VQD-001 clinical trial

VQD-001 is a clinical stage drug with a novel anti-tumor action that has potential as a treatment for cancer. VQD-001 has been safely used for more than 50 years as a treatment for leishmaniasis, a protozoan infection usually found in tropic and sub-tropic developing countries. It has been shown to be effective in breast, prostate, multiple myeloma, malignant melanoma, bladder, and colon cancer cell lines. Investigators at the Cleveland Clinic Taussig Cancer Center found that VQD-001 inhibits specific protein tyrosine phosphatases (PTPases) that are overexpressed in certain cancers. This overexpression plays an integral role in tumor growth in certain cancers. A Phase I/II study in patients with refractory cancers is underway at Taussig Cancer Center.

Protective action against kidney injury in myeloma

Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury

Akira Arimura, Min Li, and Vecihi Batuman

US-Japan Biomedical Research Laboratories, Tulane University F. Edward Hebert Research Center, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA, Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA

The most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as "myeloma kidney" that often progresses to end stage kidney diseases. Myeloma kidney is associated with a significant increase in all-cause mortality, yet no effective intervention, except a limited use of steroid, is available. Here, we report that PACAP38 dramatically prevents injury of cultured renal proximal tubule cells caused by myeloma light chains through suppression of proinflammatory cytokines production, by inhibiting p38 MAPK and translocation of NFB via both PAC₁- and VPAC₁-receptors. The suppressive effects of PACAP was as effective as dexamethasone in all of their cytokine assays, and demonstrated both in vitro and in vivo. Furthermore, PACAP38 inhibits myeloma cell growth directly and may also indirectly by suppressing production of the growth factor, IL-6, from bone marrow stromal cells, that is stimulated by adhesion of myeloma cells. These findings render PACAP38 worth evaluation as a promising candidate for an effective and safe renoprotectant in myeloma kidney, and possibly other nephropathy, and also as a new antitumor agent in multiple myeloma.

Akira Arimura^*, Min Li, and Vecihi Batuman

Protein ULBP2-BB4 has anti-tumor effect

A novel bispecific protein (ULBP2-BB4) targeting the NKG2D receptor on natural killer (NK) cells has potent antitumor activity against human multiple myeloma in vitro and in vivo

Department of Internal Medicine, Laboratory of Immunotherapy, University Hospital, Cologne, Germany

The inability of the immune system to recognize and kill malignant plasma cells in patients with multiple myeloma (MM) has been attributed in part to the ineffective activation of natural killer (NK) cells. In order to activate and target NK cells to the malignant cells in MM we designed a novel recombinant bispecific protein (ULBP2-BB4). While ULBP2 binds the activating NK receptor NKG2D, the BB4 moiety binds to CD138, which is overexpressed on a variety of malignancies including MM. ULBP2-BB4 strongly activated primary NK cells as demonstrated by a significant increase in IFN-g secretion. In vitro, ULBP2-BB4 enhanced the NK-mediated lysis of two CD138+ human multiple myeloma cell lines, U-266 and RPMI-8226, and of primary malignant plasma cells in the allogenic and autologous setting. Moreover, in a nude mouse model with subcutaneously growing RPMI-8226 cells, the co-therapy with ULBP-BB4 and human peripheral blood lymphocytes abrogated the tumor growth. These data suggest potential clinical use of this novel construct in patients with MM. The use of recombinant NK receptor ligands that target NK cells to tumor cells might offer new approaches for other malignancies provided a tumor antigen-specific antibody is available.

Elke Pogge von Strandmann, Hinrich P. Hansen, Katrin S. Reiners, Roland Schnell, Peter Borchmann, Sabine Merkert, Venkateswara R. Simhadri, Andreas Draube, Marcel Reiser, Ingvill Purr, Michael Hallek, and Andreas Engert

EMEA Reviews Revlimid

Celgene Corporation announced that the European Medicines Agency (EMEA) has accepted Revlimid (lenalidomide) for review. The application is based on clinical data from a Phase II trial of MDS patients.

Revlimid has been designated as an Orphan Medicinal Product in the European Union (EU) for the treatment of MDS.

Revlimid also has been designated as an Orphan Medicinal Product in the EU for treatment of multiple myeloma (MM).

Celgene expects to file its Drug Application for Revlimid in previously treated patients with relapsed/refractory MM to the FDA in 4Q 2005, and to the EMEA in 1Q 2006.

Cure cancer, join the grid

I've been a member of the World Community Grid for the past year. I encourage others to sign up.

Your computer's CPU sits idle most of the time when it's powered on, even when you're working. You can put that wasted CPU time to good use by joining the World Community Grid.

All the details are located at http://www.worldcommunitygrid.org/index.html

Who is World Community Grid?
The World Community Grid's mission is to create the world's largest public computing grid to tackle projects that benefit humanity. Its success depends upon individuals collectively contributing their unused computer time.

World Community Grid is making technology available only to public and not-for-profit organizations to use in humanitarian research that might otherwise not be completed due to the high cost of the computer infrastructure required. All results will be in the public domain and made public to the global research community.

How You Can Join
Making a difference has never been easier! Grid technology is simple and safe to use. To start, you download and install a small program or "agent" onto your computer. When idle, your computer will request data on a specific project from World Community Grid's server. It will perform computations on this data, send the results back, and ask the server for a new piece of work. Each computation that your computer performs provides scientists with critical information that accelerates the pace of research!

Ongoing Projects
Human Proteome Folding Project is advancing our knowledge of human disease. Identifying the proteins that make up the Human Proteome may help scientists build novel and effective treatments for diseases like cancer, HIV/AIDS, SARS, and malaria.

Dana Farber Boston Marathon challenge

A good friend, Dr. Joel Rothaizer, is running in the upcoming Boston Marathon to raise money for the Dana Farber Cancer Institute, a world-leading Multiple Myeloma research site.

He is running in memory of his mother Harriet, whose life was cut short by Multiple Myeloma.

When I was originally diagnosed in 2002, I visited the Dana Farber Institute for a 2nd opinion. It is a marvellous cancer center, staffed with caring and knowledgeable people. For me it was a beacon of hope.

It is an excellent place to donate funds. It is a simple as following this URL:

https://www.kintera.org/faf/donorReg/donorPledge.asp?ievent=113292&lis=1&kntae113292=76215443D8294D599C9F6A57441F608C&supId=98437596

Here is Joel's note:

I'm excited to be running the Boston Marathon on April 17th. I'm equally excited to be participating in the Dana-Farber Marathon Challenge, supporting the Dana-Farber Cancer Institute's goal to find better therapies, and ultimately, cures for cancer.

100% of the funds raised go to a program that enables gifted young scientists at the leading edge of discovery to achieve better cure rates and to enhance patients' quality of life.

I've set a goal of collecting $26,200, or $1,000 for each mile that I run. I hope you will support my challenge by giving a gift and, in doing so, help bring an end to the challenge of cancer.

I'll be running in memory of my mother, Henrietta Rothaizer, who died of multiple myeloma at far too young an age, and carrying her picture. I'll be delighted to carry the names and/or pictures of any of your loved ones. This can be because they're currently being treated for cancer, already departed, or for any other reason that touches your heart.

Please consider giving generously to this great cause. And wish me luck! This has been a dream of mine.

Warmly,
Joel

Cancer predisposition - is it in your genes?

Research results published in The Lancet http://www.thelancet.com/ show an interaction of genes and the protective effects of eating cruciferous vegetables. This is based on a study of inhabitants of central and eastern Europe, a region which has traditionally had a high rate of cruciferous vegetable consumption.

