Targeted cancer therapy kills prostate tumor cells, study finds

ScienceDaily (June 6, 2011) — A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds.

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The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.

"This targeted therapy may provide a treatment breakthrough that will extend the lives of men with advanced, hormone-refractory prostate cancer," said lead investigator Shuk-mei Ho, PhD, chairwoman of the Department of Environmental Health at the University of Cincinnati.

Men with prostate cancer that has recurred or has spread outside the prostate routinely receive androgen deprivation therapy, which blocks the action of the male hormones. This castration occurs through surgical removal of both testes or more often with medications. Although effective, this hormone-blocking treatment eventually stops working in some patients, Ho said.

"These patients are left with very few treatment options and usually succumb quickly to the disease," she said.

Ho's team previously found they can inhibit the growth of prostate cancer cell lines in culture by targeting and activating a protein called G protein-coupled receptor 30 (GPR30) using the experimental drug G-1, a GPR30 agonist, or stimulator.

In their new study, funded by the Veterans Affairs and the National Institutes of Health, Ho and her co-workers tested G-1 in an animal model of castration-resistant prostate cancer. They implanted human prostate cancer cells beneath the skin of male mice. The established tumor regressed upon castration and after the cancer relapsed, they injected the mice with a low dose of G-1. They also gave G-1 to noncastrated, or "intact," male mice that had prostate tumors. In these intact mice that still had male hormones, G-1 did not stop growth of the prostate tumors or cause substantial death of tumor cells (necrosis), they found.

"Surprisingly, G-1 was highly effective in halting the growth of the tumors that re-emerged after castration," Ho said.

The castration-resistant tumors showed a 65 percent necrosis. These mice had increased expression of GPR30 after castration, which Ho believes sensitized prostate tumors to the cell growth-inhibiting effects of G-1.

"These results mean G-1 won't work without androgen deprivation therapy," she said.

Therefore, Ho reported, the window of time when this targeted therapy might be effective for treating hormone-resistant prostate cancer is after androgen deprivation therapy. She said she believes G-1 can make androgen blockade more effective. G-1 caused no harm to the prostate or other vital organs in mice, she added.

Although GPR30 may have a role in cell growth in female tissues, Ho said it appears to have the opposite effect in men with hormone-resistant prostate cancer. "The beauty of this GPR30 is that it does not have any estrogen, and so it will not cause any side effects of estrogen," she said.

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High-impact radiopeptide therapy halts neuroendocrine cancer

ScienceDaily (June 6, 2011) — Research introduced at SNM's 58th Annual Meeting could be a sign of hope for patients with neuroendocrine cancer not responding well to standard therapies. Most radiotherapies use medical isotopes that emit beta radiation. The therapy in this study employs alpha particles, which have potential for higher potency. In fact, one single atom could be enough to kill an entire cancer cell.

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"Until now, the usage of alpha radionuclides was limited to direct injection into the tumor or the use of only very small doses," says Clemens Kratochwil, MD, lead author of the study from the University of Heidelberg, Heidelberg, Germany, and the Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe, Germany. "This is the first patient study of dose escalation involving the injection of a specific tumor-targeted peptide tagged with an alpha-emitter. This provides additional options for patients with therapy-resistant cancers; further studies could expand the development and safe use of alpha-emitter therapies for patients with other forms of cancer."

Neuroendocrine cancer affects cells that translate neuronal information into hormonal information. Hormones and neuroendocrine nerve cells control a range of physiological processes, including efficiency of digestion, cellular metabolism, blood flow and the reproductive cycle. This type of cancer can therefore affect organs including the pancreas, the bowel, the thyroid gland and the lungs, among many others. Neuroendocrine cancer can go undetected for years and spread (metastasize) to other organs, especially the liver, bones and lymph nodes.

