States. Obesity can also lead to stomach and bile reflux, which can irritate the lower esophagus and also eventually cause cancer, Thun said.

But advances in screening technology mean more cancers are being caught early, when they are more easily cured. And treatments, including surgical techniques, drug and targeted radiation therapy, mean the five-year relative survival rate for all cancers combined has risen to 63 percent from 51 percent in 1976. Thun said it is important to look at cancer rates and not just overall numbers. And they must be adjusted for age to have any meaning. “Solid tumors are diseases of aging. The number of people who get cancer go up but when you look at the trends in the death rates … you see that there been a decrease in the death rate from all cancers combined in men …and a smaller decrease in women. There’s clear progress in reducing death rates.”

One piece of bad news is that disparities in cancer rates and survival continue to worsen, Thun said.”Since the early 1980s the differences in the death rate in colorectal cancer between black and white men has widened,” Thun said. He said the death rate has decreased markedly among white men, probably because of screening and early treatment, while the death rates in black men have not changed much. The same is true, on a smaller scale, for women, he added.

January, 2004|Archive|

BioAlliance Pharma Announces Preliminary Phase III Data On Miconazole Lauriad Bioadhesive Buccal Tablets For Local Treatment of Oropharyngeal Candidiasis in Head and Neck Cancer Patients Following Radiation Therapy

  • 1/4/2004
  • Paris, France
  • press release
  • Business Wire

BioAlliance Pharma, a biopharmaceutical company focused on the field of drug resistance, today announced significant positive results from its confirmatory Phase III pivotal study of the miconazole Lauriad(R) 50mg Bioadhesive Buccal Tablet. The results concerned the treatment of oropharyngeal candidiasis in head and neck cancer patients following radiotherapy. The study demonstrates the potential efficacy and safety of a new formulation of miconazole administered as a bioadhesive extended release buccal tablet. The tablet contained 10 times less active drug compared to the same drug applied in a topical gel for treatment of oropharyngeal candidiasis, an oral fungus commonly found in immuno-compromised patients, including HIV and cancer patients, diabetics and the elderly.

With the EU clinical program now completed, the results of this investigation together with a previously completed supportive Phase III study in HIV-positive patients will form the basis of a registration filing in the EU in early 2005. An IND to conduct a pivotal Phase III trial in HIV-positive patients with oropharyngeal candidiasis is on track for filing with the U.S. FDA, also in early 2005.

“The results from these studies are strongly indicative of the efficacy and safety of our once a day topical formulation of the miconazole extended release, bioadhesive buccal tablet for first line local treatment of oropharyngeal candidiasis,” said Dominique Costantini, M.D., president and CEO of BioAlliance Pharma. “These excellent results for one of BioAlliance’s key technologies are extremely encouraging in terms of the company’s future development.”

Phase III Study in Head & Neck Cancer Patients

The trial was a comparative, noninferiority study, including a blind evaluation of clinical results, conducted at 36 sites in Europe and North Africa. This study was an open-label, multi-center, randomized, and controlled Phase III study in 308 patients with head and neck cancer being treated by irradiation. The primary objective of the study was to evaluate the clinical efficacy of miconazole Lauriad(R) tablets on oropharyngeal candidiasis after 14 consecutive days of treatment.

In this study, miconazole Lauriad tablets were compared with miconazole gel, which is marketed in Europe for the treatment of oropharyngeal candidiasis. Miconazole gel was administered in the oral cavity (125 mg/4 times per day) for 14 days. Enrollment was completed in April 2004. Further analyses of the data are ongoing and will be submitted for presentation at an upcoming international scientific conference.

Phase III Study in HIV-Positive Patients

The company has previously reported results from a multi-center, open-label, non-comparative Phase III trial completed in August 2003 and designed to evaluate the efficacy and safety of the 50 mg miconazole Lauriad(R) bioadhesive buccal tablet in HIV-positive patients suffering from oropharyngeal candidiasis (13th International Symposium on HIV & Emerging Infectious Diseases, Toulon, France, June 2004; Annual Congress of the French Society of Medical Mycology, Montpellier, France, June 2004).

This study was originally planned to include 60 patients but was stopped under the protocol after reaching 25 patients, following a group-sequential response-adaptive design based on a success rate of 70%. The results showed 94.7% clinical efficacy following 14 days of treatment.

In the study of HIV-positive patients, oropharyngeal candidiasis was clinically documented and confirmed by fungal culture before inclusion. Patients were treated for 14 days and those who exhibited a clinical response were followed up to an additional month to evaluate the relapse rate. Primary efficacy was defined by a complete disappearance of oral lesions or decrease of more than 50% of lesion extension after 14 days of treatment (clinical response).

Miconazole Lauriad(R) showed a 94.7% clinical response (18 of 19 patients PP) after 14 days of treatment, with fungal eradication (negative fungal culture) seen in 31.6% of patients (6 of 19). The absence of plasma concentration of miconazole at day 7 of treatment demonstrates that miconazole Lauriad(R) acts only locally.

“The results of this study confirm the efficacy and safety of the miconazole Lauriad(R) 50 mg bioadhesive buccal tablet to treat oropharyngeal candidiasis in patients with a severe immuno-compromised status,” said Prof. Bertrand Dupont, Head of Infectious and Tropical Diseases, Necker Hospital, Paris, France, and coordinator of the HIV study. “This new formulation of miconazole may represent an effective therapeutic alternative to other topical products or systemic treatments and could improve patient compliance.”

About BioAlliance Pharma

BioAlliance Pharma is a privately held late stage biopharmaceutical company focused on drug resistance through development and commercialization of innovative therapeutics targeting markets in cancer, HIV, severe infections and supportive care. The company has two broad proprietary drug delivery platforms represented by the Lauriad(R) adhesive technology and the Transdrug(R) nanoparticle technology that provide multiple product opportunities. Together with a New Chemical Entities program focused on development of new drugs in oncology and HIV, the company is able to address worldwide markets in the EU, US, and Asia.

The company’s lead product within its adhesive technology program, the miconazole Lauriad(R) 50 mg Bioadhesive Buccal Tablet, is being investigated in two recently completed Phase III trials in Europe for treatment of oropharyngeal candidiasis in cancer and HIV patients. A Phase I/II trial in hepatocellular carcinoma utilizing the company’s doxorubicin Transdrug(R) nanoparticle delivery technology is ongoing in Europe, where it has been granted an orphan medicinal product designation by the EMEA.

January, 2004|Archive|