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Odds & Ends Abstracts by Tom Swartz and Bruce Shriver
In this issue: Venous Clots Common in Young Sarcoma Patients Researchers have found that venous blood clots, although frequently asymptomatic, are nonetheless common in children and young adults with sarcoma. In 122 consecutive sarcoma patients diagnosed and treated at the National Cancer Institute, 19 (16%) had a total of 23 thromboembolic events, according to Ido Paz-Priel, M.D., of Johns Hopkins, and colleagues. Of the 23 events, 46% were detected only incidentally. The findings are reported in the April 20 issue of the Journal of Clinical Oncology. The findings suggest that children and young adults with sarcomas "should be monitored carefully for the development of thromboembolic events and suggestive symptoms should be pursued aggressively," the researchers said. Sarcoma, like most cancer, is conducive to thrombosis because tumor cells promote coagulation and secrete cytokines that trigger inflammation, the researchers noted. Other factors, such as chemotherapy, surgery, immobilization, and having a central venous access device, can also increase the risk of blood clots.
The researchers analyzed records of consecutive patients diagnosed and treated from October 1980 through July 2002 only at NCI's Pediatric Oncology Branch. Of the 122 patients for whom data were available, 61 had Ewing's sarcoma, 20 had osteosarcoma, 26 had rhabdomyosarcoma, and the rest had other sarcomas. The rate of thromboembolism was similar for each type -- 10% for osteosarcoma, 13% for Ewing's sarcoma, 15% for rhabdomyosarcoma, and 33% for the other forms combined. The study also found:
The researchers said the study suggests that patients with metastatic disease are more likely to have thromboembolic events, although the difference did not reach statistical significance. Emboli developed in 23% of patients with metastatic disease at presentation, compared to 10% of those with localized disease. Because the awareness of thrombosis has increased over time, the researchers compared the prevalence of events before and after 1993. More patients presented with metastatic disease before the cutoff than after -- 44% versus 34%, a difference that was significant. However, the researchers found, only 7% of the early patients were diagnosed with a thromboembolic event, compared with 23% in the most recent period. The differences are "likely to due to improved imaging and increased index of suspicion," the researchers said. One implication of that fact, they added, is that the current data "likely underestimate the true magnitude of this problem." Such clotting events are important because "thromboembolism is a potentially life-threatening complication that is almost always amenable to therapy," according to co-author Alan Wayne, M.D., clinical director of the Pediatric Oncology Branch.
The Desmoid Tumor Research Foundation has raised approximately $700,000 to fund research The Desmoid Tumor Research Foundation has raised approximately $700,000 since December 2005 to fund research The Desmoid Tumor Research Foundation has raised approximately $700,000 since December 2005 to fund research to find a cure for this rare disease. Currently DTRF is funding (3) multi-year studies at MD Anderson, Huntsman Cancer Center and The Hospital for Sick Children in Toronto. DTRF held their Second Annual Fundraiser on May 31st at Seasons Catering in Washington Township, NJ. It was a huge success raising over $175,000 for research! The event was attended by over 270 people who enjoyed music, good food, and a silent/live auction. Dr. Dina Lev from MD Anderson Cancer Center, one of the 2006 grant recipients, spoke about the challenges of having a rare disease. A video presentation from desmoid patients around the country also made an impact highlighting the difficulty with living with desmoid tumors. A patient support meeting was held immediately before the event where a video of Dr. Alman's (Hospital for Sick Kids in Toronto) research was shown and a presentation was made by Dr. Dina Lev, giving details of her recently published paper on desmoid tumors. The patients and their families had an opportunity to meet and tell their individual stories. For many, this was their first experience to meet other people suffering from this disease.
The Cancer Screening, Treatment and Survivorship Act of 2007 The Cancer Screening, Treatment, and Survivorship Act of 2007 is legislation currently pending before Congress which would amend the Public Health Service Act and the Social Security Act to improve the screening and treatment of cancers and to provide for survivorship services. The full text of the act is available on the Library of Congress’ Thomas System. The Lance Armstrong Foundation is spearheading an effort to ensure passage of this Act. Please Visit Here to learn how you can help enact this important legislation.