Standard therapy for neuroendocrine cancer is surgery and chemotherapy, as well as radiotherapy. Radiotherapy uses ionizing radiation to kill cancer cells by damaging their DNA. More targeted therapies come in the form of radioimmunotherapy and radiopeptide therapy, comprising a radionuclide bound or used in conjunction with an antibody or peptide that specifically targets the cancer tissue. A range of radionuclides, also known as medical isotopes, are used depending on the type of cancer, the kind of tumor and stage of disease. Most radiotherapies use beta-emitting particles, but more recently researchers have been conducting studies regarding the use of alpha-emitting particles, which have a very near-range and high-energy effect where administered. The benefit of alpha-therapy is its high cytotoxicity, or ability to kill cells -- both cancerous and healthy cells. For this reason, scientists must test the safety of alpha-therapy and identify the most appropriate dose to avoid toxicity in normal tissues.

This study is focused on a cancer therapy called 213Bi-DOTATOC peptide receptor alpha-therapy. DOTATOC, as a tumor-targeting probe labeled with different radionuclides, has been under investigation in the University Hospital of Heidelberg for more than a decade. This peptide analog mimics the endocrine-system regulating hormone somatostatin. The latest advance for the treatment is the use of alpha-emitter 213 Bismuth, a radionuclide that is bound to DOTATOC and injected. Researchers administered the therapy to 14 patients with neuroendocrine liver metastases resistant to previous treatment with beta-particle peptide therapy. The therapy was found to be highly effective for targeting neuroendocrine tumors and inducing remission of metastases without dangerous toxicity to healthy tissues. Further studies are scheduled to escalate dosage further for even greater cancer-killing power for metastatic neuro-endocrine cancer patients. Additional alpha-emitter therapy studies are also continuing to determine their efficacy for treating other therapy-resistant cancers.

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Intensity modulated radiation therapy cuts GI side effects from prostate cancer in half vs. 3D-CRT, study shows

ScienceDaily (June 1, 2011) — Intensity modulated radiation therapy, a newer, more precise form of radiation therapy, causes fewer gastrointestinal side effects when combined with hormone therapy than using three-dimensional radiation therapy, according to a study published in the June issue of the International Journal of Radiation Oncology•Biology•Physics, the official scientific journal of the American Society for Radiation Oncology (ASTRO).

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Three-dimensional radiation therapy (3D-CRT) combined with hormone therapy has been proven very effective at treating men with intermediate to high-risk prostate cancer. However, these treatments can cause very uncomfortable gastrointestinal side effects due to exposure of the rectum to radiation during treatment.

Researchers at Fox Chase Cancer Center in Philadelphia conducted a study to see if IMRT, which allows doctors to better concentrate radiation in the prostate and limit rectal exposure, reduces the side effects while continuing to deliver the necessary radiation to successfully treat the cancer.

Two hundred ninety-three men were studied -- 170 received 3D-CRT and 123 received IMRT. With a mean follow-up of 86 months, a multivariate analysis shows that patients treated with 3D-CRT were more than twice as likely to develop gastrointestinal toxicity compared to patients treated with IMRT.

"The use of IMRT significantly reduces the risk of late GI toxicity in men undergoing concurrent radiation therapy and hormone therapy for prostate cancer," Mark Buyyounounski, MD, MS, a radiation oncologist at Fox Chase Cancer Center, said. "I encourage men with prostate cancer receiving hormone therapy and radiation therapy to talk their doctors about whether IMRT has advantages over other types of radiation therapy."

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Pleural mesothelioma: Combination therapy shows promise for rare, deadly cancer caused by asbestos

ScienceDaily (June 2, 2011) — Pleural mesothelioma patients who undergo lung-sparing surgery in combination with photodynamic therapy (PDT) show superior overall survival than patient treated using the conventional therapy of extrapleural pneumonectomy (EPP) (or en bloc removal of the lung and surrounding tissue) with PDT, indicates new research from the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania. The research is published in the June 2011 issue of the Annals of Thoracic Surgery.

