INTERMITTENT ANDROGEN SUPPRESSION AS EFFECTIVE AS CONTINUOUS TREATMENT FOR PROSTATE CANCER

Intergroup trial shows that intermittent androgen suppression is non-inferior to continuous androgen deprivation in men with PSA recurrence after radical therapy

In men with PSA recurrence after radical radiotherapy, intermittent androgen suppression has been suggested by phase II trials to improve quality of life (QoL) but effects on survival were unknown. In the NCIC CTG PR.7/SWOG JPR.7/CTSU JPR.7/UK intercontinental CRUKE/01/013 randomized phase III trial, investigators compared intermittent androgen suppression vs continuous androgen deprivation to test for non-inferiority with respect to overall survival.

Eligible men had rising PSA > 3.0 ng/ml more than one year after radical radiotherapy, either initial or salvage, for localized prostate cancer. Patients could receive up to 1 year of neo/adjuvant androgen deprivation therapy. Stratification factors were time since radical radiotherapy, initial PSA, prior radical prostatectomy and prior androgen deprivation therapy. Intermittent androgen suppression was delivered for 8 months in each cycle with restart when PSA reached >10 ng/ml off treatment. Primary endpoint was overall survival; secondary endpoints included time to hormone refractory state, QoL, cholesterol/HDL/LDL, duration of treatment/non-treatment intervals, time to testosterone and potency recovery. The independent Data and Safety Monitoring Committee recommended halting the trial after a planned interim analysis demonstrated that a pre-specified stopping boundary for non-inferiority was crossed.

Investigators randomized 1,386 patients, 690 to intermittent and 696 to continuous androgen deprivation. Arms were balanced for important baseline factors. Median follow up was 6.9 years. Intermittent androgen suppression patients completed a median of 2 x 8 month cycles. A total of 524 deaths were observed (268 on intermittent vs 256 on continuous androgen deprivation). Median overall survival was 8.8 vs 9.1 years on intermittent and continuous androgen deprivation arms, respectively (p=0.009). The intermittent androgen suppression arm had more disease related (122 vs 97) and fewer unrelated (134 vs 146) deaths. Time to the hormone refractory state was statistically significantly improved on the intermittent androgen suppression arm (p=0.024). Intermittent androgen suppression patients had reduced hot flashes, but otherwise there was no evidence of differences in adverse events, including myocardial events or osteoporotic fractures.

The authors, who presented results at the fourth annual Genitourinary Cancers Symposium (17-19 February 2011, Orlando, USA), concluded that in men with PSA recurrence after radical radiotherapy, intermittent androgen suppression, given as described herein, is non-inferior to continuous androgen deprivation with respect to the overall survival.

The Genitourinary Cancers Symposium was co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

Flu Season is Here

I've noticed everyone around me getting sick lately (I seem to have become mostly immune to colds and the flu in the last couple of years), so I took a look at Google Flu Trends. Lo and behold, the United States is currently near peak flu incidence for the 2010-2011 season. Here's a graph from Flu Trends. This year's trend is in dark blue:


Flu Trends also has data for individual US states and a number of other countries.

It's time to tighten up your diet and lifestyle if you want to avoid the flu this year. Personally, I feel that eating well, managing stress effectively, and taking 2,000 IU of vitamin D3 per day in winter have helped me avoid colds and the flu.

5 health reasons to not quit coffee

By Kerri-Ann Jennings, M.S., R.D., Associate Nutrition Editor atEatingWell Magazine

I really like coffee. The morning ritual of brewing a cup, the smell that perks me up before I take a sip and, of course, the flavor all make it my favorite beverage aside from water (water’s delicious!). As a registered dietitian and a nutrition editor for EatingWell Magazine, I know that coffee is fine in moderation. It has lots of antioxidants and is low in calories if you don’t load it up with cream and sugar. Nonetheless, I always feel slightly guilty about drinking it—you know, in a “it’s so good, it must be bad” kind of way.