Canadian Cancer Society Invests Nearly $5-million in British Columbia Researchers The Canadian Cancer Society has awarded more than $4.8-million to nine cancer research projects in British Columbia. The Society's total research investment across Canada in 2007-08 is over $47-million and includes 78 new grants. More than 500 research teams coast-to-coast are currently receiving funds from the Canadian Cancer Society. "Advances in research over the past few decades have transformed our understanding of cancer," said Cathy Adair, vice president of strategic initiatives for the Canadian Cancer Society, B.C. and Yukon Division. "Research has made tremendous improvements in the quality and quantity of life for cancer patients through better treatments, new drug discoveries, earlier detection methods, and additional insights on how to prevent and manage cancer. Research is a cornerstone of the Society's efforts to control cancer. Since 1948, the Canadian Cancer Society has funded nearly $1-billion in cancer research and achieved numerous breakthroughs, says Adair.
One of the nine new Canadian Cancer Society-funded grants to British Columbia researchers went to Dr. Torsten Nielsen, of the University of British Columbia who will receive $702,345 over five years. Dr. Nielsen's team is applying new diagnostic tools and drugs developed using both cell cultures and lab mice to deal with synovial sarcoma (cancer of the muscle, fat, fibrous tissues and blood vessels). Based on his team's previous research, these tests and drugs will now be assessed in human cases of synovial sarcoma to prove their clinical value and possibly lead to treatment of other closely-related cancers.
Deadly Cancers Dealt A Knockout Punch By Oncolytic Viruses New scientific evidence is helping to build a compelling case for oncolytic viruses as a first-line and adjunctive treatment for many cancers. Reovirus, a non-pathogenic virus under development at Oncolytics Biotech, has shown powerful anti-cancer activity against cultured tumor cells, in animal models, and in human clinical trials. Oncolytics' proprietary reovirus formulation, Reolysin®, is active against numerous cancers, including intractable sarcomas and melanomas. Recent studies also indicate that Reolysin works synergistically with standard anti-cancer drugs, providing significantly stronger responses than either agent alone. In addition, other studies completed in the past year have shown Reolysin has the ability to prime patients' immune systems against their particular cancer, leading to additional cancer cell killing. It is through this second "inflammatory" mechanism that researchers hope Reolysin will bring about long-term remissions of once-untreatable cancers.
At the Fourth International Conference on Oncolytic Viruses as Cancer Therapeutics in Scottsdale, Arizona, several presentations focused on reovirus efficacy alone or in combination with standard chemotherapies. In one study, investigators examined the tumor-killing ability of reovirus plus cisplatin, a standard chemotherapy agent, in a mouse melanoma model that included both cultured cells and live animals. The results of the preclinical study showed that the combination of reovirus and cisplatin was significantly more effective than cisplatin or reovirus alone at killing melanoma cancer cells in a mouse model. The investigators intend to explore the mechanism of this promising synergistic action in further detail in future preclinical work.
Another presentation at the Arizona conference reported on the use of Reolysin plus the cancer drug cyclophosphamide in an animal model of melanoma. When treated with both agents, test animals experienced enhanced tumor regression compared with either agent alone, and without additional toxicity. Oncolytics has permission from the U.K. regulatory authorities to test Reolysin in three separate human trials in combination with the cancer drugs gemcitabine, paclitaxel/carboplatin and docetaxel.