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"Unlike patients who receive traditional lung sacrificing surgery for mesothelioma, the patients in our study who underwent lung sparing surgery and photodynamic therapy, a light-based cancer treatment, have experienced unusually long overall survival rates. The median survival for those patients had not been reached at over two years when the results were analyzed. That's unusual in this field, especially when the majority of those patients are older and have advanced cancer," said Joseph Friedberg, MD, co-director of the Penn Mesothelioma and Pleural Program and the thoracic surgeon who performed the operations cited in the study. "In addition to the overall survival statistics, the difference between having and not having a lung, both with respect to the risk of surgery and the ability to enjoy a normal life after surgery, is crucial for these patients."

Mesothelioma is one of the most aggressive and deadliest forms of cancer and is usually caused by exposure to asbestos. Exposure to asbestos typically precedes development of the cancer by anywhere from 10 -- 50 years, but once it occurs, the average survival rate following diagnosis is often only 9-12 months.

Although mesothelioma can occur in other locations like the abdomen, pleural mesothelioma is the most common form of the disease and accounts for roughly 70 percent of cases. This form originates in the pleura -- the membrane surrounding the lung and lining the chest -- where it starts off as a microscopic sheet of malignant cells that coats the interior of the chest and can grow to be several inches thick. The coating and enveloping nature of the cancer makes it impossible to completely remove it with surgery alone. As a result, the conventional surgery-based approach to treatment involves radical surgery that includes removing the lung, in combination with chemotherapy and whole chest radiation. Even with this aggressive treatment, the disease will recur in almost all patients.

The current study had two goals. The first was to determine if using a new combination of PDT and surgery would allow a less extensive surgical procedure to be used in lieu of an EPP. The second was to determine if, based on previous research from Penn with PDT, the treatment would have any positive effect on survival for patients.

Unlike radiation, which passes through the body, the PDT therapy used in the current study penetrates only a short distance which allows the lung to be preserved. The PDT treatment aims to eradicate the remaining microscopic disease trigger a patient's own immune system to help fight cancer. Penn is one of only two centers in the world where PDT is used to treat pleural mesothelioma.

In the study, 28 patients (19 men, 9 women) underwent surgical resection plus PDT for pleural mesothelioma. Patients were aged from 27 to 81 years. All patients were seen in a multidisciplinary setting and educated about the spectrum of treatment options available, including surgical intervention and its currently investigational status. Of the study group, 14 patients were treated by modified extrapleural pneumonectomy (MEPP) and 14 by radical pleurectomy (RP) and intraoperative PDT. Twenty-two of the 28 patients also received chemotherapy.

Demographics in the MEPP and RP cohorts were similar in age, sex, stage, nodal status, histology, and adjuvant treatments. Stage III/IV disease was present in 12 of 14 patients (86 percent) in both groups. The median overall survival for the patients who received the MEPP treatment was 8.4 months. At a follow-up 2.1 years after the end of treatment, a median survival rate for the patients who received a radical pleurectomy had not yet been reached. The results yielded by the radical pleurectomy and adjuvant PDT were superior to other studies of surgical treatment plans with patients of similar demographics.

"Our primary motivation in attempting the lung sparing surgery was preservation of quality of life, and we were hoping the survival results would at least be similar to the more traditional pneumonectomy approach," said Friedberg. "Although our pneumonectomy results were in line with what is often reported for similar patients having surgery-based treatments, we were completely caught off guard when the analysis revealed a significantly longer survival for the patients who retained both lungs."

Although all patients in the current study received the PDT therapy in combination with a different surgical technique, the researchers further note that the use of intraoperative PDT is the evident difference between the multimodal protocol used in the current study and other standard treatment options presently in use, and it seems worth speculating on any potential direct contributions of the PDT to the overall survival rates.

"Why this is happening is unclear and has emerged as the focus of our continuing research," said Friedberg. The possibility exists that the residual PDT-treated microscopic disease induced an autologous tumor vaccine effect or potentially enhanced the effect of adjuvant treatments.

