Month: August 2008

Shingles

No, I don’t have shingles again, but I noticed that it’s one of the biggest searches that brings people here. To skip to posts that mention shingles, click here.

I’ve had shingles three times. The very first time, I had no clue what it was. Each time thereafter I did.  There have been clear signs that I was going to have a case. In advance of the rash, I felt generally unwell. My most recent outbreak was on the left side of my head, and was preceded by an earache, headache and sore throat just on that side.  Each time, the skin in the area where the rash would soon appear was extremely sensitive and sometimes felt almost as a burning sensation, but very mild.

Once the rash appears, there can be itching and sharp stinging. Sometimes the stinging is enough to make me say ouch! Even after the rash clears up, there’s still some stinging and itching.  It eventually wears off, but I still have itching on my head where the rash used to be. Certain spots are still extremely sensitive at times.

I’ve been told that it’s necessary to start an anti-viral such as Famvir as soon as possible to lessen the likelihood of post herpetic neuralgia, but that it will not be effective if started too late. If the rash has been present for more than 3 days, it may not do any good to be on an anti-viral.  Some myeloma patients are on an anti-viral persistently in an effort to prevent the ocurrance of shingles.  I’ve not done that, because I don’t like the side effects of the drug Famvir, which gives me headaches.

Shingles is caused by the varicella zoster virus, which is the same thing that causes chicken pox.  If you have never had chicken pox, you won’t get shingles. You can get chicken pox from someone who has shingles though!

More about shingles

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

Treatment with anti-anemia drugs may not be safe for multiple myeloma patients

How will this affect the treatment of anemia? Will it mean more transfusions and less ESAs? I’ve only ever had a few shots of Procrit, and have never had red blood cells (just platelets). What I’m afraid will happen is that people will be afraid of ESAs. If you think about it, the statement at the end of the summary makes a lot of sense. Were the patients in the group who were given the ESAs just more sick, with a poorer prognosis?

Public release date: 4-Aug-2008

Contact: Sean Wagner
swagner@wiley.com
781-388-8550
Wiley-Blackwell
Treatment with anti-anemia drugs may not be safe for multiple myeloma patients

Thessaloniki, Greece – August 4, 2008 – A recent study published in American Journal of Hematology demonstrated that Erythropoiesis-stimulating agents (ESAs), a widely used drug to treat anemia, may have a negative impact on the survival of myeloma patients. In the study, 323 multiple myeloma patients were evaluated over a 20 year period in Greece from 1988 to 2007. The investigators reviewed their medical records and observed an association between ESA exposure and a reduction in progression-free and overall survival.

The study demonstrated that ESA administration may influence the course of the disease, in that people who received ESA may progress earlier than those who did not receive ESA. The median survival rate was 31 months for patients who were administered ESAs, compared to 67 months in those who were not exposed to ESAs. The median progression-free survival for patients in the ESA group was 14 months, and 30 months for those without ESA exposure.

For the past 15 years, erythropoiesis-stimulating agents have been used in the management of cancer-related anemia, but researcher Eirini Katodritou stresses the possible harmful effects ESAs may have on cancer patients. “Physicians should use ESAs with caution, based on the International Guidelines for ESA administration in cancer and on certain prognostic indicators to guide their use. Physicians need to identify the appropriate group of cancer patients who will benefit from ESA administration, while avoiding possible detrimental effects,” said Katodritou.

The question of whether ESAs are harmful in patients with myeloma is a pressing clinical issue with at least eight prospective controlled clinical trials in the last five years reporting poorer outcomes with ESA use in patients with cancer, according to Dr. David P. Steensma of the Mayo Clinic. However, only two of those studies included some patients with myeloma. Dr. Steensma pointed out that the patients in the retrospective Greek study were imbalanced for many of the known prognostic markers in myeloma, indicating that sicker patients were given ESAs preferentially and that this group would have been predicted to do more poorly anyway. Although this imbalance might explain the results, Dr. Steensma discussed the importance of additional prospective studies of ESA safety in myeloma and other forms of cancer.

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