Cruciferous vegetables such as cabbage, broccoli, and brussel sprouts contain potent anti-cancer compounds known as isothiocyanates. Isothiocyanates are thought to be eliminated by glutathione-S-transferase enzymes, which are produced by GSTM1 and GSTT1 genes. Individuals who have the inactive form of either or both genes, result in no enzyme being produced, and should therefore have higher isothiocyanate concentrations because of their reduced elimination capacity. Since the isothiocynates concentrations are higher, this might result in a greater anti-cancer effect.

According the Lancet article, researchers found that people with an inactive GSTM1 gene were 33 percent less likely to get lung cancer if they ate cruciferous vegetables weekly. In people with an inactive GSTT1 gene, there was a 37 percent protective effect and when both genes together were inactive the increase was a 72 percent effect.

They found no protective effect in people with active forms of both genes.

However, there are been many other published articles about the anti-cancer effects of eating all vegetables, including cruciferous vegetables, so they should definitely be part of an anti-cancer diet.

Mapping the human genome

Scientists have completed the first catalogue of common genetic differences between four of the world's ethnic groups.

The Haplotype Map marks a historic step toward the era of customized health care -- in which treatments could be tailor made to a patient's gene type.

Using the DNA of 269 people from China, Japan, Nigeria and the U.S., the project has essentially compiled a new map of the human genome.

This one organizes the book of life encoded in human DNA into paragraphs -- known as haplotypes -- that make it exponentially easier to spot genetic mutations.

For example, the Hap Map has discovered nearly four million mutations and of those, roughly 100 appear in extreme frequency in one group more than another, such as with the lactase gene type of Europeans that allows the lifetime digestion of dairy products, and the mutation that protects sub-Saharan Africans from malaria.

"This helps us to see which genes mattered to the evolution of our species," said Harvard Medical School's David Altshuler, lead author of the Hap Map report also published today in the journal Nature.

In 2001, researchers at the University of Toronto and the Massachusetts Institute of Technology were working on a bowel disease study with 200 Ontario families and discovered the whole genome seems to be arranged in this same block pattern -- like paragraphs in a text.

It seems parents pass down their chromosomes to children in these particular chunks. As well, genetic mutations seem to turn up in the same places in those chunks -- even in different families -- like a library where every book has a typo in the first paragraph of its third page.

In October of 2002, researchers launched the Hap Map that, like an index, would catalogue these blocks and their common mutations in diverse ethnic groups to ensure the haplotype pattern applied broadly.

This way, scientists would no longer have to scan a whole book for a typo, but simply flip to a specific page.

The result is leading to large-scale genetic studies never before possible.

In Canada, researchers are studying 2,500 Ontario residents in the world's largest hunt for genes that increase the risk of colon cancer.

In Britain, thousands of patients are being enrolled in gene studies of eight common conditions -- including heart disease.

A U.S. group has already relied on the Hap Map, which has been uploaded to the Internet as the data came available, to find the gene mutation that increases the risk of macular degeneration, the leading cause of vision loss in the elderly.

Polio reported in Minnesota

If your shots are out-of-date owing to a stem cell transplant, read on.
***
From the Minnesota Department of Health http://www.health.state.mn.us/news/pressrel/polio101305.html

Three additional cases of polio virus infection have now been identified in central Minnesota, according to officials at the Minnesota Department of Health (MDH).

Three children – all members of the same family – have now been found to be infected with the virus. MDH disease investigators say there are direct links between the family of the three children and the family of an infant found to be infected with the virus at the end of September.

The two families are not related by blood.

Like the infant, the three children do not have any symptoms of paralytic polio – and like the infant, they had not been vaccinated against the illness.

The affected families are members of the Amish community in central Minnesota. Health officials are working with the Amish community to identify people who may have been exposed to the virus – and make sure people who may be at risk have been immunized against polio.

The three new cases were identified through efforts by local, state and federal public health officials to follow up with people who may have been exposed to the virus.

“These cases do not represent a generalized outbreak of polio virus infection,” said Minnesota Health Commissioner Dianne Mandernach. “You are not at risk of infection unless you have had close contact with an infected person, and you have not been immunized against polio. The general public is not at risk.”

MDH has been focusing its disease investigation on the Amish community, and on health care workers who may have provided care to the infected infant, according to Dr. Harry Hull, Minnesota State Epidemiologist.

“We will continue to follow up directly with people who may have been exposed to the virus,” Dr. Hull said. “Unless you are contacted directly by a health care or public health worker, you are not at any risk of infection in connection with these cases.

“However, these cases do serve to underscore the importance of making sure your immunizations are up to date for polio and other vaccine-preventable diseases,” Dr. Hull added.

Because members of the central Minnesota Amish community have links with Amish groups in other parts of the country, it’s possible that cases of infection may eventually be identified outside Minnesota, Dr. Hull said.

MDH officials say the virus strain found in the four central Minnesota cases appears to be a variant of the strain used in oral polio vaccine, which is still used in some parts of the world – but not in the U.S.

Use of the live-virus oral vaccine was discontinued in the U.S. in 2000. All polio vaccinations in the U.S. are now done with an injected, killed-virus vaccine.

Before use of the live-virus vaccine was discontinued, it caused about eight cases of paralytic polio a year in the U.S., on average. The last case of naturally occurring polio in the U.S. was reported in 1979. Naturally-occurring polio is considered to be eradicated in the western hemisphere.

Paralytic disease is relatively uncommon in people who are infected with the polio virus, occurring in only about one of every 200 people infected.

Rapid Restoration Of Immunity In Immune-suppressed Cancer Patients Using T-cell Vaccines

As someone who waited three years after transplant for immunizations, including pneumococcus, I was very impressed by the following two posts relating to this advance.

***

Patients with multiple myeloma suffer from a malignant proliferation of plasma cells in their bone marrow. The standard treatment for this form of cancer is high-dose chemotherapy and transplantation of one's own blood-producing adult stem cells; however, this aggressive treatment wipes out the mature immune-system cells of patients -- leaving them vulnerable to infection.

A complementary treatment currently approved is to vaccinate myeloma patients against pneumococcus, a common bacterial infection, a year after their transplantation. But why wait a year, wondered researchers at the University of Pennsylvania School of Medicine? Their own investigation revealed that protective levels of immunity against pneumococcus could be obtained in patients who were given the prophylactic bacterial vaccine in addition to a new autologous T-cell-based vaccine only two weeks after transplantation. Indeed, protection developed in the patients within a month after the transplantation. Their clinical trial is described in this week's online edition of Nature Medicine.

"We found that we can rapidly rebuild the patients' immunity after chemotherapy and stem-cell transplant," said Carl June, MD, Director of Translational Research at Penn's Abramson Cancer Center. "For future studies, we will apply the principles learned from this study to hone the development of a cancer vaccine aimed directly at tumors and other cancers," added June, who is also Professor of Pathology and Laboratory Medicine in Penn's School of Medicine.

Early Measures Prove Highly Effective
Patients in the study were all given two pneumococcal vaccines one month and three months after their stem-cell transplants; whereas normally they would have to wait up to a year. The patients were then divided into four groups: one group received an initial pneumococcal vaccine before transplantation and chemotherapy, then a T-cell vaccine immediately after; a second group received the pneumococcal vaccine before transplantation and chemotherapy, but received the T-cell vaccine three months after their transplant and chemotherapy. The last pair of groups did not get the initial pneumococcal vaccine before the standard transplant and chemotherapy, but did receive the T-cell vaccine immediately after or three months after the standard treatment.

The researchers found that the patients in the group that received the early pneumococcal vaccine plus the early T-cell vaccine infusion had an immune response that was protective and higher than often achieved in normal patients who do not have cancer.

