Monthly Archives: November 2009

Advances in radiation therapy enable doctors to improve the quality of treatments for patients with head and neck cancer

Author: press release

Noted clinical experts detail recent developments at the annual ASTRO meeting in Chicago

Clinical studies suggest that advanced treatments like intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) are enabling radiation oncologists to enhance post-treatment health-related quality of life for patients with head and neck cancer.

In an educational session for radiotherapy professionals, delivered by two noted experts during the annual meeting of the American Society for Radiation Oncology (ASTRO) in Chicago last week, Avraham Eisbruch, M.D., professor at the University of Michigan, discussed how careful implementation of IMRT in the treatment of head and neck cancer can achieve high tumor control rates while minimizing xerostomia, a dry mouth condition that occurs when salivary glands are damaged.

Citing a new report summarizing results from RTOG 0022, a multi-institutional study comparing IMRT with earlier forms of treatment for head and neck cancer, Dr. Eisbruch said that IMRT for head and neck cancer achieved important goals in reducing treatment toxicity, notably xerostomia, and in yielding a high tumor control rate of 90%.(1)

For patients enrolled in the study and treated with IMRT, only 55% experienced Grade 2 or worse xerostomia at six months after treatment, as compared with 84% of patients treated with earlier forms of radiotherapy — a reduction of 35%. For the IMRT group, the percentage of patients with Grade 2 or worse xerostomia decreased steadily, to 25% at 12 months and 16% at 24 months. “This kind of improvement over time is not something we had been seeing with conventional forms of radiotherapy,(2)” said Dr. Eisbruch, who served as chair of RTOG 0022.

“Also, emerging data is suggesting that we can get improvements in broader aspects of post-treatment quality of life by using IMRT, beyond reducing xerostomia,” Eisbruch said. “Several studies comparing IMRT with conventional radiotherapy found that the IMRT patients did better not just in terms of dry mouth, but also other quality of life dimensions, including swallowing and nutrition.”(3)(4)(5)

According to Eisbruch, RTOG 0225, another multi-institutional study looked at IMRT with or without chemotherapy for head and neck cancer, and also reached positive conclusions. “That group reproduced the excellent results that individual treatment centers had been reporting, namely, a 90% loco-regional progression-free survival with minimal grade 3 and no grade 4 xerostomia.”(6)

IMRT involves shaping radiotherapy treatment beams so that they deliver a dose pattern that matches the size and shape of a targeted tumor while minimizing exposure of surrounding healthy tissues and organs. This approach has been widely adopted by radiation oncologists for the treatment of diverse forms of cancer. Ongoing clinical studies are now maturing, allowing long term outcomes to be assessed and validating IMRT based on clinical data.

Improving IMRT Through Image-Guidance
Lei Dong, PhD, associate professor of medical physics at the MD Anderson Cancer Center in Houston, Texas, detailed how new image-guidance technologies further enhance the accuracy of IMRT treatments by enabling clinicians to correct for patient set-up uncertainties and anatomical changes over a course of treatment.

“Clinicians naturally want to take advantage of the more conformal dose distributions that IMRT makes possible by reducing the treatment margins around a tumor, to protect more healthy tissues,” said Dr. Dong. “When we do that, it is important to ensure that the treatments are targeted very precisely, so the tumor receives the high dose treatments, and the dose to surrounding tissues and organs is kept as low as possible.”

Dr. Dong discussed the issue of basing radiotherapy treatment plans on single CT scans taken during treatment simulation. “Internal motion can affect the accuracy of tumor definition if the CT scan is acquired while the patient is swallowing,” he said, referencing a study he worked on with colleagues from M. D. Anderson Cancer Center.(7)

According to Dr. Dong, stereoscopic X-ray imaging and volumetric cone-beam CT imaging, two imaging techniques enabled by Varian’s On-Board Imager® kV imaging device, make it possible to fine-tune patient positioning just prior to each daily treatment. In addition, frequent imaging can alert clinicians to changes in a patient’s anatomy over time, so that a new treatment plan can be developed part-way through a course of treatment whenever warranted–a process called adaptive radiotherapy.

“Preliminary studies have shown that combining IGRT and adaptive IMRT replanning can improve the overall quality of the treatment plan and, most importantly, reduce unnecessary doses to normal organs surrounding the tumor, such as the parotid glands and oral cavities,” Dr. Dong said.(8) “Combining IGRT with IMRT creates a powerful tool for high precision radiation therapy.”

November, 2009|Oral Cancer News|

U.S. smoking rates remain steady, but vary widely by state

Source: Medical News
Author: John Gever

National rates of cigarette smoking showed little change in 2008 from a year earlier, the CDC reported, though states vary widely both in rates of current smoking and exposures of nonsmokers to secondhand smoke.

Some 20.6% of Americans were current smokers in 2008 (95% CI 19.9% to 21.4%), not significantly different from the 19.8% found in 2007 (95% CI 19.0% to 20.6%) according to the the government’s ongoing National Health Interview Survey, detailed by Shanta R. Dube, PhD, and other CDC researchers in the Nov. 13 issue ofMorbidity and Mortality Weekly Report.