"This study has limitations, as many mesothelioma studies do, but these results are very encouraging. The findings from our study are particularly notable because many of the patients in this study would often be excluded from surgery-based therapy because of their advanced age or unfavorable oncologic characteristics such as the large bulk of their cancers or the spread to the lymph nodes," said Dr. Friedberg. "Based on these results this lung-sparing technique, combined with photodynamic therapy, has become the backbone of our surgery-based treatment protocols."

A larger study investigating the efficacy of this multimodal approach is currently underway at Penn.

The Penn Mesothelioma and Pleural Program is a unique program that consists of a multidisciplinary team of dedicated specialists with a passion and expertise for treating patients with these difficult cancers. The Penn Program offers a true multidisciplinary approach, presenting patients with essentially all treatment options offered world wide and a number of treatments offered only at Penn.

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Emerging trends in radiation therapy for women over 70 with early stage breast cancer

ScienceDaily (June 2, 2011) — Patterns of radiation usage in breast conserving therapy for women 70 years and older with stage I breast cancer are changing: more women are opting for radioactive implants and those with estrogen positive tumors are opting out of radiation therapy, according to an abstract being presented at the American Society of Clinical Oncology annual meeting in Chicago by Thomas Jefferson University Hospital researchers.

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In another abstract, the researchers report that women with estrogen negative tumors were 91 percent more likely to die from breast cancer if they did not receive radiation therapy after a lumpectomy.

Given the relatively recent developments in radiation therapy (i.e., an increased use of brachytherapy and external beams) and data supporting the idea that radiation isn't necessary for women with estrogen positive tumors, researchers wanted to see how actual practice patterns were impacted.

Researchers found that there was a modest increase in the percentage of women with estrogen receptor positive cancers who did not get radiation therapy starting around 2004, and increasing use of radioactive implants, such the MammoSite, Contura, Savi or similar devices, since 2002.

There was also a corresponding drop in women who received external beam radiation, according to Xinglei Shen, M.D., a resident in the Department of Radiation Oncology at Thomas Jefferson University Hospital. "Among women with estrogen receptor negative cancers, there was not the same increase in frequency of women who did not get radiation, but there was an increased use of radioactive implants," he said.

The consequence of those findings was determining what impact omitting radiation has on survival. While there is data that the omission of radiation therapy in women with estrogen receptor positive tumors who receive endocrine therapy, such as Tamoxifen, is not associated with a survival difference, limited data exists for estrogen receptor negative tumors in older women who undergo breast conservation.

"From the randomized trial data, we know that women with estrogen receptor positive stage I breast cancer have no detriment to survival by avoiding radiation, as long as they took Tamoxifen," Dr. Shen said. "However, it is unknown if this would be the case in women with estrogen receptor negative cancer."

Dr. Shen worked with Jefferson Medical College student Andrzej Wojcieszynski to examine survival in these women, and found that they were 91 percent more likely to die from breast cancer if they did not receive radiation therapy after a lumpectomy. (Abstract #1037).

"We have to be cautious when interpreting survival data from the SEER because of potential confounding variables, such as the health of the patients and use of chemotherapy," Dr. Shen said. "However, these data do raise hypotheses for future study."

"Our conclusion is that adjuvant radiation therapy after lumpectomy reduces breast cancer mortality in women over 70 with stage I, estrogen receptor negative breast cancers, and that radiation is currently underutilized in these women," said Wojcieszynski.

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New therapy for blood cancers using drug combo

ScienceDaily (June 3, 2011) — Reported in the journal Clinical Cancer Research, the study determined the maximum tolerated dose with acceptable side effects for this novel drug combination. The trial represented the first time a proteasome inhibitor such as Bortezomib was combined with a cell cycle inhibitor such as Alvocidib to treat patients with cancer. Proteasome inhibitors work by blocking the action of proteasomes, which are large protein complexes that help destroy proteins that are no longer needed by the cell. Cell cycle inhibitors disrupt the sequence of events that allow cells to undergo cell division and duplication. They also have the ability to block gene transcription.

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The trial included 16 patients who had either indolent (non-aggressive) non-Hodgkin's lymphoma, mantle cell lymphoma or multiple myeloma. After they received the treatments over a 21-day cycle, there were two complete responses, meaning that all detectable traces of the cancer were gone, and five partial responses.