Custom-Designed T-Cell Therapies Will Enhance Immunity
At the recently opened Clinical Cell and Vaccine Production Facility at Penn, "we have been using new cell-based custom therapeutics derived from a patient's own T cells in this and other studies, with the long term goal of improving outcome and extending life," explains co-author Bruce Levine, PhD, who directs the Facility. T-cells are taken from a patient and expanded about a thousand fold. The engineered T-cells are then given back to the patient a few weeks later via an infusion. The newly grown T cells continue to grow in the patient, which is different than a red blood cell transfusion. The effect of this therapy is to quickly repopulate a patient's immune system with mature cells that can support immunity against infections, and potentially against tumors.

"This study showed how to take a vaccine that is a failure in people after chemotherapy and to modify it so that it works in cancer patients after chemotherapy," says June. "The surprising thing is that the vaccine works better than normal in many of the patients. This is the first step in developing a new form of personalized therapy for the treatment of cancer, where engineered T-cells will be used to boost the immune system, essentially priming it to make cancer vaccines work better."

In addition to June and Levine, study co-authors include Edward Stadtmauer from Penn and Aaron Rapoport and Alan Cross, University of Maryland.

Immunotherapy effective after chemotherapy

Results from a study funded primarily by the Leukemia & Lymphoma Society demonstrate that a patient's immune system, crippled by chemotherapy, can be rapidly rebuilt using the patient's own cells.

Researchers at the University of Pennsylvania School of Medicine and the University of Maryland are reporting the successful results of their clinical trial of "immunotherapy" in this week's online edition of Nature Medicine.

The "proof-of-principle" study was focused on multiple myeloma patients and is the first-ever successful adoptive immunotherapy trial.

"This is the first randomized study to demonstrate accelerated T cell reconstitution, and the first demonstration of improved immune function," said Deborah Banker, vice president, Research Communications for the Society.

Variations on the immunotherapy theme are being tested around the world, offering the promise of using a patient's and/or a donor's immune system cells to selectively kill malignant cells with minimal side effects. But, real proof that immunotherapy can work has been elusive.

The short-term benefit of the researchers' procedure will likely be the reduction in post-transplant infections, which are suffered by as many as 40% of transplant patients. Their findings also support the further development of immunotherapy to induce effective anti-tumor immune vaccine responses that could eradicate minimal residual disease and lead to cures.

Melphalan, Prednisone & Thalidomide in newly diagnosed MM patients

The combination of melphalan, prednisone, and thalidomide produced a quick and lasting response in newly diagnosed multiple myeloma patients, according to a study published in the journal Cancer .

Melphalan, prednisone and thalidomide are established treatment options for multiple myeloma. The effect, however, of combining these three drugs is unknown. Researchers in Italy describe treatment outcomes for 49 newly diagnosed multiple myeloma patients who were treated with a combination of MPT:

• 24% of patients achieved a complete or near-complete disappearance of myeloma.
• 49% of patients achieved a partial disappearance of myeloma.
• 6% of patients did not respond to treatment, and myeloma worsened in 10% of patients.
• The median time to maximum treatment response was four months.
• 91% of patients survived for at least two years.
• Common adverse effects of treatment with MPT included abnormal blood cell counts (22% of patients), blood clots (20% of patients), and infections (12% of patients).
• One patient died of a pulmonary thromboembolism (a blood clot in the lungs).

The researchers conclude that treatment of multiple myeloma with MPT merits further investigation in randomized clinical trials. Response to this combination of drugs appears to be good, though treatment with an anticoagulant may be necessary to prevent blood clots.

Patients with multiple myeloma may wish to talk with their doctor about the risks and benefits of participating in a clinical trial further evaluating therapeutic options.

Reference: Palumbo A, Bertola A, Musto P et al. Oral Melphalan, Prednisone, and Thalidomide for Newly Diagnosed Patients with Myeloma. Cancer. 2005;104:1428-33.

IMF honors Dr. David Agus

The International Myeloma Foundation -- conducting research and providing education, advocacy, and support for myeloma patients, families, researchers, and physicians -- announced Oct 20, it is singling out for honors David B. Agus, M.D., a nationally prominent researcher at Cedars-Sinai Medical Center in Los Angeles, for his cutting edge research to help determine which patients respond best to treatments for cancer.

By using some of the world's most powerful superconducting magnets to separate the proteins in a drop of blood, Dr. Agus is engaged in a breakthrough study to help determine which myeloma patients are best able to benefit from bone marrow transplants, a mainstay of myeloma treatment. The data Dr. Agus is able to retrieve from a single droplet of blood is so vast that a bank of super computers is employed to help analyze the results.

"Others look at cancer and ask why, but I look at my patients and ask who -- who will benefit, whom can we help," said Dr. Agus. "To me it is exciting to take this very advanced technology that combines magnets and super computers, and then using 'machine-learning' we are able to solve these very human problems."

For his work in myeloma, Dr. Agus has teamed with The International Myeloma Foundation Chairman, Brian G. M. Durie, M.D., a member of the medical staff at Cedars-Sinai, who is principal investigator of this study for the Southwestern Oncology Group (SWOG).

"We do know that myeloma patients can have dramatic benefits from their treatments, but the relapse rate is 13 percent per year, and that's too high," said Dr. Durie. "We are pleased that Dr. Agus has agreed to use his highly technical skills and very advanced resources at Cedars-Sinai to help us target treatments to individual patients so they will benefit from what we do." Adds Dr. Agus, "The International Myeloma Foundation persuaded me on behalf of their patients that this is a crucial area for research, and I am pleased to partner with them on this new frontier of personalized medicine."

Also being honored this year is the Affymetrix Corporation that helped develop "gene chips," vast amounts of biological data on a small glass slide to study the role of genes and their components.

The theme of The International Myeloma Foundation's gala will be "Lights, Camera, Cure!" Robert Klein -- actor, comedian, director, composer and author -- will provide the Gala's featured entertainment. Master of Ceremonies will be television host Robin Leach. All proceeds from the gala benefit programs instituted and sponsored by The International Myeloma Foundation, including scholarship and research grants, and advocacy and seminars for patients, family members and medical professionals. More information about the Gala can be found at http://www.myeloma.org/.

Cancer crisis looming: all talk no action

As the number of cases rise, the future of cancer care is caught up in a debate between the federal government and a coalition of experts over spending strategy

OTTAWA -- Lawrence Smith doesn't mince words when he predicts the future of Canada's cancer care system.

The 69-year-old retired lawyer was diagnosed with prostate cancer earlier this year, underwent drug therapy and radiation, and has nothing but praise for the treatment he received. But he's worried that as the number of cancer cases grows in coming years, others won't be so lucky.

"They are going to be overwhelmed," he says of health-care professionals.

"And the thing that I'm concerned about is that the country is not going to be prepared to pay for the medical care it demands."

He says Canada must respond to the gravity of the situation with solutions ranging from an innovative cancer plan to, if necessary, private health care.

Smith is one of 149,000 Canadians diagnosed with cancer this year. To these people, the state of the country's cancer system is crucial -- in many cases, the difference between living and dying.

But the future of cancer care is caught up in a debate that has pitted the federal government against a coalition of the country's cancer experts.

The experts have developed a detailed cancer control plan and have asked the federal government to spend $260 million over five years on a strategy that would help provinces co-ordinate strategies, share information and set cancer control targets. The money would also establish clinical practice guidelines that outline proven ways to improve cancer care, create a database and plan to deal with the shortage of cancer care workers, and improve the palliative care provided to dying patients.

The strategy would be implemented by a council that would include federal representatives as well as experts from the provincial cancer agencies, the Canadian Cancer Society and a national advocacy network for cancer patients.