But analysis of a another data set in MMWR — the 2008 results from the Behavioral Risk Factor Surveillance System (BRFSS) — revealed a twofold variation in rates among states.

Utah had by far the lowest rate of current cigarette smoking, at 9.2%, followed by California (14.0%), New Jersey (14.8%) and Maryland (14.9%), according to Ann M. Malarcher, PhD, and CDC colleagues.

West Virginia led the other end of the list at 26.6%. Other states with current smoking rates of 25% or more included Indiana, Kentucky, and Missouri.

West Virginia had several other smoking distinctions.

It was the only state in which the current smoking rate was higher among women than men — 27.1% versus 26.1% — although the difference was not statistically significant.

The BRFSS data showed the Mountain State had the highest rate of home exposure to secondhand smoke among 12 states and territories for which data were available.

Some 10.6% of West Virginia adults said there was secondhand smoke in their homes (95% CI 9.2% to 12.0%), while the lowest rate was in Arizona (3.2%, 95% CI 2.3% to 4.1%). The national median was 7.8%

West Virginia respondents were also least likely to report that smoking was banned inside their homes, at 68.8% (95% CI 67.0% to 70.6%).

The U.S. Virgin Islands sported the highest home smoking ban figure, 85.7% (95% CI 83.8% to 87.6%), a statistical tie with Arizona’s 85.6%. The national median was 78.1%.

Similar variation in workplace exposure to secondhand smoke was apparent in the result, though with a different pattern of highs and lows.

Tennessee had the lowest rate, with 6.0% of survey respondents saying there was secondhand smoke at work (95% CI 4.0% to 8.0%). Mississippi had the highest, at 15.8% (95% CI 13.7% to 17.9%). The national median was 8.6%.

As in previous surveys, the 2008 National Health Interview data showed that smoking rates were markedly higher among individuals with a high school education or less (27.5%, 95% CI 25.5% to 29.6%) compared with those with more education.

People with “some college” had a 2008 smoking rate of 22.7% (95% CI 21.3% to 24.2%) while just 5.7% of those holding graduate degrees were current smokers (95% CI 4.6% to 7.1%).

Dube and colleagues also found substantial racial-ethnic differences in 2008 smoking rates, similar to those seen in previous years:

  • Non-Hispanic whites: 22.0%
  • Non-Hispanic blacks: 21.3%
  • Hispanics: 15.8%
  • American Indian/Alaska native: 32.4%
  • Asian: 9.9%

In an unsigned commentary, MMWR editors noted that the national prevalence of smoking has declined significantly since 1998, when 24.1% of adults smoked. That was the year when the “master settlement agreement” with tobacco companies began limiting their marketing activities, the editors said.

But year-to-year decreases have been sporadic, they added.

“Although comprehensive tobacco control programs have been effective in decreasing tobacco use in the U.S., they remain underfunded,” the editors wrote.

The editors added that state-level tobacco control programs “need to continue to encourage the public to make their homes smoke-free.”

More states also need to legislate smoking bans in restaurants, bars, and other workplaces, they said, as the patchwork nature of such bans appears to be a major factor in the state-to-state variation in exposure to secondhand smoke on the job.

No external funding for the CDC studies was reported.

No potential conflicts of interest were reported.

November, 2009|Oral Cancer News|

Brachial plexus injury may be underreported following radiation therapy in patients with head and neck cancer

Author: John Otrompke

Radiation therapy for head and neck cancer may cause an injury to the brachial plexus nerve network in as many as 20% of patients, researchers stated here at the American Society of Therapeutic Radiology and Oncology (ASTRO) 51st Annual Meeting. The incidence of the condition, characterised by numbness in the arms, inability to use the shoulder, and/or atrophy or retraction of chest muscles, may be underreported, suggesting that healthcare providers devise an avoidance strategy when administering high-dose radiation.

“This was the first study that looked at brachial plexus injury and quality-of-life effects in patients for head and neck cancer, because in the past these patients never survived long enough for physicians to notice the symptoms, which include chronic frost-bite sensation in the fingers,” said Allen M. Chen, MD, Department of Radiation Oncology, University of California Davis Health System, Sacramento, California, on November 3.

The study was originally conceived based on clinical observations, he said. “We would see these patients coming in with these odd symptoms all the time, and we couldn’t explain why.”

The study looked at 196 patients, without prior symptoms of brachial plexopathy, who returned for follow-up after high-dose radiation for head and neck cancer and completed a questionnaire designed to look for symptoms of the injury to brachial plexus, a nerve complex in the arm, chest, and shoulder. Symptoms included pain, numbness and tingling, or motor weakness.

Of the patients, 20 (10%) scored positive for injury, with the median onset of the condition occurring 20 months after completion of the radiation. The median time interval between radiation and completion of the questionnaire was 35 months.

“Among long-term survivors, prevalence could be in the ballpark of 15% to 20%,” Dr. Chen said.