"Therapeutic responses tend to be rare in Phase I trials, but 44 percent of our patient sample responded to the therapy. Interestingly, some patients who previously had no response to Bortezomib, or progressed after Bortezomib therapy, responded to the combination," says Beata Holkova, M.D., a hematologist-oncologist at VCU Massey and co-investigator on this clinical trial. "Because of the small patient sample size, we can't draw definitive conclusions about the effectiveness of the therapy, but we were quite encouraged by the results."

The patients received Bortezomib intravenously on days 1, 4, 8 and 11 and Alvocidib on days 1 and 8. Bortezomib's therapeutic dose alone was not tested because it has already been established and approved to treat certain blood cancers. However, for Alvocidib, the researchers escalated the dose until the maximum tolerated dose was identified. The same researchers are also currently completing a second Phase I clinical trial testing a different delivery schedule of Alvocidib. Although not yet completed, the initial results of this trial appear comparable to the present study.

"This is one of the first trials of its type in which two targeted agents which interfere with two very different biological processes are being combined to treat patients with blood cancers," says co-investigator Steven Grant, M.D., associate director for translational research, co-program leader of Developmental Therapeutics and professor of internal medicine at VCU Massey.

The rationale for this study was developed in Grant's laboratory when synergistic interactions between proteasome and cell cycle inhibitors in malignant blood cancer cells were discovered by Yun Dai, M.D., Ph.D., associate professor of internal medicine at VCU Massey. This laboratory research established the basis for a V Foundation Translational Research Award, which with additional funding from the National Institutes of Health provided the resources necessary to translate the laboratory findings into clinical trials.

Moving forward, the researchers are working with the NCI to develop a Phase II clinical trial to test the effectiveness of this drug therapy. The trial will be conducted in collaboration with multiple institutions to compare the effectiveness of fixed doses of the drug combination in a larger patient population.

Grant and Holkova collaborated with John Roberts, M.D., E. Brent Perkins, M.D., Viswanathan Ramakrishnan, Ph.D., Mary Beth Tombes, R.N., M.N., Ellen Shrader, R.N., Martha Wellons, R.N., Kevin Hogan, Ph.D., Sarah Kolla, M.D., and Talreja, Neha, all from VCU Massey Cancer Center and the VCU School of Medicine; G. David Roodman, M.D., Ph.D., from the University of Pittsburgh Department of Medicine; Domenico Coppola, M.D., Loveleen Kang, Jana Dawson and Daniel Sullivan, M.D., from H. Lee Moffitt Cancer Center and Research Institute; Robert K. Stuart, M.D., from the University of South Carolina Department of Medicine; and William D. Figg, Sr., Pharm.D., Austin Doyle, M.D., and John Wright, M.D., Ph.D., from the National Cancer Institute.

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Benefit of targeted lung cancer therapy confirmed

ScienceDaily (June 3, 2011) — A drug that targets a specific type of lung cancer shows a dramatic response in more than half of the people who take it. The drug, called crizotinib, has been in clinical trials since 2006, and the results from the largest group of patients to take it within the first of these clinical trials are being presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

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The patients taking crizotinib have anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC) and the drug targets the gene that drives this particular kind of cancer. In 119 patients, crizotinib produces some degree of shrinkage in the tumors of the majority of patients with dramatic responses in more than 60 percent of cases. The responses last approximately 48 weeks.

D. Ross Camidge, MD, PhD, the director of the lung cancer clinical program at University of Colorado Hospital (UCH) and the University of Colorado Cancer Center, will be presenting the latest results from the crizotinib trial at ASCO. "The strength of crizotinib in ALK positive lung cancer was apparent when less than 20 patients were taking part in the trial. The benefit of targeting this kind of cancer with this particular drug has only been confirmed as more patients enrolled in the trial," said Camidge. "This demonstrates the efficacy of new drugs can be reliably revealed even among small groups of patients when the cancers being tested are molecularly uniform."

