Category: Cancer

Classic myeloma? A bit of an explanation.

On the mailing list we had a discussion about bone disease in MM.  Here’s what Nancy said about it. I hadn’t realized before that IgA patients are less prone to bone disease.  One of my doctors did tell me we’re more likely to have kidney involvement though.

Some people never have bone disease…that’s just the way their myeloma is; just as some people never have kidney problems. The names given to the variations of myeloma are not different. Patients with IgA myeloma are less likely to have bone disease than those with IgG myeloma…and those with IgG myeloma are less like than those with IgA myeloma (or Bence Jones myeloma) to have kidney problems.

Perhaps by “classic myeloma” they are referring to myeloma that is in the bone marrow…as opposed to extramedullary myeloma which is outside the bone marrow….rather than affecting the bones. However, about 80% of patients do have bone involvement, so it is the most common symptom of myeloma.

For more information about multiple myeloma, visit the IMF web site:
http://myeloma.org

Fred Baron dies soon after receiving approval to use Tysabri

Dallas attorney, Fred Baron, lost his battle with multiple myeloma on Thursday. He was 61 years old. Mr. Baron made the news when he tried to get the Biogen drug Tsyabri to treat the myeloma that was taking his life. There aren’t any reports about whether or not Mr. Baron actually was treated with the drug.

I had never heard of Mr. Baron before a few weeks ago even though he was a supporter of and fundraiser for John Edwards. Edwards was a democratic candidate for president this year and vice president in 2004. He was a North Carolina senator whose affair with a woman who produced videos for his campaign probably ruined his future in politics. According to the Dallas News, Mr. Baron was the friend who got Mr. Edwards’s mistress out of Dodge when it was feared knowledge of the affair would go public.

Elizabeth Edwards, wife of John Edwards, has breast cancer with bone metastasis. It was discovered during his presidential campaign after she fractured a rib while moving some furniture, according to the News and Observer.

Fred Baron, Myeloma and Tysabri

Have you read about the furor over Fred Baron’s quest to get Tysabri to attempt to treat his myeloma?

According to his son’s blog, they believe it could help prolong his life. Andrew Baron says that Biogen, the maker of Tysabri (a drug used to treat MS), will not allow him to have the drug.  It is, however, being tested on MM patients in a phase I trial.

I still have to do some reading on this drug. The side effects are potentially serious, but, when you have only weeks left to live, I don’t suppose that matters.

Andrew’s blog:  http://dembot.com/post/54498664/open-letter-to-james-c-mullen-ceo-of-biogen
http://www.pharmalot.com/2008/10/biogen-tysabri-a-dying-democratic-fundraiser/

Co-pay assistance for patients with Multiple Myeloma

Subject: Co-pay assistance for patients with Multiple Myeloma

Myeloma Treatment

Message: Beth,

I just wanted to shoot you a quick message to let you know about our
organization. Patient Access Network Foundation provides co-pay
assistance for medications to insured patients who cannot afford the
co-pays for their treatment. We currently have 20 disease funds
including Multiple Myeloma.

Patients are eligible for assistance as long as they have insurance
that covers part of the cost of the medication, their income is below
400% of the federal poverty level, and they are a US resident.

Patients can apply by visiting our website at
www.patientaccessnetwork.org or by calling to speak with one of our
case managers at 1.866.316.7261.

If you could pass this information on to other patients you know, or
post a link in your blog, we would really appreciate it! We’re
trying to help out every patient we can, and every little bit helps!

Thanks,

Ashley Hutton
Patient Access Network Foundation

Untapped Potential Of Antidepressants For Cancer

ScienceDaily (Sep. 13, 2008) — A comprehensive review of current scientific literature, published in the peer-reviewed journal ecancer, has suggested that antidepressants can help the human body fight cancer by boosting its own immune response, amongst other mechanisms.

Not only this but they can help with side effects from chemotherapy such as aiding sleep, stimulating appetite, combating pain and avoiding depression.

