Coffee drinking improves hepatitis C treatment response, study suggests

ScienceDaily (June 8, 2011) — Advanced hepatitis C patients with chronic liver disease may benefit from drinking coffee during treatment, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute. Patients who received peginterferon plus ribavirin treatment and who drank three or more cups of coffee per day were two times more likely to respond to treatment than non-drinkers.

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"Coffee intake has been associated with a lower level of liver enzymes, reduced progression of chronic liver disease and reduced incidence of liver cancer," said Neal Freedman, PhD, MPH, of the National Cancer Institute and lead author of this study. "Although we observed an independent association between coffee intake and virologic response to treatment, this association needs replication in other studies."

Among non-drinkers, 46 percent had an early virologic response; 26 percent had no detectable serum hepatitis C virus (HCV) ribonucleic acid at week 20; 22 percent had no detectable serum at week 48; and 11 percent had a sustained virologic response. In contrast, the corresponding proportions for those who drank three or more cups of coffee per day were 73 percent, 52 percent, 49 percent and 26 percent, respectively.

Approximately 70 to 80 percent of individuals exposed to HCV become chronically infected. Worldwide, these individuals are estimated to number between 130 and 170 million. Higher coffee consumption has been associated with slower progression of pre-existing liver disease and lower risk of liver cancer. However, the relationship with response to anti-HCV treatment had not been previously evaluated. Treatment with peginterferon and ribavirin resolves chronic hepatitis C in about half of patients. It is unknown whether coffee will improve response with the addition of new drugs that were recently approved for use in the U.S.

Because patients in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial also had previously failed interferon therapy, it is not clear whether the results can be generalized to other patient populations. Future studies among patients with less advanced disease, those who are treatment-naïve to prior therapy, or who are being treated with newer antiviral agents are needed.

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Therapeutic melanoma vaccine improves response rate, progression-free survival, study finds

ScienceDaily (June 2, 2011) — A vaccine for one of the most lethal cancers, advanced melanoma, has improved response rate and progression-free survival for patients when combined with the immunotherapy drug Interleukin-2, according to research led by scientists from The University of Texas MD Anderson Cancer Center and Indiana University Health Goshen Center for Cancer Care.

See Also:Health & MedicineSkin CancerCancerDiseases and ConditionsVaccinesBreast CancerColon CancerReferenceMetastasisClinical trialHPV vaccineTumor suppressor gene

The findings, published in the June 2 New England Journal of Medicine, mark the first vaccine study in the disease -- and one of the first in cancer overall -- to show clinical benefit in a randomized Phase III clinical trial. It's also the first cancer vaccine to show an improved response rate in patients.

The research was first presented on the plenary session of 2009 American Society of Clinical Oncology.

According to the American Cancer Society, melanoma has one of the fastest growing incidence rates of all cancers. In 2010, more than 68,130 people in the U.S. were diagnosed with melanoma and 8,700 died from the disease. The five-year survival rates for those with regional and metastatic disease are 65 percent and 16 percent, respectively.

"Obviously, this is a disease, in its advanced setting, in need of better therapies for patients," said Patrick Hwu, M.D., professor and Chair of the Department of Melanoma Medical Oncology and the study's senior author. "This study serves as a proof-of-principle for the role of vaccines in melanoma and in cancer therapy overall. If we can use the body's own defense system to attack tumor cells, we provide a mechanism for ridding the body of cancer without destroying healthy tissue."

During their tenure at the National Cancer Institute NCI), Hwu and Douglas Schwartzentruber, M.D., the medical director of the Goshen Center for Cancer Care, were involved in the vaccine's development and early basic and clinical studies. The peptide vaccine, known as gp100:209-217 (200M), works by stimulating patients' T cells, known for controlling immune responses.

"This vaccine activates the body's cytotoxic T cells to recognize antigens on the surface of the tumor. The T cells then secrete enzymes that poke holes in the tumor cell's membrane, causing it to disintegrate," explained Schwartzentruber, the study's principal investigator and corresponding author.

After an NCI-led Phase II study combining the vaccine with Interleukin-2 (IL-2) showed response rates of 42 percent in metastatic melanoma patients, a Phase III randomized trial with the two agents opened more than a decade ago.

Conducting a large, multi-institutional trial with IL-2, however, had its own set of unique challenges, explained Hwu, as not all cancer centers and community hospitals are capable of administering the immunotherapy. A highly specialized therapy associated with such significant side effects as low blood pressure and capillary leak syndrome, which poses risks to the heart and lung, IL-2 is often delivered in intensive care units. MD Anderson is one of the few centers with a dedicated in-patient unit exclusively designed for the drug's delivery; before, the institution was offering the therapy in its ICU.