Prime Minister Paul Martin's government has instead opted to spend $300 million over five years on an "integrated disease strategy" that attempts to persuade Canadians to lead healthier lives, thereby reducing their risk of getting three diseases -- cancer, heart disease and diabetes.

Much of that money will be allocated to programs designed to attack all three diseases, but part of the $300 million will be directed to "disease specific" efforts -- $90 million for diabetes, $59.5 million for cancer and $18.9 million to develop a cardiovascular disease "action plan."

The rationale for an integrated approach is that different chronic diseases can often stem from the same causes, such as smoking, obesity and a lack of exercise. Better to attack them with a joint campaign, says the government.

That decision has frustrated experts like Dr. Simon Sutcliffe, a longtime cancer physician and president of the B.C. Cancer Agency, who heads the coalition behind the proposal.

He supports the federal strategy's emphasis on health promotion, but says that only deals with part of the problem. A comprehensive strategy must also include ways to better treat patients who already have cancer, he says.

"We have provinces that have cancer screening programs that are widely adapted within their populations, and in other provinces we do not. Waiting times for procedures vary considerably across the provinces. Drugs on formularies (that are publicly insured) vary from province to province. The use of guidelines for accepted or best practices are variably taken up across the provinces. Standards differ on how chemotherapy is practised, prescribed and administered. There are very great differences in terms of guidelines for good palliative care."

Without a national strategy to ensure a more even level of care, he says, Canadians in future years will be confronted with a horrible dilemma.

"You'll have a perverse situation that you might decide where you want to live based upon how big you think your cancer risk is and what sort of approach you think the province might take to your health care."

Dr. David Butler-Jones, the country's chief public health officer and head of the Public Health Agency of Canada, acknowledges the threat of cancer caseloads.

"Every year we don't make the investments we need in prevention is another year lost and a bigger hole to try to fill," he says. "The lineups just get longer and they're going to get longer.

"At the end of the day, we could triple the resources we spend on cancer and it would not be enough in a couple of decades down the road."

Butler-Jones says an integrated strategy is best able to battle the common "underlying risk factors" that increase someone's odds of getting cancer, heart disease or diabetes.

"If we focus only on one aspect, we actually risk the health of the population because often we risk not making the best use of whatever resources we have."

The federal strategy's $59.5-million allocation for cancer will be spent in areas such as: public education about cancer risks such as exposure to the sun; Internet sites to give patients information about the "complexities" of cancer treatment; improved registries and databases on the extent of cancer in Canada; and a federal pledge to "champion a pan-Canadian process" to encourage more co-operation among cancer experts so that standards and guidelines can be developed.

Butler-Jones says the coalition's proposal is flawed because, while it includes the support of provincial cancer agencies, it may not necessarily have the backing of cabinets in those jurisdictions.

"We can't just as a federal government just adopt it. Because we're in a partnership here with the provinces and territories. They deliver these programs."

Butler-Jones says the only way to get "durable" results is through a plan developed with the provinces.

Health Minister Ujjal Dosanjh notes Canada is already spending more than $100 million on cancer research and has pledged to shorten waiting times for treatment of the disease.

He pays tribute to the "huge reservoir of energy" among the cancer experts, but he's not convinced their approach is better than the government's.

"If you're talking about clinical common guidelines for clinical practice in cancer -- for that, you don't have to have a stand-alone cancer strategy. You could do that as part of the overall strategy, the integrated disease strategy. If there is a place for federal leadership on these issues, I think that can be accommodated within the context of that strategy."

In May, the World Health Organization warned of a "cancer epidemic" and urged countries to implement comprehensive cancer control programs that include strategies for prevention, early detection, diagnosis, treatment, rehabilitation and palliative care.

"Efforts to prevent and control cancer are hampered by the low priority frequently given to the disease by governments and health ministries, excessive reliance and expenditure on treatment, and a considerable imbalance between resources allocated for basic cancer research and those devoted to its prevention and control," WHO said.

Dr. Jean Lariviere, a former federal public servant who spent many years as a senior medical adviser within Health Canada and who represented Canada at the World Health Organization, helped lay the the groundwork for that resolution.

Lariviere has doubts about the merits of battling cancer through an integrated -- or "mainstreaming" -- approach.

"By trying to do everything, you end up doing nothing. If it is mainstream, it means that everything is of equal importance, which means people stop listening."

Peter Boyle, director of the WHO's International Agency for Research on Cancer, notes that countries like Britain and France have made great strides forward with cancer plans that set goals and targets to reduce cancer rates of incidence and mortality, and improved the quality of life for patients.

"It brought everyone together -- the people treating cancer, the basic researchers trying to understand cancer, the social scientists trying to change people's lifestyles to reduce the risk of cancer, patient groups, administrators, politicians."

Michael Decter, one of this country's most prominent health-care experts, agrees it makes sense to battle cancer through a "disease-specific" plan because "people identify with the disease they have, not with broad integrated things.

"I'm totally with the advocacy groups," says Decter, who was appointed in 2003 by the federal government and provinces to chair the Health Council of Canada, the independent advisory body that monitors medicare. "I'm absolutely convinced it's the right way to do this."

Decter says the council has not examined the cancer strategy, but his personal view is that the cancer system is unique and requires unique approaches.

Barbara Whylie, chief executive officer of the Canadian Cancer Society, says it's hard to understand why the government is "dragging its heels." She says it is an "embarrassment" that Canada is currently playing host to an international conference on combatting cancer while it lacks a comprehensive program itself.

"We already know that the cancer care system is straining at the seams," Whylie says. " We know that, from time to time, people have to be sent out of country or from province to province to get care. That's already happening. Every year that passes, that challenge is just going to grow and multiply if we don't do something now to try to deal with it."

Just a few kilometres away from Parliament Hill, Dr. Hartley Stern, a cancer doctor for 22 years and the senior administrator at the Ottawa Hospital Regional Cancer Centre, shakes his head in amazement at the lack of progress on such a critical public policy.

What's needed, he says, is federal leadership. Cancer control must become a priority.

"The case can be made simply on bang for your buck. If you're going to make an investment as a government and see some value added for society, cancer is a very good bet."

For instance, Stern says the federal government could introduce "tied funding", forcing the provinces to spend the money in areas such as improved cancer screening programs and palliative care.

If politicians don't act, Stern says, they will likely be forced by the thousands of Canadians who, in the years ahead, are told they have cancer.

"I think there is hope. It will come from the public just finally saying, 'This revolts me and I cannot tolerate this, and I will not vote for this government if they don't change their ways.' I don't know when, but I think that time is coming."

© The Edmonton Journal 2005

Clinical trials monitor

View muliple myeloma clinical trials at http://www.myelomatrials.org

Cancer tidal wave looms over Canada

From today's newspaper. Our cancer tsunamai is largely ignored by politicians.
***
'Spectacular success' in treating some cancers overshadowed by rising number of cases

OTTAWA -- Canada is lurching toward a crisis in cancer control and there is a "real and present danger" the country's health-care system will not be able to afford treatment for the tidal wave of patients who will get the disease in the decades ahead, says a major new report.

The warning is contained in a blueprint for action on a national cancer strategy prepared by the country's cancer experts.

The document, obtained by CanWest News Service, is more than five years in the making and has been presented to the federal government. It outlines how Canada's aging and growing population will create a steady rise in the number of people who get cancer and who die from the disease.

"Cancer has an ever-expanding impact on the lives of Canadians and on the economic interests of the country," says the report. "Yet, Canada is falling behind other developed countries in meeting this growing cancer burden."