Of those patients who developed brachial plexopathy, 80% received more than 1 dose of 70 gray or more to more than 5% of the brachial plexus, and all of them received a dose of 66 gray or higher to at least 5% of the brachial plexus.

Of the patients, 112 (57%) received surgery with postoperative radiation, while 84 (43%) received definitive radiation alone. Additionally, 72 patients (37%) received concurrent chemotherapy.

“It is impossible to blame all these cases on radiation alone, because confounding factors, such as chemotherapy, surgery, osteoarthritis, or occupational hazards, could have contributed to the condition,” said Dr. Chen, adding that groups such as the Radiation Therapy Oncology Group have designed a computer atlas of the brachial plexus to enable avoidance strategies, especially because the nerve complex is difficult to see on a computed tomography scan.

1. presented at ASTRO
2. presentation title: Brachial Plexopathy After Radiation Therapy for Head-and-Neck Cancer. Abstract 65

November, 2009|Oral Cancer News|

Chemo treatments lengthen lives for head, neck cancer patients

Author: Brendan Missett

Patients with head and neck cancer receiving a combined treatment of chemotherapy and radiation may live 2.1 years longer than those treated only with radiotherapy, new research suggests.

The study, published in the October 27 issue of The Lancet Oncology, separated 966 patients with advanced head and neck cancer into four treatment groups, and examined their progression over 10 years, HealthDay News reports. The four groups designated patients who received radiotherapy alone, two courses of simultaneous chemotherapy and radiotherapy, two courses of chemotherapy after completing radiotherapy, and chemotherapy both during, and after radiotherapy.

Researchers found that chemo, given at the same time as radiotherapy, was most effective in reducing deaths and cancer recurrence in head and neck cancer patients who hadn’t undergone surgery. Chemotherapy given after radiotherapy was completely ineffective, according to the study.

The UK Head and Neck Cancer Group researchers wrote that chemotherapy drugs offer an “inexpensive” method to “considerably improve the likelihood of completing treatment, essential for improving the chances of a cure.”

According to the American Cancer Society, more than 1,500 people in the U.S. are expected to die of cancer each day in the next year. Doctors recommend an array of imaging tests or lab tests to detect some types of cancer while they are treatable.

November, 2009|Oral Cancer News|

Access Pharmaceuticals provides update on MuGard commercial launch in North America

Author: press release

Access Pharmaceuticals, Inc., today provided an update on its North American commercial launch of MuGard, an FDA approved treatment for oral mucositis, a debilitating side effect of radiation treatment and chemotherapy. Access intends to commercially launch MuGard in North America in the first quarter of 2010. Key strategic items pertaining to the launch include:

Access is currently working with its contract liquid manufacturer, Accupac, on initial clinical and stability batches, and expects to have initial commercial quantities available in 1Q 2010.

Access is working with outside regulatory consultants in developing and finalizing its reimbursement strategy as it pertains to third-party payors and Medicare/Medicaid.

Consistent with strategies employed by its global marketing partners, Access is working with key opinion leaders to develop a strategy for post-approval studies if and as needed. Access believes that its approved label indication and directions for use supports positioning MuGard as a preventative for oral mucositis caused by radiation and chemotherapy treatments, and provides for expansion into treatment of all types of oral wounds including aphthous ulcers, canker sores and traumatic ulcers, such as those caused by oral surgery.

Access has signed a deal with iMedicor to support online eMarketing efforts and education of oncologists, radiation oncologist and support staff as it pertains to oral mucositis and MuGard specifically. Access intends to build a hybrid, dedicated salesforce with oncology supportive care experience.
Co-Promotion: Access continues to seek potential co-promotion arrangements with pharmaceutical and biotechnology companies in the oncology and oncology supportive care fields. Access believes that it can reach a targeted radiation oncologist community while still seeking broader distribution relationships.

“Access is on track for an early 2010 commercial launch of MuGard, and we look forward to bringing this important oncology supportive care treatment to the US market,” stated Frank Jacobucci, a consultant to Access, and previously CEO of Milestone Biosciences. “With the launch of MuGard, we believe clinicians will have a welcome addition to their oncology supportive care arsenal, filling a significant unmet medical need for a treatment of oral mucositis. I have always known the substantial potential for MuGard in the prevention and treatment of oral mucositis, as well as an exciting commercial opportunity in the pharma sector.” Mr. Jacobucci has over 20 years experience in sales management, including senior sales executive positions at oncology focused companies including MGI Pharma, Genetics Institute, Wyeth Oncology, Aventis, Precision Therapeutics and CRC Oncology Services.

MuGard is a novel, ready-to-use mucoadhesive oral wound rinse for the management of oral mucositis, a debilitating side effect of many anticancer treatments. Up to 80% of all patients receiving radiotherapy and approximately 40% of all chemotherapy patients develop oral mucositis, and almost all patients receiving radiotherapy for head and neck cancer and those undergoing stem cell transplantation develop mucositis. The market for the treatment of oral mucositis, expanding to include all patients undergoing chemotherapy and radiotherapy, is estimated to be in excess of $5 billion world-wide. MuGard forms a protective coating over the oral mucosa when swirled gently around the mouth. In a comparison of cancer patients receiving standard mucositis care with those patients receiving MuGard, the incidence and severity of mucositis was significantly lower in the MuGard treated group using a validated scale for the assessment of oral mucositis.