Medical oncologists at UCH care for one of the largest groups of ALK positive lung cancer patients in the world. Approximately one in 20 lung cancer patients is ALK positive -- their responses to crizotinib are dramatic, the side effects are usually mild and often improve over time.

Camidge believes the results being seen with crizotinib open the door to a new way of thinking when it comes to cancer treatment. "We need to continue testing drugs in molecularly defined populations to find out early whether they can be effective. When we try and give targeted drugs to everyone, knowing that cancers are so different between individuals, we run the risk of missing real breakthroughs that only apply to subgroups. You don't have to know definitively what the magic marker for who responds to a particular drug is when you start -- but you can test a series of hypotheses by prescreening patients and really focus on the development of drugs on the right group as early as possible."

Lung cancer is the leading cause of cancer deaths in the United States. Camidge said it is crucial for anyone diagnosed to get their lung tumor tested for ALK and an increasing list of other molecular markers. The University of Colorado helped to develop several of these tests that now reveal that lung cancer is actually several different diseases at the molecular level. Each one may need a different type of treatment.

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Combination antibody therapy shows promise in metastatic melanoma

ScienceDaily (June 3, 2011) — A duo of drugs, each targeting a prime survival strategy of tumors, can be safely administered and are potentially more effective than either drug alone for advanced, inoperable melanomas, according to a phase 1 clinical trial led by Dana-Farber Cancer Institute investigators.

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The findings are being presented in an oral session at the annual meeting of the American Society of Clinical Oncology in Chicago.

The drugs -- ipilimumab and bevacizumab -- are both monoclonal antibodies, intensified formulations of natural disease-fighting proteins. Ipilimumab spurs the immune system to attack diseased cells, including tumor cells. Bevacizumab, also known by the trade name Avastin, blocks the growth of blood vessels that provide tumors with nourishment. Ipilimumab has extended the lives of metastatic melanoma patients in previous clinical trials, and bevacizumab is often used to treat tumors of the colon, lung, and kidney.

The trial involved 22 patients with metatastic melanoma that was not treatable by surgery.

F. Stephen Hodi, MD, the study's lead author and director of the melanoma treatment center at Dana-Farber, said the trial is the first to explore whether the two agents enhance each other's effectiveness. Most of the participants didn't experience serious adverse side effects, although some did experience inflammation of artery walls, the liver, thyroid gland, colon, or uvea (the middle layer of the eye). Five patients required steroid treatment for these problems and were removed the trial.

Positron emission tomography (PET) scans showed a prompt immune system response to many of the melanoma tumors, and computed tomography (CT) scans showed decreased blood flow to the tumors. Eight of the participants had partial responses -- showing some tumor shrinkage -- to the dual treatment, and six had stable disease. All the responses lasted at least six months. Biopsies performed after the treatment showed a more vigorous immune system response than would be expected with ipilimumab alone.

"Our findings indicate that ipilimumab and bevacizumab can be safely administered with careful management of side effects," said Hodi. "The results of lab tests suggest that the two agents may work synergistically, with 14 of 21 evaluable patients experiencing a clinical benefit. This approach merits exploration in further clinical trials."

Funding for the trial was provided by grants from the Melanoma Research Alliance and National Institutes of Health.

The other co-authors of the study are Philip Friedlander, MD, Annick Van Den Abbeele, MD, Nageatte Ibrahim, MD, Xinqi Wu, PhD, Jun Zhou, PhD, Anita Giobbie-Hurder, Travis Hollmann, MD, PhD, Sara Russell, MD, Pamela Dipiro, MD, Jeffrey Yap, PhD, Dana-Farber; George Murphy, MD, David McDermott, MD, Brigham and Women's Hospital; Michael Atkins, MD, Beth Israel Deaconess Medical Center; and Donald Lawrence, MD, Massachusetts General Hospital.

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New made-in-Canada therapy for bladder cancer shows promising results

ScienceDaily (May 24, 2011) — Clinical trials for a new bladder cancer therapy show promising interim results. Lead researcher Alvaro Morales says that the breakthrough using the drug Urocidin follows thirty years of his research in this important area.