In the Phase III trial, 185 patients at 21 centers across the country were enrolled in the study. All had advanced metastatic melanoma and were stratified for cutaneous metastasis, a known indicator of response to IL-2. Patients were randomized to receive either high dose IL-2, or IL-2 and vaccine. In the IL-2 arm, 94 patients were enrolled and 93 were treated and evaluated for response; 91 were enrolled and 86 treated and 85 were evaluated for response in the IL-2 and vaccine arm. The primary endpoint of the study was clinical response; the secondary endpoints were toxic effects and progression-free survival.

The study found that those who received the vaccine had a response rate of 16 percent, and progression-free survival of 2.2 months, compared to 6 percent and 1.6 months respectively in those that did not. The study was not powered to look at overall survival, but for those receiving the vaccine, it trended positive, 17.8 months vs. 11.1 months.

"This is one of the first positive randomized vaccine trials in cancer and the findings represent a significant step forward for treatment of advanced melanoma," said Schwartzentruber. "However, the vaccine only can be given to half of those with melanoma because it has to match a patient's tissue type, or HLA. A major priority for us is to figure out ways to broaden our approach and use mixtures of peptides, for example, so that more patients are eligible."

The researchers would like to improve upon it by including other immune-stimulatory agents, such as newer vaccine adjuvants, other cytokines and antibodies that further activate immune cells.

"This is a very exciting time for the field of melanoma. During the last few years, the entire landscape has changed -- with the addition of targeted therapies such as those that target BRAF as well as those that stimulate the immune system. Still, these drugs work in a small number of patients, and/or resistance often develops," said Hwu. "Now, our focus will need to turn toward studying these novel therapies in combination and continue our quest for better vaccines, as well as researching ways to make the study inclusive of more metastatic melanoma patients."

The study was funded, in part, by the National Cancer Institute.

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Yoga improves quality of life in women with breast cancer undergoing radiation therapy, study finds

ScienceDaily (May 18, 2011) — For women with breast cancer undergoing radiation therapy, yoga offers unique benefits beyond fighting fatigue, according to new research from The University of Texas MD Anderson Cancer Center.

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While simple stretching exercises improved fatigue, patients who participated in yoga that incorporated yogic breathing, postures, meditation and relaxation techniques into their treatment plan experienced improved physical functioning, better general health and lower cortisol (stress hormone) levels. They also were better able to find meaning in their cancer experience.

The findings, to be presented next month in an oral session at the 47th annual meeting of the American Society of Clinical Oncology by Lorenzo Cohen, Ph.D., professor and director of the Integrative Medicine Program at MD Anderson, are the latest in an ongoing effort to scientifically validate the age-old belief that mind-body interventions have a beneficial impact on the health of cancer patients. The research was conducted in collaboration with India's largest yoga research institution, Swami Vivekananda Yoga Anusandhana Samsthana in Bangalore, India.

The study assessed, for the first time, yoga benefits to cancer patients by comparing their experience with patients in an active control group who integrated simple, generic stretching exercises into their lives. "The combination of mind and body practices that are part of yoga clearly have tremendous potential to help patients manage the psychosocial and physical distress associated with treatment and life after cancer, beyond the benefits of simple stretching," said Cohen.

To conduct the study, 163 women with breast cancer (stage 0-3) averaging 52 years of age were randomized to one of three groups: 1) yoga; 2) simple stretching; or 3) no instruction in yoga or stretching. Participants in the yoga and stretching groups attended sessions specifically tailored to breast cancer patients for one hour three days a week throughout their six weeks of radiation treatment.

Participants were asked to report on their quality of life, including fatigue, daily functioning, benefit finding, depression and spirituality. Saliva samples were collected and electrocardiogram tests were administered at baseline, end of treatment, and at one, three and six months post-treatment.

After completing radiation treatment, only the women in the yoga and stretching groups reported a reduction in fatigue. At one, three and six months after radiation therapy, women who practiced yoga during the treatment period reported greater benefits to physical functioning and general health. They were more likely to perceive positive life changes from their cancer experience than either other group.

Women who practiced yoga also had the steepest decline in their cortisol across the day, indicating that yoga had the ability to regulate this stress hormone. This is particularly important because higher stress hormone levels throughout the day, known as a blunted circadian cortisol rhythm, have been linked to worse outcomes in breast cancer.

According to Cohen, developing a yoga practice also helps patients after completing cancer treatment. "The transition from active therapy back to everyday life can be very stressful as patients no longer receive the same level of medical care and attention. Teaching patients a mind-body technique like yoga as a coping skill can make the transition less difficult."

Through a grant from the National Cancer Institute -- the largest ever awarded for the study of yoga in cancer -- Cohen and his team will next conduct a Phase III clinical trial in women with breast cancer to further determine the mechanisms of yoga that lead to improvement in physical functioning, quality of life, and biological outcomes during and after radiation treatment. A secondary aim of the trial, but one of great importance, stressed Cohen, is assessing cost efficiency analysis for the hospital, health care usage costs in general, and examining work productivity of patients.