Perhaps the most exciting findings of Reolysin combination therapy were reported at the American Association for Cancer Research Annual Meeting. In mice transplanted with a human colon cancer, Reolysin plus gemcitabine completely eradicated the tumors in four of five test animals. "Combination therapy results for reovirus in animals are particularly encouraging because they suggest that Reolysin can improve the anti-tumor activity of standard chemotherapy agents in advanced cancer patients without causing additional toxicity," said Dr. Karl Mettinger, Chief Medical Officer of Oncolytics. Physicians often prefer to treat cancer with multiple agents, but toxicity limits these approaches. Since reovirus typically is not pathogenic in humans nor associated with severe toxicity in clinical studies, its co-administration is not expected to increase a treatment's overall toxicity.
Reovirus works by entering and replicating within cancer cells containing an activated ras pathway, a mutation present in about two-thirds of all human cancers. Reovirus enters a cancer cell, makes thousands of copies of itself, and then causes the cell to burst, which releases viruses that infect and kill adjacent cancer cells. Normal cells are not harmed. In addition to killing cancer cells directly, reovirus is believed to activate an anti-tumor immune response through the body's natural killer cells and T cells. Through this mechanism, which persists for weeks or months, the body continues to fight off cancer long after the virus clears from the body.
On April 11, 2007, Oncolytics announced it had initiated a Phase II trial to evaluate intravenous administration of Reolysin in patients with sarcomas that have metastasized to the lung. For patients with deadly soft tissue sarcoma, the lungs are the most common site of metastatic disease. To date, surgery has been the only effective therapy for metastatic sarcoma. The multi-center, Phase II study follows successful completion of systemic administration trials with Reolysin in the U.K. and the U.S. This will be the second of several Phase II trials Oncolytics plans for 2007. The Company also has a collaborative agreement with the U.S. National Cancer Institute to conduct multiple clinical trials with Reolysin which are expected to begin in 2007, including a Phase II melanoma trial and a Phase I/II ovarian cancer trial.
Hand in Hand: The Suzanne R. Leider Memorial Assistance Fund The following excerpt is taken from the Sarcoma Alliance's website: "Hand in Hand offers specific financial assistance for second opinion consultations by reimbursing expenses related to travel, phone bills, costs of the evaluation and directly related charges. Grants up to $1000 annually (per patient) are offered on a quarterly basis to qualified applicants. These grants, though modest, will allow us to touch as many patients’ lives as possible. We inaugurated Hand in Hand as part of our celebration of Sarcoma Awareness Week, June 9th – June 15th, 2003. Hand in Hand pilot program applications are available for downloading from our website."
Drug May Help Combat 'Chemo Brain' A so-called "genius pill" may help breast cancer survivors suffering from the syndrome known as "chemo brain," new research suggests. The small study involved the drug modafinil (Provigil), which was originally approved to treat excessive sleepiness associated with narcolepsy. "This drug actually improved complaints of memory and attention deficit with chemo brain," said study author Sadhna Kohli, a research assistant professor at the University of Rochester's James P. Wilmot Cancer Center. "The results are preliminary and need to be replicated in a larger patient population." The results were presented at the annual meeting of the American Society of Clinical Oncology in Chicago. "This is a small study. It's really the first of its kind, but I think what's important about it is that they did show improvement in some parameters," added Dr. Christine Pellegrino, director of the Breast Clinic at the Montefiore-Einstein Cancer Center in New York City. "This really is opening a door to a potential promise for a lot of patients, not just breast cancer patients, who feel the haziness of chemo brain."
Modafinil belongs to a class of drugs called eugeroics, which stimulate the brain only as required. The effects last about 12 hours. Many people undergoing chemotherapy for cancer complain of memory and attention problems as well as sluggishness, apparently related to the chemotherapy. "We usually associate nausea, vomiting and hair loss as more common side effects [of chemotherapy], but this side effect is a great topic of conversation," Kohli said. "They can't describe it exactly, but they can't function as they did before." In a separate study, Kohli found that 82 percent of almost 600 cancer patients reported memory and concentration problems, which can lead to job loss or social problems.