There will be a "significant increase in the number of new cancer cases," says the report, adding this spike in demand for medical services "will cause inflationary pressures and put the sustainability of the health-care system at risk."

WILL BECOME NO. 1 KILLER

This year, it's estimated that 149,000 Canadians will be diagnosed with cancer -- 3,500 more than last year. As well, 69,500 Canadians will die of the disease -- 1,200 more than last year.

On the basis of current trends, 38 per cent of Canadian women and 44 per cent of men will develop cancer during their lifetimes. As well, 24 per cent of women and 29 per cent of men will die from cancer.

Within the next five years, it will replace cardiovascular disease as the No. 1 killer in Canada.

Dr. Simon Sutcliffe, president of the B.C. Cancer Agency, says the most frequent question he gets by the driver when gets into a taxi is: "So, you're a cancer doc. How are are we doing?"

The answer is always the same: The glass is half full and half empty.

In recent decades, there has been "spectacular success" in lowering mortality rates for some diseases, such as Hodgkin's disease, testes cancer, childhood cancers and breast cancer.

"It's been due to improvements in radiation therapy, combination chemotherapy, introduction of new drugs, bone marrow transplantation, hormonal therapies. A whole raft of things have brought incremental improvements over time."

But, Sutcliffe says, that doesn't diminish the fact more people are getting the disease and dying from it than ever before, because of our aging and growing population.

COSTS WILL BE STAGGERING

"I think the demographics are so mind-numbing that people just throw up their hands and roll their eyes and say, 'It's too big to do anything about.' And yet, the reality is it isn't too big to do anything about. There is tremendous power to influence this problem."

Sutcliffe is a senior member of a coalition of experts pushing for a national strategy on cancer control. The coalition's report, prepared by experts ranging from provincial cancer agencies to researchers to the Canadian Cancer Society, projects costs over the next 30 years that are staggering

They include $176 billion in direct health-care costs for cancer patients; $540 billion in lost wage-based productivity as cancer patients temporarily or permanently leave their jobs; and $248 billion in lost tax revenues because those patients are off work.

The coalition is calling for a $260 million, five-year plan that would provide more consistent care nationwide in areas such as screening programs to catch the disease in its early stages; clinical practice guidelines on the most up-date treatment; the types of drugs that should be publicly insured; standards on how chemotherapy is practised, prescribed and administered; and guidelines for palliative care.

The government, however, plans to treat cancer as part of an "integrated disease strategy" with a $300 million, five-year plan that attempts to persuade Canadians to lead healthier lives, reducing their risk of getting cancer, heart disease and diabetes.

On Sunday, cancer control experts begin meeting in Vancouver at the first international conference on strategies for fighting the disease, which the World Health Organization says kills six million people worldwide annually.

In Canada, there are millions of aging baby boomers who are entering the danger zone. This year, 44 per cent of new cancer cases diagnosed will occur in people over the age of 70; 25 per cent of cancer cases will come in those aged 60 to 69; 18 per cent will occur in those aged 50 to 59.

This increased cancer rate with age is probably due to a combination of increased and prolonged exposure to carcinogens and a weakening of the body's immune system.

While there have been improvements in survival rates for some types of cancers, in total, cancer still kills nearly half of its victims.

The coalition's report notes that cancer takes the lives of more people in Canada than strokes, respiratory disease, pneumonia, diabetes, liver disease and HIV/AIDS combined.

Getting through the next three decades -- as the bulge of aging baby boomers gradually reaches a peak and then levels off -- will be more difficult than many might imagine. Productivity throughout the Canadian workforce will be severely hampered.

Over the next 30 years, an estimated 2.4 million Canadian workers will get cancer and 872,000 of them will die of it.

All this will have a dramatic impact on economic growth and the ability of governments to raise sufficient revenues to properly treat cancer patients, warns the report.

"There exists the real and present danger that the increasing cost of health care and the higher volume of cancer cases will place severe pressures on the sustainability of the health-care system in Canada."

The report says the current cancer system is already undermined by "serious and ongoing cancer workforce shortages" that "threaten patient safety and service quality (and) generate longer wait times."

Federal-provincial showdown

The fight against cancer figures prominently in a potential political showdown brewing between Prime Minister Paul Martin's government and the provinces.

At the top of the agenda this weekend at the annual meeting of Health Minister Ujjal Dosanjh and provincial health ministers is whether the provinces will fulfil their pledge -- made when they were given $41 billion in federal funds last year -- to devise standards by Dec. 31, 2005 for how long patients should have to wait for key medical services, including cancer. Provinces are suggesting they might not make that deadline and that, ultimately, standards might vary from province to province.

But Martin and Dosanjh have declared they expect provinces to deliver on their pledge. With a federal election sometime in the next few months, it's critical for the Liberals that voters are assured waiting lists will get shorter -- not longer.

For cancer, however, the harsh truth is that rising caseloads will make it increasingly challenging to provide quality care.

Terry Sullivan, chief executive officer of Cancer Care Ontario, the provincial government's cancer advisory agency, says the growth of cancer cases is like a "slow epidemic" -- making it different from other health threats, like bird flu, that grab attention.

"This is not a sudden threat," Sullivan says. "This is a certain threat. "

"More people will have died of cancer in Ontario from the time you and I got up this morning than have died from avian flu, SARS and West Nile Virus to date.

"That's why it's more like a glacier moving slowly with a destructive force. It's not an avalanche, but it's a certain force moving forward in time."

© The Edmonton Journal 2005

Screening of FDA-Approved drugs

The MMRF is pleased to award

• David Frank, MD, PhD, Dana-Farber Institute
• Suzanne Lentzsch, MD, PhD, University of Pittsburgh
• Aaron Schimmer, MD, PhD, FRCPC, Princess Margaret Hospital

with $100,000 grant awards to support the testing of existing drug libraries against known molecular targets in myeloma. Using advanced screening technologies, researchers will identify compounds from these libraries that interact with known myeloma targets -- an important first step in developing these compounds into viable treatments for patients with myeloma.

Currently, there are many libraries of FDA-approved drugs and other available compounds that may be effective in treating multiple myeloma. However, to date, none of these libraries has been evaluated to determine their activity in treating myeloma.

To facilitate data sharing, the MMRF is maintaining a central database of all research results. The MMRF will also convene a Research Roundtable in early 2006 to enable researchers to share consistencies of findings and identify next steps toward validating potential new therapies for myeloma.

(From the MMRF Newsletter, Fall 2005)

Health strategy falls short of cancer group's funding goal

Once again the Canadian government lets the public down rather than showing leadership. The paltry $59M earmarked for cancer control over the next five years, is less than that pledged by the Canadian government for the tsunami, Hurricane Katrina and Pakistan earthquake relief.

In reading the news release it seems that the money will be used to lecture Canadians over diet and exercise. This is basically useless information. You'd have to live in a cave to have not heard the message about diet and exercise.

The government has ignored the useful information provided by the Canadian Institute for Cancer Control, which can be reviewed at http://www.cancercontrol.org/
***
OTTAWA - The federal government will spend $300 million over the next five years as part of a strategy to combat major chronic diseases cancer, heart disease and diabetes.

The details of the announcement, to be released today by Health Minister Ujjal Dosanjh, reflect his department's plan to reduce preventable diseases with an "integrated approach" that fosters health promotion.

However, in clustering the three diseases under a single strategic umbrella, the announcement is likely to disappoint cancer experts who had spent several years designing a national cancer control plan.

They had urged the government to spend $260 million over the next five years on a comprehensive cancer strategy to be implemented by a new council composed of cancer experts drawn from the government, provincial cancer agencies, the Canadian Cancer Society and various patients' advocacy groups.