Antidepressants work by affecting levels of chemicals known as prostaglandins. These are ephemeral, infinitesimal signallers self-regulating every cell in the body, including those serving mood and immunity. When first discovered they were perceived as a master switch, but are now believed to regulate every component of cellular microanatomy and physiology, including those of the organelles, cytoskeleton, proteins, enzymes, nucleic acids and mitochondria.

Prostaglandins are responsible, paradoxically, for both cell function and dysfunction. Excessive prostaglandin synthesis depresses immune function and may induce cancer.

An ideal anticancer agent would inhibit prostaglandins in such a manner as to shut down the pathogenesis of cancer. The article indicates that antidepressants have such properties.

Report author, Dr Julian Lieb of Vermont, USA, concludes that antidepressants have the potential to arrest, prevent, reverse and palliate cancer. He also points out that short of that they have many other uses in cancer care.

Antidepressants can reduce the severity and frequency of hot flushes in patients treated with chemotherapy, and venlafaxine (Effexor) remit acute neurosensory symptoms secondary to oxaliplatin chemotherapy. The monoamine oxidase inhibitors deprenyl and clorgyline protect nonmalignant cells from ionizing radiation and chemotherapy toxicity, and such antidepressants as nefadazone are capable of reversing chemotherapy-induced vomiting.

The report notes that as the response to antidepressants is highly specific, many patients require multiple trials before responding. It found that some subjects are non-responsive to all antidepressants, and some may relapse due to getting used to the drug. However, adjusting prostaglandins can induce both pro and anti-cancer actions. The constant presence of this paradox means that antidepressants may be capable of initiating or accelerating cancer and thus maintaining close clinical observation and limiting the duration of drug trials is essential.

The review also points out that epidemiological studies have failed to confirm the suspicion that antidepressants may induce breast cancer. However, breast cancer has been reported in three men taking selective serotonin reuptake inhibitors.

Dr Lieb added: “Wherever prostaglandin-synthesizing enzymes convert arachidonic acid to prostaglandins there are possible sites of action of antidepressants. By maintaining these enzymes within physiological limits, antidepressants shut down the mechanisms of carcinogenesis. Considerable evidence now shows that antidepressants are cytotoxic, cytostatic, convert multidrug resistant cells to sensitive, and protect nonmalignant cells from ionizing radiation and chemotherapy.

Antidepressants have potent pain relieving properties alone, or through enhancing narcotics, and they enhance sleep, appetite and occasionally energy. Their immuno-stimulating and antimicrobial properties may help with infection secondary to chemotherapy or radiation. Alleviation of anxiety, depression, fear of death, recrimination and remorse by antidepressants can be very beneficial, though care must be taken to monitor for negative effects such as intensification of depression or pain. Overall, the positive effects of antidepressants in cancer therapeutics far outweigh the negatives.”

ecancermedicalscience (2008, September 13). Untapped Potential Of Antidepressants For Cancer. ScienceDaily. Retrieved September 14, 2008, from http://www.sciencedaily.com­ /releases/2008/09/080911142620.htm#

Labs at Duke

A couple of days ago I had blood drawn at Duke in Durham, NC.  I should know in a few more days what the results are. They’re a little on the slow side where getting lab reports out are concerned. I’m not sure why it has to be that way.  I haven’t had any tests since June, so I’m a bit anxious about it.

I signed up for a course to learn how to shoot and edit video! I’ll let you know how it is and will be sure to share some of my work. Stay tuned.

Autologous Stem Cell Transplantation in Patients of 70 Years and Older With Multiple Myeloma: Results From a Matched Pair Analysis

Thanks to Carol for finding this new study.