MuGard is commercially launched by Access’ partner, SpePharm, in five European countries, having been granted the CE mark certification in October 2008 with the labeling “prevention and management of the lesions and symptoms of oral mucositis.” SpePharm is currently gathering feedback from clinicians in the UK, Germany and Italy that are participating in a patient assessment project. SpePharm expects that out of a total of approximately 1500 to 2000 patients who will be assessed in this project, a subset of patient forms will be collected by year end, and aggregated clinician and patient feedback will continue to be available on a rolling basis during the fourth quarter 2009 and 2010. Introduction of MuGard into France, Central and Eastern Europe, the Benelux countries and the rest of Europe is anticipated over the next 12 to 18 months.

About Access:
Access Pharmaceuticals, Inc. is an emerging biopharmaceutical company that develops and commercializes propriety products for the treatment and supportive care of cancer patients. Access’ products include ProLindac(TM), currently in Phase 2 clinical testing of patients with ovarian cancer, and MuGard(TM) for the management of patients with mucositis. The company also has other advanced drug delivery technologies including Cobalamin(TM)-mediated targeted delivery and oral drug delivery, its proprietary nanopolymer delivery technology based on the natural vitamin B12 uptake mechanism and Thiarabine, a new generation nucleoside analog which has demonstrated both pre-clinical and clinical activity in certain cancers.

November, 2009|Oral Cancer News|

National Comprehensive Cancer Network receives research grant to evaluate pralatrexate in solid tumors and hematologic malignancies

Author: PRNewswire press release

The National Comprehensive Cancer Network (NCCN) has been awarded a research grant from Allos Therapeutics, Inc. to support clinical studies of pralatrexate (FOLOTYN(TM), Allos Therapeutics, Inc.) in the treatment of select hematologic malignancies and solid tumors.

Pralatrexate was recently approved by the FDA to treat patients with relapsed or refractory peripheral T-cell lymphoma, a type of non-Hodgkin’s lymphoma that is relatively uncommon, but particularly aggressive. Clinical trials supported by this grant will focus on evaluating innovative single agent and combination studies of pralatrexate in Burkitt’s lymphoma, multiple myeloma, specific indolent lymphomas, ovarian cancer, head and neck cancer, prostate cancer, gastroesophageal cancer, and colorectal cancer.

“NCCN is committed to enhancing cancer care by evaluating new agents such as pralatrexate to determine their full potential in treating several types of cancer,” says William T. McGivney, Ph.D., Chief Executive Officer, NCCN. “Through this research grant from Allos Therapeutics, Inc., we are pleased to provide NCCN Member Institutions with an opportunity to take part in innovative cancer research with the hope that their work will ultimately benefit patients with cancer.”

Pralatrexate is a chemotherapy drug classified as an antifolate that works by interfering with the ability of cancer cells to divide, resulting in cell death. It is a targeted therapy that is designed to accumulate preferentially in cancer cells.

“Our collaboration represents a unique opportunity to benefit from the research expertise of NCCN and the NCCN Member Institutions, as we explore the potential of investigator initiated clinical studies of FOLOTYN,” said Paul L. Berns, President and Chief Executive Officer at Allos Therapeutics, Inc. “We are pleased to support an organization that shares our commitment to innovative cancer research.”

The NCCN Oncology Research Program (ORP) facilitates all phases of clinical research by identifying clinical investigators and initiating trials at NCCN Member Institutions. The NCCN ORP draws on the expertise of investigators at 21 of the world’s leading cancer centers and establishes collaborations with pharmaceutical and biotech companies in order to advance therapeutic options for patients with cancer. To date, the NCCN ORP has provided more than $20 million in research funding to investigators at NCCN Member Institutions.

November, 2009|Oral Cancer News|

Intensity-modulated radiation offers treatment advantages over conventional therapy for head and neck cancer

Author: John Otrompke

Patients treated with simultaneously integrated boost treatment using intensity-modulated radiation therapy (IMRT) experience better overall survival, disease-free survival, and local recurrence rates, as well as decreased dermatitis and better postoperative salivary function that those treated with conventional radiation.

“IMRT treatment was described as ‘boosted’ because we use 2 different doses in the same patient, who gets a dose of 2.12 gy to 1 part of their anatomy, while another part gets 1.8 gy,” said Sebastien Clavel, MD, University of Montreal, Montreal, Quebec, on November 3 at the American Society of Therapeutic Radiology and Oncology (ASTRO) 51st Annual Meeting.

In the study, 249 patients with stage III and IV oropharyngeal carcinoma were treated between 2000 and 2007. Of these, 100 received IMRT, while 149 patients received conventional radiation therapy.

After a 33-month median follow-up, 95.4% of those treated with IMRT were still alive, compared with 75.8% of those in the conventional arm. Disease-free survival was 89.3% for the IMRT group, compared with 71.6% in the conventional radiation arm. In addition, local control was 92.4% in the IMRT patients, compared with 85.3% in the conventional group.