There are no real options to treat chemo brain. Some patients have tried the stimulant Ritalin, but it can be addictive and has other side effects. "At this point, there's really nothing directed at chemo brain," Pellegrino said. "There's been some look at Ritalin, which is an amphetamine, to try to perk people up, but there hasn't really been anything successful. The nice thing about modafinil is that, unlike Ritalin, it's non-addictive." The new study, funded by Cephalon Inc., the maker of modafinil, and the National Cancer Institute, involved 68 women who had completed treatment for breast cancer. The women ranged in age from 33 to 83, with a median age of 54 years. All participants took 200 milligrams of modafinil for the first four weeks of the trial. During the second four weeks, women who had had a positive response to the drug were randomly selected to continue taking modafinil or a placebo. The women who took modafinil for the entire eight weeks reported significant improvements in certain measures of memory, concentration and learning.
Epeius Biotechnologies Corporation announced on June 4th the expansion of ongoing clinical trials using Rexin-G(TM) in the United States to include breast cancer and all types of sarcomas that have failed standard chemotherapy. Following on the heels of their landmark clinical trials in the United States and abroad, the US FDA granted Orphan Drug Status for Rexin-G for the treatment of pancreatic cancer, while the Philippine BFAD granted Expanded Access Use of Rexin-G for the treatment of all chemo-resistant solid tumors. Rexin-G is the world's first tumor-targeted nanomedicine -- a targeted gene delivery system that seeks out and destroys both primary tumors and metastatic cancers that have spread throughout the body. Delivered by simple intravenous infusion, Rexin-G has demonstrated unprecedented single-agent efficacy against a broad spectrum of solid tumors where chemotherapy, radiotherapy and other targeted therapies have failed.
According to Dr. Erlinda M. Gordon, M.D., Medical Director of Epeius, "In advancing these new trials in the United States, we are keeping our promise to the Food and Drug Administration, who originally granted us permission to make Rexin-G available to foreign countries with the proviso that we would open clinical trials in the United States as soon as practicable. With more than three years of clinical experience with Rexin-G in an increasing number of otherwise intractable cancers in the Philippines, Japan and the US, we have gained valuable insights into the general safety, optimal dosing parameters, and best treatment regimens that provide the greatest benefits for the cancer patient without compromising safety. In addition, we have brought the formulation of Rexin-G to its highest clinical potency, enabling treatments of only two or three simple infusions per week."
The clinical trials of Rexin-G for breast cancer and sarcoma will initially be centered in San Marino, CA, where Epeius Biotechnologies Corp. has its headquarters, and in Santa Monica, CA at the Sarcoma Oncology Center. Dr. Sant P. Chawla, M.D., who trained at the University of Texas M.D. Anderson Cancer Center, is a renowned expert on malignant sarcomas, and has agreed to serve as Principal Investigator (PI) for both clinical trials. With the global demand for Rexin-G increasing, Epeius is actively engaged in the development of additional trials and the establishment of treatment centers in the United States and around the world. For further up-to-date information concerning the clinical trials, treatment options, and/or eligibility requirements, interested persons may contact Dr. Gordon at: emgordon@epeiusbiotech.com.
Pazopanib Shows Positive Results in Soft Tissue Sarcoma GlaxoSmithKline (GSK) announced on June 4th results from ongoing Phase II studies of pazopanib in soft tissue sarcoma (STS). The results were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The results observed with pazopanib support further investigations. Pazopanib is an oral, investigational angiogenesis inhibitor targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and c-kit, important proteins in the angiogenic process. Angiogenesis, which is the growth of new blood vessels in the body, plays a critical role in the growth and spread of tumors. The Phase II study evaluated the effect of pazopanib in patients with advanced STS who had failed prior therapy for advanced disease. Currently there is no standard treatment for such patients. Of 80 patients included in the first stage of this study, 27 (34%) achieved progression-free survival at 12 weeks. Pazopanib was evaluated in four types of STS in the first stage of the study: leiomyosarcoma, liposarcoma, synovial sarcoma and other soft tissue sarcomas. Pazopanib demonstrated activity in all tumor types except liposarcoma, and the study is ongoing to further investigate activity in the responsive tumor types. The most common adverse events recorded were hypertension, fatigue, hair color change, and nausea.
