Chemotalk Newsletter, Vol. 13: June 1, 2009
Hi, Everybody... Summer at last!
I've been lagging about writing this month's newsletter because I've got mixed feelings about self-promotion, no matter how worthy the cause. But I've got to do it, so here goes:
My book, "I'm Hot!...and I'm Bald!": CHEMOTHERAPY FOR WINNERS, is now available on Amazon.com and Kindle, as well as on the website "www.chemotalk.com. If anyone wants said book and decides to buy it online, I would very much appreciate if that person would write a review. Amazon requires a purchase before anyone can review any book - and that's fair. How else would someone know if the book is worth the bucks, unless they buy it and (presumably) read it? So it's there, if anyone you know is using chemo, or caring for someone going through treatment. And as you know by now, it's not just for cancer. Anyone with MS, RA, or who has had an organ transplant, is also using chemotherapy as their standard of care.
Now, to this month's chemo, or chemo-related news:
DELIVERING CHEMO DIRECTLY INTO BRAIN TUMORS SHOWS PROMISE
Using a catheter to deliver chemotherapy drugs directly into a deadly type of brain tumor is showing promise in early clinical trials ... good news, indeed, since malignant gliomas are difficult to treat using standard chemotherapy and radiation treatments.\
Only about 3% of patients diagnosed with a malignant glioma survive five years or more, according to background information in the study. With the new method, researchers inserted catheters carrying the chemotherapy drug Topotecan (Hycamtin) directly into the tumors of 16 patients with recurrent malignant gliomas. The patients who received the Topotecan had a median survival of 59 weeks, although a few patients lived much longer. The median time to tumor progression was 20 weeks, and 77% of patients survived for at least six months.
"Those numbers are better than any treatment for recurrent gliomas we have now," said study author Dr. Jeffrey Bruce, co-director of the Brain Tumor Center at Columbia University Medical Center in New York City.
Malignant gliomas are typically resistant to treatment for several reasons, explained Dr. Paul Fisher, an associate professor of neurology and pediatrics at Stanford Medical Center and the Beirne Family Director of Neuro-Oncology. Chemotherapy is typically given orally or intravenously. In brain tumors, chemotherapy is not very effective, because drugs are not able to penetrate the blood-brain barrier, which prevents most drugs in the bloodstream from entering the brain.
Malignant gliomas also send out tentacles, making the tumors very difficult to completely remove surgically. Even when there's no tumor visible, microscopic glioma cells usually remain that eventually regrow, Fisher said.
Sen. Edward Kennedy is currently battling a malignant glioma, and it's rumored that he'll be returning to work after the Memorial Day weekend.
In the lab, Topotecan had been shown to be effective in killing malignant glioma cells, but delivering enough of it through the bloodstream to attack brain tumors would cause too many toxic side effects. So for four days, using a procedure called convection-enhanced delivery, Topotecan was pumped into tumors in 16 patients through two catheters. The pumping was done very slowly, at a rate of several drops an hour, Bruce said. Side effects included upper extremity weakness and left parietal syndrome, neurological issues caused by damage to the brain.
The patients had two types of tumors: 10 had a glioblastoma multiforme (GBM), an invasive and fast-growing tumor, while six had anaplastic glioma.
The next step will be multi-center Phase 2 clinical trial, which will begin in the next two to three months, Bruce said.
A second study also explored an alternative method of delivering chemotherapy drugs to malignant gliomas, this time using nanoparticles.
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ANOTHER DIRECT DELIVERY ADVANCE, THIS ONE TARGETING PANCREATIC CANCER
Researchers are reporting that they've discovered a way to boost chemotherapy and slightly extend the lives of mice with PANCREATIC CANCER, potentially paving the way for more effective treatments in people. (That's usually how it goes, folks...mice, first. Then us.)
There's no guarantee that the strategy would work in humans. Still, scientists are "cautiously optimistic," said Dr. David Tuveson, lead author of a study released online May 21 in Science and a researcher at the Cambridge Research Institute in England.
Pancreatic tumors are among the most difficult types of cancer to treat. Roughly 5 percent of people diagnosed with the more common form of the disease are expected to survive five years from diagnosis, according to the American Cancer Society.
"It usually gets diagnosed when it is already very advanced because the symptoms don't usually begin until the cancer is advanced," said Dr. Allyson J. Ocean, assistant professor of medicine at the Jay Monahan Center for Gastrointestinal Health at New York-Presbyterian Hospital/Weill Cornell Medical College in New York City. Pancreatic cancer is resistant to chemotherapy and radiation, she added, and tumors are often aggressive and likely to spread.
Doctors think the disease is especially difficult to treat with chemotherapy because the tumors don't have many blood vessels to carry drugs to where they need to be to kill cancer cells.