Instead, out of its $300-million strategy, the government has set aside only $59.5 million exclusively for the cancer control initiative, to fall under federal responsibility.

Federal officials said Wednesday, however, that efforts to reduce cancer incidence and improve treatment of the disease will also be bolstered by other elements in the integrated strategy designed to jointly combat all three major chronic diseases.

"This new funding will address healthy eating, physical activity and healthy weights -- the key risk factors for some of the leading, preventable chronic diseases," says a news release to be issued today.

The federal release says that better diet, regular exercise and proper body weight can "protect against many chronic diseases," including cancer, heart disease and diabetes.

"Because major chronic diseases share common risk factors, an integrated approach is the most effective and practical way to seek to prevent these diseases and to advance health promotion," says Dr. David Butler-Jones, Canada's chief public health officer, in the news release.

The government says its strategy still allows for "disease-specific approaches where applicable."

However, Conservative MP Steven Fletcher said the new strategy falls far short of what is required to combat cancer and that the government should have adopted the proposed cancer program strategy developed by experts who spent a number of years developing it.

"The federal government is pooh-poohing it as if it is some high school project," he said.

"And yet their own approach is a half-cocked strategy for public appearances."

© The Edmonton Journal 2005

DNA samples sought from blood cancer victims

By Anita Srikameswaran, Pittsburgh Post-Gazette Genetic experts want people with a kind of white blood cell cancer to take their DNA to the bank. Representatives from "Bank on a Cure," an initiative of the International Myeloma Foundation, will be attending tonight's regular meeting of Multiple Myeloma Pittsburgh at 7 p.m. in The Western Pennsylvania Hospital-Forbes Regional Campus, Monroeville. Researchers will use the bank to look for genetic patterns that might help predict how patients will respond to specific treatments and their risks for certain side effects. Support group members and other myeloma patients are invited to contribute DNA samples to the project, which began about 18 months ago, said Dr. Brian Van Ness, co-director of Bank on a Cure and the head of the genetics, cell biology and development department at the University of Minnesota. "We're aiming for about 10,000 patient samples," he said, noting about 3,500 samples have been collected. "Every sample counts." Most of the samples have been provided by individuals who requested the test kit at the foundation's Web site www.myeloma.org. Kits contain store-brand mouthwash and a brief survey. Patients rinse their mouths with the wash, collect the liquid and send it to the researchers. All patient information is kept confidential and barcodes are used to label samples, he added. Many people must participate if researchers are to see the overall genetic patterns that might have an impact on the disease. For more information about Bank on a Cure, go to www.myeloma.org or call 1-800-452-2873. Copyright ©1997-2004 PG Publishing Co., Inc. All Rights Reserved.

Immunizations post transplant

In my case, three years after my allogeneic transplant and well over a year after discontinuing my Cyclosporine (anti-rejection medication), I finally spent the past few months bringing my "shots" up-to-date.

Here's what they've given me:

June 2005 - 4 shots

• Diptheria/Tetanus (DT)
• Killed Polio (IPV)
• Hepatitis B
• Haemophilus Influenza type B (HiB)

July 2005 - 4 shots

• Diptheria/Tetanus (DT) again
• Killed Polio (IPV) again
• Hepatitis B again
• Meningococcal C

October 2005 - 3 shots

• Influenza
• Meningococcal P
• Pneumococcal P

Now I'm scheduled in December for a booster Hep B and booster T/D.

They are going to check with the physician to determine whether I should have MMR - Measles, Mumps, Rubella.

Multiple Myeloma bracelet - only a buck each

http://www.myeloma.org/main.jsp?source=link&source_link_id=1834&type=article&tab_id=1&menu_id=0&id=1555

IMF Myeloma Bracelet - Imagine Moving Forward Imagine Moving Forward is the theme of the IMF’s new myeloma bracelet. Wear one in honor, celebration, or in memory of a loved one, and when people ask you what it’s for, it’s a perfect opportunity to spread the word about multiple myeloma. "Imagine Moving Forward" is on one side of the bracelet and "www.myeloma.org" is on the other. They’re only $1 each in sets of 10, so you can order one for everyone in your family. You can order yours today on our web site. To order by phone, please contact Rolake Bamgbose at (800) 452-2873 or RBamgbose@myeloma.org.

Scientists develop terminator virus

Researchers at Columbia University Medical Center continue to make strides in their work to develop the next generation of effective viral-based therapies for cancer. Two papers about promising research with genetically engineered viruses studied in mice, published September 19 in the journals Cancer Research and the Proceedings of the National Academy of Sciences (PNAS), bring us significantly closer to this objective and the start of clinical trials with these viral-based therapies in cancer patients.

Both papers were led by Paul B. Fisher, M.Ph., Ph.D., professor of clinical pathology and the Michael and Stella Chernow Urological Cancer Research Scientist at Columbia University College of Physicians and Surgeons.

In the Cancer Research paper, the researchers discuss the development of a “terminator” virus, which was administered to mice with pancreatic cancers at both primary and distant sites. As predicted, when the virus was injected directly into the primary tumor, the virus destroyed not only the primary tumor, but also distant tumors. While the infection caused by the virus was sufficient to kill the primary tumor, a second) – eliminated the weapon added to the virus – interferon-gamma elicited an anti-tumor immune response against the distant metastases.

In the PNAS paper, Dr. Fisher and the team describe the production of a virus conceptually similar to the “terminator” virus, which selectively replicates and kills breast cancer cells in mice. Human breast tumor xenografts were established on both sides of immune-deficient mice. Results found that treating the tumors on just one side of the animal with very few injections of this modified virus not only cured the injected tumors, but also resulted in the destruction of the tumors on the opposite side of the animal.

“We are extremely excited about these results and the prospect of one day using a form of the cancer terminator virus in human clinical trials,” said Dr. Fisher, the study’s senior author. “While the results of these trials need to be investigated further and replicated in future trials, we believe that viral-based therapies will someday soon be a standard part of the cancer armamentarium.”

The “terminator” viruses have the potential to become effective treatments for a wide range of tumors - such as ovarian, pancreatic, breast, brain, prostate, skin (melanoma) and colon cancer - because the virus is constructed to exploit a characteristic of all solid cancers. However, clinical trials are necessary before such treatments can be approved by the U.S. Food and Drug Administration and available for patients.

These publications are a continuation of research published in the Jan. 25, 2005 issue of PNAS, where the same research team, also led by Dr. Fisher, incorporated gene therapy into a specially designed non-replicating virus to overcome one of the major hurdles of gene therapy: its tendency to kill normal cells in the process of eradicating cancer cells. The virus eradicated prostate cancer cells in the lab and in animals, while leaving normal cells unscathed.

The present cancer “terminator” viruses represent the next generation of therapeutic viruses that permit replication uniquely in cancer cells with simultaneous production of immune modulating and toxic genes. These viruses effectively eliminate primary tumors and distant tumors (metastases) without harming normal cells or tissues.

Dr. Fisher’s cancer research team includes Columbia University Medical Center investigators: Drs. Zao-zhong Su (research scientist), Devanand Sarkar (associate research scientist), Nicolaq Vozhilla (pathology technician), Eun Sook Park (pathology technician) and Pankaj Gupta (associate research scientist). Two scientists from Virginia Commonwealth University in Richmond, Va. are also involved in the research: Mr. Aaron Randolph (graduate student) and Dr. Kristoffer Valerie (professor).