“With the old technique, the rays were shooting from both sides, whereas with IMRT, the rays come from all directions,” said Dr. Clavel. “When using IMRT, we also always give them a 3-mm margin with the skin, both of which result in fewer cases of dermatitis.” IMRT patients experienced a 20% decrease in dermatitis grades 3 and 4.

“If we are able to treat the tumour with IMRT while avoiding the structure of the parotid gland, which produces saliva, the patients can live better, because more saliva is useful to protect the teeth, to eat, and swallow,” he added, noting that only 8% of those treated with IMRT experience grade 3 or 4 xerostomia at 2 years following treatment, compared with 80% of those treated with conventional radiation.

Better salivary function was also associated with increased weight regain post operatively. “Patients lost 10% of their weight during treatment; while they did not gain all their weight back in the IMRT group, they were able to regain up to 50% more than those treated with conventional radiation,” said Dr. Clavel.

1. presented at American Society of Therapeutic Radiology and Oncology (ASTRO)
2. presentation title: A Comparison of Simultaneously Integrated Boost Using Intensity-Modulated Radiation Therapy and Conventional Radiation Therapy in the Setting of Concomitant Carboplatin and 5-Fluorouracil for Locally Advanced Oropharyngeal Carcinoma. Abstract 69

November, 2009|Oral Cancer News|

Weekly radiation of more than 10 gy improves local control in head and neck cancer patients

Author: John Otrompke

Patients with head and neck squamous cell carcinoma who receive an average weekly fractionated radiation dose of more than 10 gy experience significantly better local control at 2 years, unless they are receiving chemotherapy at the same time, according to a study presented here at the American Society of Therapeutic Radiology and Oncology (ASTRO) 51st Annual Meeting.

“We’re not seeing the benefit in those who also receive chemotherapy with the radiation,” said Alek F. Dragovic, MD, Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama. If they have low-stage cancer, they may not necessarily need chemotherapy along with radiation. Also, patients are often not healthy enough to receive chemotherapy if they can’t tolerate the side effects, Dr. Dragovic explained in his presentation on November 3.

In the study, 601 patients who received definitive radiotherapy were divided retrospectively into those who received more or less than an average weekly dose of 10 gy.

Patients who received the traditional schedule of once per day made up 45.1% of the patient population, those who received concomitant boost radiation, in which patients get treated twice per day during the last 2 weeks of radiotherapy, were 17.6% of the population; while 17.5% were treated with simultaneous integrated boost, 15.1% received radiation twice daily, and other received other schedules.

Overall, patients who received on average more than 10 gy per week experienced 77.4% local regional control at 2 years, compared with 71.4% who received less than 10 gy per week. For those who received no chemotherapy, however, average weekly dose of more than 10 gy was associated with 80.9% local regional control at 2 years, compared with 60.9% for those who received less.

But for those patients who also received chemotherapy, on the other hand, the numbers were 77.3% and 75.3%, respectively, and the results were not statistically significant,

Additionally, for those treated with concurrent chemotherapy, severe late dysphagia (including difficulty swallowing, scarring of the oesophagus, and dependence on a stomach tube) was found in 38.4% of those who received more than 10 gy per week, compared with 32% of those who received less.

“Those who received the higher dose per week also had more acute toxicity, such as oral ulcers and mucositis, but long-term toxicity does not end up being increased,” concluded Dr. Dragovic.

1. presented at Presented at ASTRO
2. Presentation title: The Importance of Average Weekly Dose in Patients With Head-and-Neck Cancer Treated With Definitive Radiotherapy. Abstract 66

November, 2009|Oral Cancer News|

HPV vaccine clears viral infection and may reduce cancerous lesions

Author: staff

Breakthrough study reports complete and partial remissions following vaccination

A new vaccine designed to stimulate an immune response against a cancer-causing human papillomavirus (HPV-16) can eliminate chronic infection by the virus and may cause regression of precancerous genital lesions in women who receive the vaccine.

According to a report published in the November 5 issue of the New England Journal of Medicine (2009;361:1838-47), the vaccine successfully induced HPV-specific immune responses in 100% of patients with advanced vulvar intraepithelial neoplasia (VIN3), a life-threatening disease that in the majority of cases results from HPV infection and for which there is as yet no satisfactory standard therapy.

Among the women who participated in the study, the majority (79%) experienced measurable regression of their VIN3 lesions within 1 year of vaccination. Nine of the women (47%) experienced complete disappearance of lesions and were still symptom-free two years following vaccination. The virus was undetectable in four of five women whose disease had regressed completely after the first year.

According to researchers who conducted the phase II study at the Leiden University Medical Center in Leiden, The Netherlands, spontaneous regression of HPV-16 positive VIN3 lesions is very rare, occurring in less than 1.5% of patients. The induction of HPV-specific T-cell immune responses following vaccination, and the researchers’ observation that stronger vaccine-induced immune responses correlated with better clinical outcome indicate that the vaccine is the most likely cause of the high response rate among the patients treated in the study.