MD Anderson recognizes the growing body of research indicating that relaxation-based interventions can contribute to the well-being of people with cancer. Through the Integrative Medicine Program, complementary therapies, such as yoga, are offered at MD Anderson's Integrative Medicine Center, and are used in concert with mainstream care to manage symptoms, relieve stress, enhance quality of life, and improve outcomes for patients and their caregivers. MD Anderson's Integrative Medicine faculty also conduct research in the biological and behavioral effects of mind-body based interventions; the anti-cancer potential of natural compounds; and, acupuncture to treat common cancer treatment-related side effects.

In addition to Cohen, other MD Anderson researchers contributing to this study include: Kavita Chandwani, M.D., former senior research coordinator and yoga teacher; Robin Haddad, M.P.H. , research coordinator, George Perkins, M.D. in the Department of Radiation Oncology; Amy Spelman, Ph.D., Kayla Johnson, B.S. and Adoneca Fortier, B.S., all staff in the Integrative Medicine Program; Banu Arun, M.D., in the Department of Breast Medical Oncology; and Qi Wei, M.S., Sr. Statistical Analyst. Clemens Kirschbaum, Ph.D. contributed from the Technical University of Dresden, Dresden, Germany. Collaborators from SVYASA include NV Raghuram, B.E.; R. Nagarathna, M.D., and HR Nagendra, Ph.D., founder.

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Curcumin compound improves effectiveness of head and neck cancer treatment, study finds

ScienceDaily (May 19, 2011) — A primary reason that head and neck cancer treatments fail is the tumor cells become resistant to chemotherapy drugs. Now, researchers at the University of Michigan Comprehensive Cancer Center have found that a compound derived from the Indian spice curcumin can help cells overcome that resistance.

See Also:Health & MedicineBrain TumorOvarian CancerLung CancerPlants & AnimalsBiologyMiceBiotechnologyReferenceMetastasisTumor suppressor geneNanomedicineLung cancer

When researchers added a curcumin-based compound, called FLLL32, to head and neck cancer cell lines, they were able to cut the dose of the chemotherapy drug cisplatin by four while still killing tumor cells equally as well as the higher dose of cisplatin without FLLL32.

The study appears this week in the Archives of Otolaryngology -- Head and Neck Surgery.

"This work opens the possibility of using lower, less toxic doses of cisplatin to achieve an equivalent or enhanced tumor kill. Typically, when cells become resistant to cisplatin, we have to give increasingly higher doses. But this drug is so toxic that patients who survive treatment often experience long-term side effects from the treatment," says senior study author Thomas Carey, Ph.D., professor of otolaryngology and pharmacology at the U-M Medical School and co-director of the Head and Neck Oncology Program at the U-M Comprehensive Cancer Center.

That tumors become resistant to cisplatin is a major reason why head and neck cancer patients frequently see their cancer return or spread. It also plays a big role in why five-year survival for head and neck cancer has not improved in the past three decades.

FLLL32 is designed to sensitize cancer cells at a molecular level to the antitumor effects of cisplatin. It targets a key type of protein called STAT3 that is seen at high levels in about 82 percent of head and neck cancers. High levels of STAT3 are linked to problems with normal cell death processes, which allow cancer cells to survive chemotherapy treatment. STAT3 activation has been associated with cisplatin resistance in head and neck cancer.

Curcumin is known to inhibit STAT3 function, but it is not well-absorbed by the body. FLLL32 was developed by researchers at Ohio State University to be more amenable to use in people. The current study used the compound only in cell lines in the laboratory.

In the current study, researchers compared varying doses of cisplatin alone with varying doses of cisplatin plus FLLL32 against two sets of head and neck cancer cells: one line that was sensitive to cisplatin and one line that was resistant.

They found that FLLL32 decreased the activation levels of STAT3, sensitizing both resistant and sensitive tumor cells to cisplatin. Further, lower doses of cisplatin with FLLL32 were equally effective at killing cancer cells as the higher doses of cisplatin alone.

Separate studies suggest FLLL32 may not be well-absorbed by the body and researchers are developing a next generation compound that they hope improves on that. The U-M team plans to further study this newer compound for its potential as part of head and neck cancer treatment. Clinical trials using this compound are not currently available.

Additional authors include Waleed M. Abuzeid, M.B.B.S.; Samantha Davis, B.S., M.D.; Alice L. Tang, B.A., M.D.; Lindsay Saunders, B.S.; J. Chadwick Brenner, M.S.E.; Emily Light, M.S.; Carol R. Bradford, M.D.; and Mark E.P. Prince, M.D., all from U-M; Jiayuh Lin, Ph.D., from the Nationwide Children's Hospital, Columbus, Ohio; James R. Fuchs, Ph.D., from The Ohio State University.

Funding was provided by the National Institute of Dental and Craniofacial Research, Head and Neck Specialized Program of Research Excellence (SPORE) grant, National Cancer Institute, American Cancer Society

Head and neck cancer statistics: 36,540 Americans will be diagnosed with head and neck cancer this year and 7,880 will die from the disease, according to the American Cancer Society.

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