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Which is why I’m always delighted to hear of new reasons that coffee is good for your health...and there are plenty! Over 18,000 studies on coffee have been published in the past few decades, revealing these benefits, many of which Joyce Hendley wrote about in the March/April issue of EatingWell Magazine:

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1. It protects your heart: Moderate coffee drinkers (1 to 3 cups/day) have lower rates of stroke than noncoffee drinkers, an effect linked to coffee’s antioxidants. Coffee has more antioxidants per serving than blueberries, making it the biggest source of antioxidants in American diets. All those antioxidants may help suppress the damaging effect of inflammation on arteries. Immediately after drinking it, coffee raises your blood pressure and heart rate, but over the long term, it actually may lower blood pressure as coffee’s antioxidants activate nitric acid, widening blood vessels.

2. It diverts diabetes: Those antioxidants (chlorogenic acid and quinides, specifically) play another role: boosting your cells’ sensitivity to insulin, which helps regulate blood sugar. In fact, people who drink 4 or more cups of coffee each day may have a lower risk of developing type 2 diabetes, according to some studies. Other studies have shown that caffeine can blunt the insulin-sensitivity boost, so if you do drink several cups a day, try mixing in decaf occasionally.

Must-Read: 4 Diet-Busting Coffee-Shop Drinks (and What to Drink Instead)

3. Your liver loves it: OK, so the research here is limited, but it looks like the more coffee people drink, the lower their incidence of cirrhosis and other liver diseases. One analysis of nine studies found that every 2-cup increase in daily coffee intake reduced liver cancer risk by 43 percent. Again, it’s those antioxidants—chlorogenic and caffeic acids—and caffeine that might prevent liver inflammation and inhibit cancer cells.

4. It boosts your brain power: Drinking between 1 and 5 cups a day (admittedly a big range) may help reduce risk of dementia and Alzheimer’s disease, as well as Parkinson’s disease, studies suggest. Those antioxidants may ward off brain cell damage and help the neurotransmitters involved in cognitive function to work better.

5. It helps your headaches: And not just the withdrawal headaches caused by skipping your daily dose of caffeine! Studies show that 200 milligrams of caffeine—about the amount in 16 ounces of brewed coffee—provides relief from headaches, including migraines. Exactly how caffeine relieves headaches isn’t clear. But scientists do know that caffeine boosts the activity of brain cells, causing surrounding blood vessels to constrict. One theory is that this constriction helps to relieve the pressure that causes the pain, says Robert Shapiro, M.D., Ph.D., associate professor of neurology and director of the Headache Clinic at the University of Vermont Medical School.

Now, that’s not to say that coffee doesn’t have any pitfalls—it does. Some people are super-sensitive to caffeine and get jittery or anxious after drinking coffee; habitual coffee drinkers usually develop a tolerance to caffeine that eliminates this problem (but they then need the caffeine to be alert and ward off withdrawal headaches). Coffee can also disturb sleep, especially as people age. Cutting some of the caffeine and drinking it earlier in the day can curb this effect. Lastly, unfiltered coffee (like that made with a French press) can raise LDL cholesterol, so use a filter for heart health.

But if you like coffee and you can tolerate it well, enjoy it...without the guilt.