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"I am optimistic about the results of the trial," says Dr. Morales, professor emeritus in the Department of Urology at Queen's University and director of the Queen's University Centre for Applied Urological Research. "Positive results in the next phase of trials will move us very close to a far more effective bladder cancer treatment."

Initial human trials found that Urocidin is effective and much safer than previous treatment options for cases of superficial bladder cancer that is not responsive to Bacillus Calmette-Guérin (BCG) therapy. A recent large North American clinical trial confirmed the initial findings, with 25 per cent of patients becoming disease-free after one year of therapy with the new drug. Patients also tolerated Urocidin well.

Dr. Morales spearheaded BCG as a bladder cancer treatment in the 1970s in collaboration with the Cancer Research Institute of New York. BCG provoked an immune response strong enough to eliminate some bladder cancers without chemicals. It was also the first effective agent approved by the FDA against solid tumors. BCG remains the first choice to treat superficial bladder cancer due to its superior efficacy over chemotherapy drugs; however, as a live bacterium, it has the potential for serious adverse effects.

"There has been a lot of concern about the adverse effects of BCG," explains Dr. Morales. "I've always thought that we should look for something better. Urocidin could be what we're looking for." Until the discovery of BCG as a bladder cancer therapy, the only alternative short of bladder removal was to put chemicals into the bladder.

Urocidin was developed by Bioniche Life Sciences Inc. A second Phase III clinical trial is underway, funded by Bioniche's licensing partner, Endo Pharmaceuticals.

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Low-dose sorafenib may improve therapy for head and neck cancer

ScienceDaily (May 16, 2011) — Adding low doses of the targeted agent sorafenib to the chemotherapy and radiation now often used to treat head and neck cancer might significantly improve patient care and quality of life, according to a new study by researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James).

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The findings suggest that adding sorafenib would maintain treatment efficacy while permitting the use of lower doses of chemotherapy and radiation and decreasing the treatment's harsh side effects. The triple combination was well-tolerated in an animal model.

About 49,200 new cases of head and neck cancer are expected in the U.S. this year, and 11,500 people are expected to die of the disease. Treatment is often unsuccessful because the tumors become resistant to both chemotherapy and radiation therapy.

"This pre-clinical study suggests that using low-dose sorafenib along with chemotherapy and radiation could have significantly milder side effects while maintaining effectiveness," says researcher and principal investigator Dr. Pawan Kumar, assistant professor of otolaryngology and a neck surgeon at the OSUCCC -- James.

"Our findings provide a scientific rationale to evaluate this combination strategy through a clinical trial," Kumar added.

The results of the laboratory and animal study are published online in the journal Molecular Cancer Therapeutics, and they include the following:

Sorafenib sensitized tumor cells to chemotherapy and radiation treatment by down-regulating DNA repair proteins (ERCC-1 and XRCC-1), and it decreased tumor angiogenesis by inhibiting VEGF-mediated signaling. The combination treatment was well tolerated in a mouse model and significantly inhibited tumor growth and tumor angiogenesis; low-dose sorafenib alone was an effective maintenance regimen. The combination treatment significantly inhibited tumor-cell migration, invasion and the formation of new tumor blood vessels in laboratory studies.

"Taken together, our results suggest a potentially novel strategy in which sorafenib combined with low doses of chemotherapy, radiation therapy, or both is as effective in the treatment of head and neck cancer as much higher doses used in existing treatment approaches," says study co-author Dr. Theodoros N. Teknos, professor of otolaryngology, director of head and neck oncologic surgery, and the David E. and Carole H. Schuller Chair in Head and Neck Oncologic Surgery. "As a result, it may be possible to design new treatment regimens that limit side effects of therapy without decreasing cure rates."

Funding from the National Cancer Institute and Joan's Fund supported this research.

Other Ohio State researchers involved in this study were Arti Yadav and Bhavna Kumar.

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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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