Unlike recently approved vaccines that prevent against infection by HPV, such as Merck’s Gardasil® and GlaxoSmithKline’s Cervarix®, this is a therapeutic HPV vaccine for people who have already been exposed to HPV and who are unable to clear the virus on their own and are at high risk of developing HPV-related cancer.

The vaccine is composed of HPV synthetic long peptides (SLP®), a proprietary technology developed by Dr. Cornelis Melief and others at Leiden University in The Netherlands in partnership with ISA Pharmaceuticals. In recognition of this and his other important contributions to the development of immune-based therapies for cancer, Dr. Melief received in June of this year the 2009 William B. Coley Award for Distinguished Research in Tumor Immunology from the Cancer Research Institute (CRI), a nonprofit organization based in the United States dedicated exclusively to harnessing the power of the immune system to treat, control, and prevent cancer.

To accelerate the testing and refinement of synthetic long peptides in the treatment of cancers that are not of viral origin, the Cancer Research Institute awarded Dr. Melief a grant of $300,000 for the establishment of a Good Manufacturing Practice (GMP) facility at Leiden University. The facility will produce clinic-grade synthetic long peptides for use in clinical trials within the Cancer Vaccine Collaborative (CVC), a joint program of the Cancer Research Institute and the Ludwig Institute for Cancer Research Ltd (LICR) in 2009.

The CVC is a global network of academic clinical trial sites and immune monitoring laboratories that is carrying out a coordinated program of early stage trials of therapeutic cancer vaccines. To date, the CVC has conducted more than 40 trials of various combinations of therapeutic vaccines targeting highly immunogenic cancer antigens, chiefly the NY-ESO-1 antigen. NY-ESO-1 is a prototypic member of the cancer-testis (CT) family of antigens, which are expressed in cancer but not normal adult tissue. In a recent publication, the National Cancer Institute prioritized this antigen among the top 10 most promising cancer immunotherapy targets available. NY-ESO-1 has been the central focus of CVC and other CRI or LICR sponsored studies for more than a decade.

Dr. Melief will supply CVC investigators with synthetic long peptides derived from XAGE antigens, which have properties similar to other CT antigens including NY-ESO-1. XAGE antigens are expressed in a number of cancers, particularly adenocarcinoma of the lung. CVC investigators will test the efficacy of delivering XAGE in the form of synthetic long peptide as compared to vaccines that deliver XAGE in the form of whole protein or DNA.

Upon completion of the GMP upgrade to Leiden University’s synthetic long peptide production facility, it will be the second of two academically funded and operated bioproduction facilities within the CVC network. The first, at Cornell University in Ithaca, New York, recently completed production of clinic-grade recombinant NY-ESO-1 protein for CVC trials in melanoma and ovarian cancer, and is now producing clinic grade Melan-A/MART-1 protein for CVC clinical trials.

About vulva epithelial neoplasia
An epithelial neoplasia occurs when cells lining the outer layers of the body (for instance the skin and inside the mouth, intestines and the genitalia) start dividing and growing in an unusual way. An epithelial neoplasia can manifest itself as a wart or a lump, and in some cases it can develop into cancer, if left untreated. A majority of epithelial neoplasias of the vulva (the outer parts of the female genitalia) are caused by an infection of human papilloma virus type 16. Symptoms of the disease include discomfort, itching, irritation, pain and local bleeding. Epithelial neoplasia of the vulva is chronically debilitating and life-threatening due to the associated symptoms and the high risk of developing invasive cancer. (Source: ISA Pharmaceuticals)

About the CRI/LICR Cancer Vaccine Collaborative
The Cancer Vaccine Collaborative is a partnership between two not-for-profit institutions, the Cancer Research Institute (CRI) and the Ludwig Institute for Cancer Research (LICR). Each of these institutions has a long and distinguished history in the field of cancer immunology and each is committed to translating laboratory discoveries in this field into therapeutic cancer vaccines. Begun in 2001, the CRI/LICR Cancer Vaccine Collaborative supports and coordinates a network of early phase cancer vaccine trials at nineteen hospitals and medical centers around the world. Driven by a scientific agenda, these parallel, single-variable trials use defined antigens, standard treatment protocols, uniform monitoring methodologies, and centralized data collection to provide comparable results that are teaching us how to effectively immunize against cancer.

About the Cancer Research Institute
The Cancer Research Institute (CRI) is the world’s only non-profit organization dedicated exclusively to the support and coordination of scientific and clinical efforts that will lead to the immunological treatment, control, and prevention of cancer. Guided by a world-renowned Scientific Advisory Council that includes four Nobel Prize winners and twenty-nine members of the National Academy of Sciences, CRI supports leading-edge cancer research at top medical centers and universities throughout the world. The Cancer Research Institute is ushering in a new era of scientific progress, hastening the discovery of effective cancer vaccines and other immune-based therapies that are providing new hope to cancer patients.