Phase I Clinical Trial for CHIR-12.12

Chiron Corporation and XOMA Ltd. today announced the initiation of a second clinical trial of CHIR-12.12, a novel, fully human, antagonist antibody that targets the CD40 antigen. The Phase I trial is for patients with multiple myeloma, a type of cancer that is associated with expression of the CD40 antigen on the cancer cell surface. Chiron and XOMA announced the initiation of a Phase I clinical trial of CHIR-12.12 in patients with chronic lymphocytic leukemia in April 2005.

"We're pleased to move CHIR-12.12 into clinical studies in a second B-cell oncology indication," said John C. Castello, XOMA's chairman, president and chief executive officer. "Our collaboration with Chiron enables both companies to advance promising antibodies more quickly than either could alone."

The single-agent, open-label Phase I study of CHIR-12.12 is designed to evaluate the safety, dose tolerability and pharmacokinetic profile of CHIR-12.12 in patients with multiple myeloma. Translational medicine will be used to monitor biomarkers and allow correlation of these markers with response to CHIR-12.12 therapy, guiding the dosing regimen and the selection of responsive patient populations. The study is expected to enroll up to 40 patients at four leading cancer centers in the United States.

About CHIR-12.12

CHIR-12.12 is a fully human, antagonist antibody that targets the CD40 antigen. As shown in vitro in cell lines, in vivo in animal models and ex vivo in patient cells, CHIR-12.12 binds to tumor cells that express CD40 and antagonizes (prevents) CD40 ligand-mediated growth and survival of malignant B cells. Based on preclinical data, CHIR-12.12 also induces antibody-dependent cellular cytotoxicity (ADCC), killing CD40 expressing tumor cells by immune effector cells. This dual mechanism of action makes CHIR-12.12 a drug candidate with potential for the treatment of B-cell malignancies.

Cancer causing substances

Have you ever wondered what causes cancer? There are varying opinions, but here is a link to the list published by the U.S. Government, Department of Health and Human Services.

http://ntp.niehs.nih.gov/index.cfm?objectid=72016262-BDB7-CEBA-FA60E922B18C2540

Here's the link directly to the list:

http://ntp.niehs.nih.gov/index.cfm?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932

Immune therapy discovery

In studies with mice, treatment with a new monoclonal antibody that targets immune system B cells has shown considerable promise for treating leukemias, autoimmune diseases and transplant rejection, according to immunologists at Duke University Medical Center.

B cells are the immune system's "arms factories," producing antibodies that target invading microbes for destruction. Abnormal B cell proliferation causes such leukemias as multiple myeloma and acute lymphoblastic leukemia, and such autoimmune diseases as rheumatoid arthritis and lupus.

The researchers, led by Professor and Chair of Immunology Thomas Tedder, Ph.D., reported their findings in the online Early Edition of the Proceedings of the National Academy of Sciences the week of Oct. 10, 2005. Other co-authors of the paper were Norhito Yazawa, Yasuhito Hamaguchi and Jonathan Poe in Tedder's laboratory. The research was sponsored by the National Institutes of Health.

Monoclonal antibodies (mAbs) are those created to target a specific protein. In their studies, the Duke researchers used mAbs targeting a protein called CD19 that is found on the surface of B cells. As their experimental animal models, they used mice that had been genetically altered to produce a human version of the CD19 protein on their B cells.

Their studies demonstrated that CD19 mAbs did tag B cells containing that protein, and that these B cells were then destroyed by the immune system.

When the researchers administered the CD19 mAbs to the mice, they found that it greatly depleted mature B cells, as well as precursor and immature B cells in the animals. The depletion of precursor and immature B cells is important because aberrant versions of such cells cause a number of leukemias and other malignancies where new therapies are needed, said Tedder.
And, they found that giving the mice CD19 mAbs, along with a mAb that targets another B cell protein, CD20, resulted in additive effects on B cell depletion. A CD20 mAb is now marketed as Rituximab.

Importantly, the researchers found that the CD19 mAb treatment dramatically depleted growth of malignant B cell tumors in the animals. In ten mice transplanted with malignant B cell lymphomas, the CD19 mAb treatment prevented the appearance of circulating and tissue tumor cells for up to seven weeks in all the animals. In contrast, all untreated mice died from their tumors by three weeks.

"We were actually quite shocked at how effectively CD19 mAb-treatments prevented malignant B cell expansion," said Tedder. "Treatment of such tumors in mouse models is extraordinarily difficult."

Finally, when the researchers measured the effects of CD19 mAb treatment on blood levels of antibodies produced by B cells, they found a significant reduction in circulating antibody levels as well as B cell mediated "humoral immune responses" in the animals, including reductions in autoantibodies of the type produced in autoimmune diseases and transplant rejection.
According to Tedder, the results of the CD19 mAb animal studies warrant rapid advance to clinical trials for treatment of B cell leukemias and other malignancies that derive from early B cell precursors and perhaps antibody-producing B cells.

The CD19 mAbs may show broader effectiveness than Rituximab, he said, because CD20 is expressed only by mature B cells, in contrast to CD19, which is expressed by both mature and immature B cells and by antibody-producing cells.

Tedder noted that in general such immunotherapies are likely to produce far fewer side effects than current chemotherapies -- which can produce secondary malignancies, sterility and growth retardation in children who take them for leukemias.

In particular, the researchers' finding that the treatment greatly depletes B cells in the peritoneum -- a major source of autoantibody-producing cells in mice -- could make it an effective treatment for autoimmune diseases such as lupus, said Tedder.

"In addition, this treatment could greatly aid transplant patients who require multiple organ transplants because they develop a humoral antibody response to their transplanted organs, or they already have preformed antibodies that prevent them from accepting some donor grafts." In contrast to the potentially benign nature of the CD19 mAb treatment for such patients, current therapy involves removing the spleen and giving such patients chemotherapeutic treatment and plasmapheresis to remove antibodies from the blood.

Tedder and his Duke colleagues are now developing plans for clinical trials at Duke of the CD19 mAbs in leukemias as well as autoimmune diseases. Also, a company that he founded, Cellective Therapeutics, Inc., will be further developing the therapy.

Eat more beans

A diet rich in beans, nuts and cereals could be a way to prevent cancer, believe UK researchers. Scientists at University College London have discovered that these everyday foods contain a potent anti-cancer compound.

This blocks a key enzyme involved in tumour growth, they told Cancer Research journal. The researchers say, in the future, it might be possible to mimic this compound in an anti-cancer drug.

Scientists have been exploring the enzyme phosphoinositide 3-kinase as a target for cancer treatment for some time but inhibitors have been difficult to develop because of problems with chemical stability and toxicity.

Dr Marco Falasca and colleagues have discovered that a natural compound, called inositol pentakisphosphate, which is found in most legumes as well as in wheat bran and nuts, blocks the activity of the enzyme.

When they tested its action in mice with ovarian and lung cancer they found it not only blocked tumour growth but also enhanced the effect of other cancer-killing drugs. In addition, it appeared to be non-toxic, unlike conventional chemotherapy agents.

Dr Falasca said: "Our study suggests the importance of a diet enriched in foods such as beans, nuts and cereals which could help prevent cancer.

"Our work will now focus on establishing whether the phosphate inhibitor can be developed into an anti-cancer agent for human therapy. "We believe that inositol pentakisphosphate is a promising anti-cancer tool and we hope to bring it to clinical testing soon."

He said researchers were also looking at whether people who eat more lentils, peas and beans are actually at lower risk of developing cancers

"What we do know already is that a diet that includes at least five portions of fruit and vegetables a day can help to reduce the risk of cancer."

Story from BBC NEWS

Melphalan/Prednisone in MM Patients ineligible for High-Dose Therapy

According to a recent article, the treatment combination consisting of the chemotherapy agent melphalan (Alkeran®) plus the steroid prednisone appears to be favorable to dexamethasone-based therapies among newly diagnosed patients with multiple myeloma who are not candidates for high-dose therapy.