How Cancer Survivors Provide Support on Cancer-Related Internet Mailing Lists Internet mailing lists are an important and increasingly common way for cancer survivors to find information and support. Most studies of these mailing lists have investigated lists dedicated to one type of cancer, most often breast cancer. Little is known about whether the lessons learned from experiences with breast cancer lists apply to other cancers. The objectives of this study were to compare the structural characteristics of 10 Internet cancer-related mailing lists and identify the processes by which cancer survivors provide support. The authors studied a systematic 9% sample of email messages sent over five months to 10 cancer mailing lists hosted by the Association of Cancer Online Resources (ACOR). Content analyses were used to compare the structural characteristics of the lists, including participation rates and members’ identities as survivors or caregivers. The authors used thematic analyses to examine the types of support that list members provided through their message texts.
The Results were as follows. Content analyses showed that characteristics of list members and subscriber participation rates varied across the lists. Thematic analyses revealed very little “off topic” discussion. Feedback from listowners indicated that they actively modeled appropriate communication on their lists and worked to keep discussions civil and focused. In all lists, members offered support much more frequently than they requested it; survivors were somewhat more likely than caregivers to offer rather than to ask for support. The most common topics in survivors’ messages were about treatment information and how to communicate with health care providers. Although expressions of emotional support were less common than informational support, they appeared in all lists. Many messages that contained narratives of illness or treatment did not specifically ask for help but provided emotional support by reassuring listmates that they were not alone in their struggles with cancer. Survivors’ explicit expressions of emotional support tended to be messages that encouraged active coping. Such messages also provided senders with opportunities to assume personally empowering “helper” roles that supported self-esteem.
The authors Conclude: Many cancer survivors use the Internet to seek informational and emotional support. Across 10 lists for different cancers, informational support was the main communication style. The finding of an emphasis on informational support is in contrast to most prior literature, which has focused on emotional support. The authors found the most common expressions of support were offers of technical information and explicit advice about how to communicate with health care providers. Topics and proportions of informational and emotional support differed across the lists. Previous surveys of ACOR subscribers showed that they join the lists primarily to seek information; this qualitative study shows that they can and do find what they seek. They also find opportunities to play rewarding roles as support givers.
The Cancer Crusade was founded by spouses Roger and Kathy Cawthon who are both 11-year cancer survivors (renal cell carcinoma and breast cancer, respectively). Their mission is to help other cancer survivors and caregivers on their own cancer journeys by lighting their paths a bit, sharing what they have learned along the way, and reminding them that they are never alone. Their motto is “Fighting Cancer with Hope and Humor.” On the pages of their site you will find several “rooms,” each with its own special offerings. Take your time and explore the “Kitchen,” “Library” and “Meditation Room.” Add your name and/or the names of those you would like to the “Prayer Circle” page, who will be prayed for daily in a non-denominational prayer. Enjoy the world-famous Survivor Movie, have some laughs on the “Healing With Humor” page, explore the creative ideas on the “Healing Projects” page, visit the “Publications” page to subscribe to free monthly and weekly publications (and to download current issues), and shop in the “Gift Shop” where you will find gift ideas for survivors and caregivers alike.
young (cancer) spouses - Helping spouses copy with cancer YoungCancerSpouses’ mission is to bring together young spouses of adults with cancer to share information, support, and experiences. The needs of young spouses of cancer patients often go unrecognized and unappreciated. The emotional and logistical issues a young spouse of a cancer patient faces are vastly different from spouses of older cancer patients that dominated oncology units and support groups. General family support groups are likewise inadequate at addressing the needs of a young cancer spouse. At YoungCancerSpouses, they seek to provide a source of practical information gained from their experiences as young cancer spouses. They also strive to bring together other young cancer spouses to share ideas, lend support, and validate their wide range of feelings and emotions so they can find comfort in an understanding community. Some of the resources on their website include: Tips on Taking Care of Yourself, Practical Care Giving Tips for Your Spouse, Tips on Preparing for Medical Appointments including downloadable forums, and of course an Online Forum where spouses can reach out to each other.