The Cancer Research Institute has one of the lowest overhead expense ratios among non-profit organizations, with more than 85 percent of its resources going directly to the support of its science, medical, and research programs. CRI meets or exceeds all 20 standards of the Better Business Bureau Wise Giving Alliance, the most comprehensive U.S. charity evaluation service, and according to Charity Navigator exceeds or meets industry standards and performs as well as or better than most cancer charities. CRI has also received an ‘A’ grade for fiscal disclosure and efficiency from the American Institute of Philanthropy as well as top accolades from other charity watchdog organizations. For more information, visit

November, 2009|Oral Cancer News|

Report highlights cancer advances

Author: Charles Bankhead, Staff Writer, MedPage Today

As the war on cancer enters its fifth decade, 51 studies stood out as examples of progress that occurred in the past year, as determined by the American Society of Clinical Oncology (ASCO) and reported in “Clinical Cancer Advances 2009.”

Reflecting input from specialists throughout the field, the ASCO annual report highlights research developments for nine types of cancer, as well as cancer disparities, quality of life and quality of care, and cancer prevention and screening.

“As this report demonstrates — and as history shows — investment in clinical cancer research pays off,” ASCO president Douglas Blayney, MD, of the University of Michigan in Ann Arbor, said in a statement included in the report.

“Since 1990, cancer mortality rates have declined by 15%. Today, two-thirds of patients survive at least five years after diagnosis, compared to just half of patients 40 years ago.”

“Thanks to basic research advances, we are entering an era of personalized cancer medicine, in which treatment is tailored to the unique genetics of the individual,” Blayney added.

The entire report appears online in the Journal of Clinical Oncology, but here is a summary of developments related to some of the most common cancers.

In an attempt to provide context and a diversity of viewpoints, MedPage Today, in collaboration with ABC News, solicited comments from cancer specialists who were not involved in developing the ASCO publication. As appropriate, their views are included with the review of cancer research highlights.

Head and Neck Cancers
Adding the targeted agent cetuximab (Erbitux) to chemotherapy significantly improved progression-free survival and overall survival in patients with untreated recurrent or metastatic head and neck cancer. Noting failure of several previous trials to demonstrate a survival advantage with chemotherapy, ASCO cancer specialists said the findings should change clinical practice.

Another targeted agent, gefitinib (Iressa), did not improve survival compared with methotrexate in patients with recurrent squamous-cell carcinoma of the head and neck.

The practice of “re-irradiation” following chemoradiation therapy reduced the risk of local recurrence but did not improve survival in patients with adverse-feature head and neck cancer. Additional radiation reduced the risk of recurrence by 50%, but patients did not live any longer than those who received conventional chemoradiation followed by active surveillance. Moreover, re-irradiation led to a fourfold increase in the incidence of grade 3-4 toxicity.

Breast Cancer
Results of a large, randomized clinical trial settled a longstanding debate about the superiority of a standard three-drug chemotherapy regimen versus monotherapy with capecitabine (Xeloda) for breast cancer in women 65 and older. Women randomized to the single agent had a twofold increase in the risk of relapse and death compared with women who received cyclophosphamide, methotrexate/fluorouracil, and doxorubicin. Three-year relapse-free survival was 68% with monotherapy and 85% with the combination. Overall survival was 86% with monotherapy versus 91% with the combination.

Stefan Gluck, MD, of the University of Miami, had a different take on the study results. Acknowledging the better survival in the capecitabine arm, Gluck took issue with the trial’s clinical significance. “This is not major research. It did not change practice, did not change outcome, did not change toxicity, and did not change cost.”

On the other hand, Hyman Muss, MD, of the University of North Carolina in Chapel Hill, cited the trial results as an example of clinical research that has influenced his clinical practice in the past year.

Two studies provided evidence that the investigational class of agents known as poly(ADP-ribose) polymerase (PARP) inhibitors has efficacy in so-called triple-negative breast cancer. The agents block cancer cells’ ability to repair DNA damage, including damage inflicted by chemotherapy.

Seconding the ASCO specialists’ view, Gluck said the investigation of PARP inhibitors is a major accomplishment in the field of breast cancer.

Michael J. Fisch, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, agreed, calling PARP inhibitors “a new category of treatment for a very difficult-to-treat subset” of breast cancer patients.

Gastrointestinal Cancers
A large Phase III clinical trial of patients with HER2-positive gastric cancer had a significant reduction in the risk of death when treated with trastuzumab (Herceptin) plus standard chemotherapy compared with chemotherapy alone. Treatment with trastuzumab did not increase the risk of symptomatic congestive heart failure.

British investigators reported data from a trial that established the first standard of care for biliary tract cancer. The combination of gemcitabine (Gemzar) and cisplatin significantly improved progression-free survival and overall survival compared with gemcitabine alone.

Adding the targeted agent bevacizumab (Avastin) to standard chemotherapy did not reduce the risk of recurrence in early-stage colon cancer. The three-year disease-free survival was 77.4% with the investigational therapy and 75.5% with standard chemotherapy.

M.D. Anderson’s Fisch said oncologists had mixed reactions to the bevacizumab findings.