The only potential curative treatment option for multiple myeloma involves high-dose therapy and a stem cell transplant. However, this procedure is often prohibitively dangerous to a large portion of patients with multiple myeloma, either due to other existing medical conditions or increased age. As a result, treatment combinations among patients not eligible for standard therapy are still being evaluated. Since patients with multiple myeloma survive a long time without being cured, quality of life is an important consideration when deciding upon optimal treatment strategies.

Researchers from France recently conducted a clinical trial to compare dexamethasone-based therapies to melphalan/predisone in the treatment of newly diagnosed patients with multiple myeloma. This study included 488 patients who were not eligible for high-dose therapy. (Dexamethasone is a steroid that may be used alone or in combination with other agents for the treatment of multiple myeloma.)

Patients received one of the following treatment combinations: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Overall survival was consistent among the four treatment groups:

• Anticancer responses were higher among patients treated with melphalan-dexamethasone.
• Progression-free survival was higher among patients who had melphalan in their treatment regimen.
• There was no difference in overall survival between the four treatment groups.
• Quality of life and side effects were significantly worse in patients with dexamethasone in their treatment regimen.

The researchers concluded that melphalan-prednisone appears to be the treatment of choice when considering dexamethasone-based therapy for newly diagnosed multiple myeloma patients. Dexamethasone does not improve survival. It does, however, increase side effects compared with melphalan-prednisone. Different agents and treatment combinations may be superior to melphalan-prednisone for patients with multiple myeloma; therefore, it is important that patients discuss individual risks and benefits of all treatment choices with their physician.

Reference: Facon T, Mary J, Pegourie B, et al. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2005 Sep 20; [Epub ahead of print]

Relapse after auto - Thal and Dex are effective

Thalidomide plus dexamethasone is an effective salvage regimen for myeloma patients relapsing after autologous transplant. Eur J Haematol 2005: 75: 391-395. (c) Blackwell Munksgaard 2005.

Objectives: High-dose therapy followed by autologous transplant (AT) is the effective induction treatment for newly diagnosed multiple myeloma (MM) patients. The best salvage therapy has not been defined; treatment options include thalidomide plus dexamethasone (TD), AT and conventional chemotherapy (CC). The aim of the study was to define the best treatment option for patients relapsing after AT.

Patients and Methods: We compared the outcome of 90 MM patients treated at diagnosis with AT and then salvaged with TD (43 patients), AT (28 patients) or CC (19 patients). The major prognostic factors, the median times between diagnosis and start of salvage treatment and the progression-free survival (PFS) from diagnosis were similar among the three groups. Results: The response rate was higher after salvage AT and after TD, and lower after CC (P<0.001). TD significantly prolonged PFS from first relapse (P<0.0001). Median PFS was 20.3 months after TD, 9 months after AT, and 4.5 months after CC. Overall survival (OS) from first relapse was significantly improved by TD (median OS 55.5 months) but not by AT (15 months) or CC (27.5 months) (P=0.008). Multivariate analysis indicated that TD and age were the only independent risk factors associated with improved outcome. Conclusion: TD improved PFS and OS in myeloma patients relapsing after AT.

Palumbo A, Falco P, Ambrosini MT, Petrucci MT, Musto P, Caravita T, Pregno P, Bertola A, Cavallo F, Ciccone G, Boccadoro M.

Divisione di Ematologia dell'Universita di Torino, Torino, Italy

PMID: 16191088 [PubMed - in process]

Cancer diet

Here is a very interesting web site with some pretty wild menu items.

http://www.cancerrd.com

The site is created by Diana Dyer a nutritionist and cancer survivor.

Celgene Review Extended by the FDA

The Food and Drug Administration has decided to extend its review of the cancer-fighting drug Revlimid by three months, according to Celgene Corporation.

The FDA was expected to approve Revlimid this week for the treatment of myelodysplastic syndromes.

The review’s extension is a result of the FDA requiring more time to review additional information on Celgene’s RevAssist risk-management program. According to the company, the RevAssist program includes physician education, as well as interim pregnancy testing before and during treatment.

Revlimid is a derivative of thalidomide, a drug associated with birth defects, and the delay in approval for Revlimid is designed to satisfy the FDA that a fetus would not be exposed to the drug.

Celgene had already submitted animal studies that showed Revlimid’s structure and biology were different from thalidomide and did not cause birth defects in rats and rabbits.

Celgene has been marketing thalidomide under the product name Thalomid since 1998 for the treatment of leprosy. However, many physicians use it on an “off-label” basis to treat multiple myeloma, although it is not officially approved.

Thalomid has rigorous restrictions on its use, including frequent pregnancy testing of female patients, to protect fetuses from exposure. Celgene said that they are discussing a similar program for Revlimid with the FDA.

Atiprimod Active in Mouse Model of Multiple Myeloma

Callisto Pharmaceuticals, Inc. (AMEX: KAL), today announced that Atiprimod inhibits growth of tumors in a cutting-edge animal model of human multiple myeloma. Dana-Farber researchers developed the unique animal model to improve their ability to study the drug's effectiveness as a potential new therapy.

The article which appeared in the July issue of the American Society of Hematology's journal Blood, Volume 106, Number 2, pp.713-716 (2005), and is entitled, "A clinically relevant SCID-hu in vivo model of human multiple myeloma," was authored by a team of scientists at Dana-Farber Cancer Institute and Callisto Pharmaceuticals, Inc.

"The Dana-Farber research team is well known for their pioneering research and clinical activities in the field of multiple myeloma," said Dr. Gary S. Jacob, Chief Executive Officer of Callisto Pharmaceuticals. "Their present paper describes an elegant mouse model of the human disease, and demonstrates that Atiprimod inhibits growth of MM tumors in this model. What's more, this work demonstrates that Atiprimod can target human MM cells in the human bone marrow microenvironment."

Multiple myeloma can be treated with drug therapies. However, a significant number of multiple myeloma patients stop responding to existing drugs; Atiprimod is being developed as a novel alternative treatment option for these so-called relapsed patients.

The manuscript described a novel in vivo MM model developed by engrafting a human MM cell line into severe combined immunodeficiency (SCID) mice previously given implants of a human fetal bone chip. Researchers from Dana-Farber monitored growth of these IL-6 dependent human MM cells by measuring the level of soluble human IL-6 receptor in mouse serum and by fluorescence imaging of host animals.

Atiprimod is currently being evaluated in a Phase I/IIa clinical trial in relapsed or refractory multiple myeloma patients at four clinical sites in the United States -- the Dana-Farber Cancer Institute (Boston, MA), the M.D. Anderson Cancer Center (Houston, TX), the St. Vincent's Comprehensive Cancer Center (New York, NY) and the Roswell Park Cancer Institute (Buffalo, NY).

About Callisto Pharmaceuticals, Inc.

Callisto is a biopharmaceutical company focused on the development of drugs to treat cancer and osteolytic bone disease. Callisto has two lead drugs in clinical development, Annamycin to treat relapsed leukemia, and Atiprimod to treat relapsed multiple myeloma. Callisto's second drug, Atiprimod, is in a Phase I/IIa clinical trial in relapsed multiple myeloma patients, and is a small-molecule, orally available drug with antiproliferative and antiangiogenic activity. Callisto has exclusive worldwide licenses from AnorMED Inc. and M.D. Anderson Cancer Center to develop, manufacture, use and sell Atiprimod and Annamycin, respectively. For investor-specific information about Callisto, including recent news and stock price data, please visit http://www.trilogy-capital.com/tcp/callisto/