Common Chemicals Pose Danger For Fetuses, Scientists Warn In a strongly worded declaration, many of the world's leading environmental scientists warned in late May that exposure to common chemicals makes babies more likely to develop an array of health problems later in life, including diabetes, attention deficit disorders, prostate cancer, fertility problems, thyroid disorders and even obesity. The declaration by about 200 scientists from five continents amounts to a vote of confidence in a growing body of evidence that humans are vulnerable to long-term harm from toxic exposures in the womb and during their first years.
Convening in the Faroe Islands in the North Atlantic, toxicologists, pediatricians, epidemiologists and other experts warned that when fetuses and newborns encounter various toxic substances, growth of critical organs and functions can be skewed. In a process called "fetal programming," the children then are susceptible to diseases later in life — and perhaps could even pass on those altered traits to their children and grandchildren. The scientists' statement also contained a rare international call to action. The effort was led by Dr. Philippe Grandjean of Harvard University and the University of Southern Denmark, and Dr. Pal Weihe of the Faroese Hospital System, who have spent more than 20 years studying children exposed to mercury.
Many governmental agencies and industry groups, particularly in the United States, have said there is no or little human evidence to support concerns about most toxic residue in air, water, food and consumer products. About 80,000 chemicals are registered in the United States. Yet the scientists urged leaders not to wait for more scientific certainty and recommended that governments revise regulations and procedures to take into account subtle effects on fetal and infant development.
Chemicals with evidence of developmental effects include compounds in plastics, cosmetics and pesticides. "Given the ubiquitous exposure to many environmental toxicants, there needs to be renewed efforts to prevent harm. Such prevention should not await detailed evidence on individual hazards," the scientists wrote in the four-page statement.
The scientists are particularly concerned that the newest animal research suggests that chemicals can alter gene expression — turning on or off genes that predispose people to disease. Although the DNA itself would not be altered, such genetic misfires in the womb may be permanent, and all subsequent generations could be at greater risk of diseases too. "Toxic exposures to chemical pollutants during these windows of increased susceptibility can cause disease and disability in childhood and across the entire span of human life," the scientists concluded.
In a more optimistic vein, the researchers said that if contaminants do play a big role in human health problems, some diseases could be prevented. "Reducing exposure would lead to tremendous benefits," said Dr. Bruce Lanphear, director of the Environmental Health Center at Cincinnati Children's Hospital Medical Center. "We shouldn't wait for an epidemic to fully mature before we develop policies to protect children."
For centuries, the basic rule of toxicology has been "the dose makes the poison." Now, the scientists say "the timing makes the poison" — in other words, when a toxic exposure occurs is as important as the amount people are exposed to. The fetus "is extraordinarily susceptible to perturbation of the intrauterine environment," they wrote. The growing brain is the most sensitive. Mothers' exposure to mercury and polychlorinated biphenyls (PCBs) in fish and other seafood can cause slight declines in a child's IQ and motor skills. In addition, early exposure to pesticides might trigger Parkinson's and Alzheimer's diseases.
Also, children exposed to lead, organophosphate pesticides or cigarette smoke have greater risk of attention deficit hyperactivity disorder. One of every three cases — or an estimated 560,000 children in the United States — can be attributed to lead exposure or prenatal tobacco smoke exposure, Lanphear reported in a study published in December. The immune, reproductive and cardiovascular systems also are vulnerable to early damage. Children exposed prenatally to PCBs have a high rate of infections and weak response to vaccinations. Many chemicals also can mimic hormones, and in animal tests, they feminize newborns, lowering sperm counts and promoting prostate, testicular, uterine and breast cancers.
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