Autologous Stem Cell Transplantation in Patients of 70 Years and Older With Multiple Myeloma: Results From a Matched Pair Analysis
Am J Hematol. 2008 Aug 1;83(8):614-617, SK Kumar, D Dingli, MQ Lacy, A Dispenzieri, SR Hayman, FK Buadi, SV Rajkumar, SV Rajkumar, MA Gertz

Multiple myeloma (MM) accounts for 1% of all malignancies and approximately 10% of all hematologic malignancies. In the United States, an estimated 19,900 new cases of MM were diagnosed in 2007, and 10,790 patients were expected to die of this disease. Patients with MM have a median age of onset in the seventh decade of life and 3- to 4-year median survival when treated with conventional chemotherapy. Newer combination chemotherapeutic agents have not improved the survival outcome achieved with melphalan and prednisone, which have been used for >30 years. High-dose chemotherapy (HDT) followed by autologous stem cell rescue has resulted in improved survival and quality of life compared with conventional strategies. For patients with MM who qualify for HDT, this approach has become the standard of care.

Many of the larger clinical trials in which HDT was examined only included patients <65 years of age. However, a significant proportion of MM patients are >65 years. Therefore, it remains unclear whether the benefits observed in younger patients would extend to an older population. This case-controlled study evaluated the outcome of HDT in patients with MM who were >70 years.

A total of 93 patients were included in the study. All had undergone HDT and stem cell transplantation for MM. The study group included 33 patients >70 years and a matched control group of 60 patients <65 years. The baseline characteristics of the 2 groups were comparable, with the only difference being the type of conditioning regimen used. The dose of the melphalan conditioning regimen was reduced in 30% of patients in the elderly group as opposed to only 5% of patients in the younger group.

A trend toward a longer hospital stay after transplant was noted for the elderly vs the younger group (8 vs 3 days). By day 15, engraftment occurred in 94% of the elderly group vs 78% of the control group (P = .08). The adverse reactions most often seen were nausea, vomiting, hypertension, and tachycardia; no significant differences between the groups were evident. The overall response rates were 97% and 98% for the elderly and control groups, respectively. A complete response was achieved by 42% of the elderly group vs 28% of the control group. The patients were observed for a median of 27.2 and 38.3 months in the elderly and younger groups, respectively. The post-transplant median overall survival duration was 53.3 months in the younger patient group; the elderly patient group did not reach its median overall survival during follow-up. In the subset of patients receiving reduced-dose melphalan, there was no difference in time to progression or overall survival compared with
patients receiving standard-dose melphalan.

Previous trials have clearly shown a benefit of HDT in patients <65 years of age. However, investigators have not studied the benefit of HDT for patients 70 years of age and older. This study showed that patients older than 70 years have outcomes similar to those in younger patients (<65 years of age). The treatment-related mortality rate and the kinetics of engraftment were similar between the 2 study groups. Despite a greater proportion of the older group of patients receiving a reduced dose of melphalan, no significant differences were evident with respect to response rate or time to progression between the 2 groups. This retrospective study showed a benefit for patients >70 years who underwent HDT for MM. Age alone should not be the sole factor used when evaluating whether a patient is eligible to undergo HDT. Dose reduction should be considered for the older population of patients when appropriate.

SYNTHETIC MOLECULES COULD ADD SPICE TO FIGHT AGAINST CANCER

Thanks to Sandy for telling me about this.

COLUMBUS, Ohio – Seeking to improve on nature, scientists used a spice-based compound as a starting point and developed synthetic molecules that, in lab settings, are able to kill cancer cells and stop the cells from spreading.

The researchers are combining organic chemistry, computer-aided design and molecular biology techniques in developing and testing pharmaceutical compounds that can fight breast and prostate cancer cells. The synthetic molecules are derived from curcumin, a naturally occurring compound found in the spice turmeric.

Centuries of anecdotal evidence and recent scientific research suggest curcumin has multiple disease-fighting features, including anti-tumor properties. However, when eaten, curcumin is not absorbed well by the body. Instead, most ingested curcumin in food or supplement form remains in the gastrointestinal system and is eliminated before it is able to enter the bloodstream or tissues.