In the study, researchers genetically engineered mice to develop a form of pancreatic cancer. The scientists then gave them a chemotherapy drug called gemcitabine (Gemzar) and another compound they hoped would boost blood flow in the tumors. The survival time of the mice, on average, doubled from 11 to 25 days when they were treated with the chemotherapy drug and the compound, which is known only by a code. That may not seem like much, Tuveson said, but in people, "a doubling of overall survival from six to 12 months would be meaningful."
Some previous pancreatic treatments have worked well in mice but failed in humans. But the researchers behind the new study may have discovered a "trick" to a more effective treatment. In the big picture, the treatment might extend life span by just a few months. But the strategy could help make tumors more vulnerable to other types of chemotherapy drugs. "It's possible that other chemotherapy drugs that failed before could become effective."
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MORE GOOD NEWS: STEM CELL STUDY OFFERS HOPE FOR TARGETING TUMORS
Genetically engineered adult stem cells, armed with a CANCER-killing protein, have proven successful at targeting several types of tumors while sparing healthy cells, new research has found.
Stem cells carrying TNF-related apoptosis-inducing ligand (TRAIL) destroyed lung, squamous, breast and cervical cancer cells in laboratory cultures, according to British researchers. When tried on mice, the specialized cells shrunk subcutaneous breast tumors by about 80%, and when injected intravenously, they helped destroy about 38% of metastasized lung tumors in rodents.
The study results combined findings from two previous areas of research: one that found that mesenchymal stem cells (MSCs), which come from bone marrow, can work as messengers to tumors cells, and another that found TRAIL effective at killing cancer while sparing healthy cells.
"This is the first study to demonstrate a significant reduction in tumor burden with inducible TRAIL-expressing MSCs in a well-controlled and specifically directed therapy," the authors, Dr. Michael Loebinger and Dr. Sam M. Janes of the Centre for Respiratory Research at the University College London, noted in a news release from the American Thoracic Society.
The authors said it could be at least two years before these specialized stem cells are tried on people. Loebinger noted, for example, that while the MSCs seem to be naturally drawn to the cancer cells, the reasons for this are not fully understood.
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The following study is a little technical, but you'll get the drift, and the information is important.
PREDICTING RHEUMATOID ARTHRITIS:
Validation of a Prediction Rule for Disease Outcome in Patients With Recent-Onset Undifferentiated Arthritis: Moving Toward Individualized Treatment Decision Making
Patients with early undifferentiated inflammatory arthritis (UA) from 3 cohorts (United Kingdom, Germany, and The Netherlands) were followed over 1 year or more to determine whether a prediction rule for rheumatoid arthritis (RA) would accurately identify patients who progressed to RA, on the basis of the American College of Rheumatology (ACR) 1987 revised criteria. Depending on the cohort, UA was defined as ≥ 1 or ≥ 2 swollen joints; subjects did not meet other diagnostic criteria for forms of inflammatory arthritis.
The duration of UA at inclusion varied among cohorts: United Kingdom ≤ 3 months, Germany 1-12 months, and Dutch < 2 years. At initial assessment, researchers obtained data with regard to age, sex, morning stiffness, number and distribution of tender/swollen joints, C-reactive protein (CRP) levels, and rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) antibodies. They then scored these factors as part of a "prediction rule," and evaluated the relationship between the prediction rule score (0-14) and fulfillment of RA criteria at ≥ 1 year of follow-up.
In combined cohort analysis, a prediction score of ≥ 8 resulted in a positive predictive value of 97% for fulfillment of RA criteria at ≥ 1 year of follow-up. RF, anti-CCP, and CRP elevations were the strongest predictors for a future diagnosis of RA. A prediction score of ≤ 6 resulted in 83% negative predictive value for fulfillment of RA criteria at ≥ 1 year. The study authors pointed out that it was difficult to predict outcomes in patients with prediction rule scores between 6 and 8, and that, because a significant proportion of patients were treated with disease-modifying antirheumatic drugs (DMARDs) before the fulfillment of ACR RA criteria (22% in the UK cohort; 25% in the German cohort), this prediction rule may underestimate risk for RA.
Clinical trial data have shown that early identification and treatment of patients with RA as defined by ACR criteria lead to improved outcomes. However, patients with inflammatory arthritis may not initially present with symptoms/signs meeting the full ACR RA criteria. Moreover, a significant proportion of patients presenting with inflammatory arthritis may not have persistent disease. Thus, it can be difficult to know which patients to treat aggressively when they initially present with symptoms of inflammatory arthritis.
The study authors presented interesting data with regard to the ability to predict which patients with early UA might progress to RA. However, the heterogeneity of the cohorts included in this study, including the high percentage of patients treated with DMARDs, makes these findings difficult to apply in clinical practice. On the basis of this study, how should clinicians define early UA: 1 or more swollen joints, or 2 or more? Less than 3 months of symptoms, or less than 2 years?