“On one hand, oncologists always want to see positive findings about new therapies, but some oncologists also noted that the overall healthcare expense associated with a positive finding on this particular study may have created some real dilemmas,” he said.

Genitourinary Cancers
Men with early-stage prostate cancer had about a 29% reduction in the risk of metastasis and 28% improvement in survival when they received adjuvant radiation therapy following radical prostatectomy. ASCO cancer specialists called the trial a “practice-changing study.”

Two different drugs received FDA approval for treatment of renal-cell carcinoma. Everolimus (Afinitor), an inhibitor of mammalian target of rapamycin (mTOR) demonstrated activity in patients whose cancer had not responded to prior targeted therapy.

Bevacizumab was approved for use in combination with interferon to treat metastatic renal cell carcinoma. Two different trials showed almost a doubling of progression-free survival with the bevacizumab combination compared with interferon alone, although overall survival improved only modestly.

Gynecologic Cancers
Quarterly measurement of CA125 following treatment for ovarian cancer did not reduce the risk of recurrence. The findings from a European study showed that patients did not benefit from early treatment for relapse or recurrence based on CA125 results.

Data from a large multicenter clinical trial demonstrated the efficacy of the human papillomavirus vaccine in older women. The vaccine protected women ages 24 to 45 from HPV infection and both benign and malignant disease of the cervix and genitalia in more than 90% of cases. ASCO specialists said the results show that older women who have not been infected by HPV may derive the same benefits observed in girls and younger women.

Lung Cancer
Maintenance therapy with pemetrexed (Alimta) significantly improved survival in patients with stage IIIB or IV nonsquamous, nonsmall-cell lung cancer (NSCLC). The trial was the first to demonstrate a survival benefit with maintenance chemotherapy, which should now be considered the standard of care for patients with advanced NSCLC, ASCO cancer specialists concluded.

EGFR mutations predicted response to treatment with gefitinib (Iressa) in Asian patients who were nonsmokers or light smokers. Patients with the mutations had a significant slowing of progression when treated with the targeted agent.

M.D. Anderson’s Fisch cited the mutation study as an example of advances that will “likely guide the best choice of treatment.”

A vaccine that boosts the immune system’s response to cancer doubled the response rate of melanoma when added to interleukin-2 (IL-2). Response rates were 9.7% with IL-2 alone and 22.1% with IL-2 and the vaccine.

Central Nervous System Cancers

FDA approval of bevacizumab provided the first new drug for glioblastoma in a decade. Two different trials demonstrated improved progression-free survival and overall survival in patients with advanced glioblastoma treated with bevacizumab.

A monoclonal antibody that stimulates the immune system reduced the risk of recurrence and improved survival in patients with high-risk neuroblastoma. Known as ch14.18, the immunotherapy was associated with a two-year overall survival of 86% compared with 75% with standard therapy and relapse-free survival of 66% compared with 46%.

Hematologic Malignancies
A patient-specific therapeutic vaccine improved disease-free survival in patients with previously untreated follicular lymphoma. Patients randomized to the vaccine had a disease-free survival of 44.2 months compared with 30.6 months for patients who received a control vaccine.

A targeted agent that homes in on an enzyme involved in inflammation and immune response demonstrated activity against several types of blood cancers in a Phase I clinical trial. Fostamatinib, which inhibits the enzyme Syk kinase, achieved measurable responses in 5% of patients with chronic lymphocytic leukemia, 21% of patients with diffuse large-cell lymphoma, 11% of patients with mantle-cell lymphoma, and 10% of patients with follicular lymphoma.

Cancer Prevention and Screening
Two large randomized clinical trials showed that routine screening for prostate cancer with PSA tests had little or no effect on prostate cancer mortality. ASCO cancer specialists said the message from the trials is that routine PSA testing detects a large number of clinically insignificant cancers and can lead to unnecessary treatment.

The University of North Carolina’s Muss said the PSA studies and the trial that evaluated CA125 as a guide to therapy both should have a practice-changing impact on oncology.

The ASCO report also reviews the organization’s major recommendations for the past year, emphasizing ASCO’s support for increased funding for cancer research and removal of regulatory barriers to research, implementation of quality-of-care measures for cancer care, and elimination of barriers to access to high-quality cancer care.

Focusing on policy issues, Roy Jones, MD, of M.D. Anderson, cited a need for insurance coverage that addresses the impact of new technology on the cost of healthcare. He suggested a two-tiered system of coverage comprising a basic insurance plan for “proven cost-effective care” and supplemental policies that “willing purchasers would pay for the privilege of unproven high-tech.”

“Since the current healthcare reform proposals fail to address the major cost driver, they are all unlikely to reduce costs,” said Jones. “On that pessimistic note, we might be able to consider this or similar plans the ‘go round.'”

1. This article was developed in collaboration with ABC News.
2. Primary source: Journal of Clinical Oncology
3. Source reference: Petrelli N, Winer EP, eds “Clinical cancer advances 2009. Major research advances in cancer treatment prevention, and sceening” J Clin Oncol Epub.

November, 2009|Oral Cancer News|