“Newer evidence describes how curcumin interacts with certain proteins to generate anti-cancer activity inside the body. We’re focusing on the pathways that are most involved in cancer and trying to optimize for those properties,” said James Fuchs, assistant professor of medicinal chemistry and pharmacognosy at Ohio State University and principal investigator on the project.

Fuchs presented the research today (8/17) at the American Chemical Society meeting in Philadelphia. He described a selection of the 40 compounds developed to date, emphasizing the synthetic molecules that appear to have the most potential to serve as the basis for anti-cancer drug development.

Fuchs and colleagues are continuing to refine compounds that are best structured to interact with a few overactive proteins that are associated with cell activity in breast and prostate cancers. Blocking these molecular targets can initiate cell death or stop cell migration in the cancers.

A major component of their strategy is called structure-based, computer-aided design, a relatively new technology in the drug discovery field. Before ever working with an actual compound, the scientists can make manipulations to computer-designed molecules and observe simulated interactions between molecules and proteins to predict which structural changes will make the most sense to pursue.

“Very small changes that may seem insignificant can have dramatic effects on these toxicity properties,” Fuchs said. “But most of the compounds we’ve made have been more potent than curcumin against the cancer cells.”

“Most of the interaction between our compound and the overactive protein comes from what are called hot spots on the protein’s surface,” said Chenglong Li, assistant professor of medicinal chemistry and pharmacognosy at Ohio State and an expert in computational chemistry. “For each spot, we can design small chemical fragments and link them together to make a molecule. This is what computer-aided design and modeling can do.”

Some of the most effective compounds have been tested for their effectiveness against human cancer cell lines – as well as whether they might be toxic to healthy cells. So far, the molecule favored by the researchers has a nearly 100-fold difference in toxicity to cancer cells vs. healthy cells, meaning it takes 100 times more of the compound to kill a healthy cell than it does to kill a cancer cell.

“Very small changes that may seem insignificant can have dramatic effects on these toxicity properties,” Fuchs said. “But most of the compounds we’ve made have been more potent than curcumin against the cancer cells.”

The computer-based predictions have suggested that the most effective compound developed to date can interact with proteins believed to be active in about 50 percent of all breast and prostate cancers.

“To be able to develop a drug that in the future could have potential to treat 50 percent of these cancers would be a major contribution,” said Jiayuh Lin, an investigator in Ohio State’s Comprehensive Cancer Center and an associate professor of pediatrics. Lin tests the experimental compounds in different types of breast and prostate cancer cell lines. He said some of the compounds also show potential to kill pancreatic cancer cells and inhibit cancer cell migration.

The computer-aided design also offers hints at the compounds’ suitability as the basis for a drug, such as whether the molecules will remain stable during metabolism and whether they will maintain a structure that the body can absorb into the bloodstream and tissues. The team is planning to continue refining the compounds before advancing to animal studies to test their effectiveness. The scientists hope to develop a chemotherapeutic agent available in pill form.

Additional members of the research group, dubbed the OSU Molecular Target Team, are Pui-Kai Li, chair and associate professor, and graduate students Jonathan Etter, Dalia Abdelhamid, Nicholas Regan, Deepak Bhasin, Bulbul Pandit and Katryna Cisek, all of Ohio State’s Division of Medicinal Chemistry and Pharmacognosy; and Ling Cen, Li Lin and Brian Hutzen of the Center for Childhood Cancer in the Research Institute at Nationwide Children’s Hospital in Columbus.

This work is supported by the Department of Defense Prostate Cancer Research Program, the James S. McDonnell Foundation, the National Foundation for Cancer Research, Ohio State’s Comprehensive Cancer Center and Ohio State’s College of Pharmacy.

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Contact: James Fuchs, (614) 247-7377; Fuchs.42@osu.edu or Chenglong Li, (614) 247-8786; cli@pharmacy.ohio-state.edu
http://researchnews.osu.edu/archive/curcumin.htm

Written by Emily Caldwell, (614) 292-8310; Caldwell.151@osu.edu