The positive predictive value and negative predictive value for the cohort-specific data were relatively similar, which may help us apply this prediction rule to patients with various clinical presentations, but larger studies with more homogeneous inclusion criteria would be helpful. Also, this study assumes that fulfillment of the ACR RA criteria is a marker for more destructive disease, but is it really? Not all RA behaves the same way; some RA is erosive and destructive and some is not. It would be beneficial to know how well this prediction rule identifies early subjects who will progress to more severe disease (ie, erosions or disability) rather than just those who will fulfill the ACR RA criteria.
Finally, we need to know which treatments are best for preventing progression to more destructive disease. These Dutch authors previously presented data from the PROMPT (Probable Rheumatoid Arthritis: Methotrexate versus Placebo Treatment) trial, which suggested that treatment with methotrexate in early UA can delay progression to overt RA. The PROMPT results are interesting, but we need more data before knowing which patients with early UA would need which drug -- hydroxychloroquine vs methotrexate vs combination therapy, or perhaps a biologic agent.
Regardless of these issues, the study authors have made a valuable contribution to helping us understand which patients with early UA (undifferentiated arthritis) may be at risk for more persistent disease in the future. We should watch for future contributions from this group with regard to the difficult issue of evaluation and treatment of early UA.
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More news about Rheumatoid Arthritis:
FDA OKs SIMPONI FOR RHEUMATOID ARTHRITIS
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I chose this story because a lot of cancer patients are taking the oral chemo drug Xeloda. I took it myself, for 6 months. I didn't travel during that time, so I didn't notice this side effect, even if it was there. But it's so weird it just deserves notice:
CANCER DRUG ERASES MAN'S FINGERPRINTS
Eng-Huat Tan, MD, a senior consultant in the medical oncology department at Singapore's National Cancer Center, says his patient, identified as "Mr. S," had been taking the drug Xeloda since July 2005 to prevent recurrence of advanced cancer that had responded well to chemotherapy. Mr. S was detained by U.S. Customs officials for four hours in December 2008 because they could not detect fingerprints. The Customs officials later determined that the man was not a security threat.
Tan says people being treated with Xeloda should carry a letter from their doctor that they are taking the medication if they want to travel to countries that require fingerprints for identification.
According to the letter in Annals of Oncology, other cancer patients taking the drug have reported similar side effects.
Foreign visitors have been asked to provide fingerprints at U.S. entry points for a number of years. The images are matched with millions of visa holders to detect whether the visitor has a visa under a different name; visitors' fingerprints are also compared to fingerprints of criminals, Tan says in the letter. It's "uncertain'' how long people would have to take the drug for their fingerprints to disappear. It's possible, he adds, that a growing number of people treated with the drug could experience the same problem and all should "prepare adequately" before traveling to avoid the "inconvenience" experienced by his patient.
"Mr. S" did not know his fingerprints had disappeared, according to Tan.
Xeloda is indicated for the treatment of breast and colorectal cancers. One of its side effects is be a condition known as hand-foot syndrome. Symptoms include swelling, redness, tingling, numbness, and pain of the hands and/or feet; the skin can peel, bleed, and develop ulcers or blisters.
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DIABETES DRUG PROVES USEFUL FOR MS
An FDA-approved drug which is currently used for diabetes treatment has been found to show some protective effects in the brains of patients with RELAPSING REMITTING MULTIPLE SCLEROSIS, according to researchers.
This finding is based on a small, double-blinded clinical trial in which patients with relapsing remitting multiple sclerosis were assigned to take the drug pioglitazone or a placebo. Patients continued their normal course of therapy during the trial.
The researchers initially carried out standard neurological and MRI scans to provide baseline values for lesions typically seen in MS patients. The patients were evaluated every two months, and blood samples were taken. Repeat MRI scans were done after five months and again after one year.
Patients taking the drug showed significantly less loss of grey matter over the course of the one-year trial than patients taking placebo.
Of the 21 patients who finished the study, patients taking the medicine did not show any adverse reactions. They found taking pioglitazone, which is administered in an oral tablet, easy.
"This is very encouraging. Grey matter in the brain is the part that is rich in neurons. These preliminary results suggest that the drug has important effects on neuronal survival," said Douglas Feinstein, research professor of anesthesiology at University of Illinois/Chicago.
The researchers revealed that they focused on pioglitazone because of its known anti-inflammatory effects. They used primary cultures of brain cells to show that pioglitazone reduced the production of toxic chemicals called cytokines and reactive oxygen species, the molecules that are believed to be important in the development of symptoms in MS.
Feinstein's lab has shown that pioglitazone and other TZDs "can significantly reduce the clinical signs in mice with an MS-type disease.
The study has been published in the online edition of the Journal of Neuroimmunology.
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ENJOY YOUR SUMMER, EVERYBODY!
And if you have any thoughts of how this newsletter could be improved, please email me directly, at email@example.com