ENDOMETRIAL CANCER SURVIVAL BETTER UNDER SPECIAL CARE

Women with high-risk endometrial cancer who were treated by gynecological oncologists had significantly better survival than patients not receiving such care, but the same study found that in the United States, only about 20% of women with endometrial cancer are treated by these specialists.
The findings are published online in the Journal of Clinical Oncology.
"The survival benefit associated with care by a gynecologic oncologist may be explained by their better understanding of the disease process, resulting in more accurate staging, followed by adjuvant treatment if indicated," the authors explain. However, they and an outside commentator point out that the superior survival could be attributed to a "stage migration" effect.
Deaths Are Increasing
The study is important, say the researchers, because the number of annual deaths from endometrial cancer has doubled over the past 20 years.
As far as they are aware, it is the first large population-based study to evaluate the influence of subspecialty care on patients with endometrial cancer.
The team, led by John Chan, MD, from the University of California San Francisco, analyzed data on 18,338 women with endometrial cancer from 1988 to 2005, obtained from the Medicare and Surveillance, Epidemiology and End Results (SEER) database.
They found that 21.4% of these women received care from gynecologic oncologists.
Compared with the remaining women, the women who received care from gynecologic oncologists were older, had more lymph nodes removed, presented with more advanced cancer (stages III to IV), had higher-grade tumors, and were more likely to receive chemotherapy for advanced disease.
They were also more likely to undergo staging procedures with lymph node assessment and to receive chemotherapy.
They showed significantly better survival rates for high-risk disease.
For women with stage II to IV disease who received care from a gynecologic oncologist, 5-year disease-specific survival was 79%, compared with 73% for women who didn't receive such care (P = .001). The difference was even greater for women with advanced-stage disease (stage III to IV), where the 5-year disease-specific survival was 72%, compared with 64% (P < .001).
However, there was no difference in survival rates for women with early, stage I and grade 1 cancers. All of them had "excellent" overall survival, the researchers note, with a 5-year disease-specific survival of 95%.
"This is an important paper, as it suggests that patients with more advanced endometrial cancer who are managed by gynecologic oncologists experience a superior outcome," said Maurie Markman MD, vice president of patient care services and national director for medical oncology at Cancer Treatment Centers for America, in Philadelphia, Pennsylvania.
"However, one must be cautious in the interpretation of the data, as 'stage migration' may be playing an important role," Dr. Markman added. This would have the effect of making it appear that patients with more advanced disease have a superior outcome when managed by a gynecologic oncologist, when in fact it is possible that the process of being seen by a gynecologic oncologist and undergoing a more extensive staging procedure results in patients being upstaged (e.g., from stage I to stage II or stage II to stage III), he explained.
The authors concur. In a subset analysis, they found that after adjusting for the effect of surgical staging in women with stage III disease, care by a gynecologic oncologist was no longer associated with an improvement in survival (84.6% vs 84.4%; P = .6).
"The result of this subset analysis suggests that the effect of gynecologic oncologist care may be partially attributed to the comprehensive staging procedures and subsequent guidance to appropriate therapy for improving survival," they write.
However, for women with stage III to IV disease, the benefit of gynecologic oncologist care might be associated not only with comprehensive surgical staging, but also with cytoreduction of metastatic disease, Dr. Chan and colleagues note. They found that, in a subset of 1689 stage IV patients, care from a gynecologic oncologist improved survival from 52% to 63%, suggesting that cytoreductive surgery might play a role in the survival advantage.
Another factor that might be at play is that care by a gynecologic oncologist might be associated with better screening and early detection of other malignancies, the authors suggest. They cite a previous study (Am J Obstet Gynecol. 2008;198:86.e1-86.e8), which found that patients with endometrial cancer who were cared for by gynecologic oncologists were more likely to receive mammography and colorectal cancer screening, compared with a matched group of women with no history of cancer cared for by primary care providers.
The authors have disclosed no relevant financial relationships. Dr. Markman reports serving as a director, officer, partner, employee, advisor, consultant, or trustee for Boehringer Ingelheim Pharmaceuticals, Genentech, Amgen, Celgene, and Hana Biosciences; and a as speaker or a member of a speakers bureau for Eli Lilly.

Gluten-Free January Raffle Winners Selected!

Raffle winners have been selected and shirts are on their way. You know who you are. Thanks to everyone who participated and filled out the survey! For those who didn't, there's always next year.

Janine Jagger, Matt Lentzner and I are busy crunching the mountain of data we collected from the GFJ survey. We got 279 responses, which is remarkable for a survey of this nature.

Stay tuned for data!

DENOSUMAB FOR BONE METASTASES

Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma.

Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, Scagliotti GV, Sleeboom H, Spencer A, Vadhan-Raj S, von Moos R, Willenbacher W, Woll PJ, Wang J, Jiang Q, Jun S, Dansey R, Yeh H.

Joan Karnell Cancer Center, Philadelphia, PA; Hospital de Santa Maria and Instituto de Medicina Molecular, Lisboa, Portugal; Teaching Hospital Cochin, Paris, France; McGill University Health Centre, Montreal, Canada; Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil; University Hospital Motol, Prague, Czech Republic; University of Torino, Orbassano, Italy; HagaZiekenhuis-Leyenburg, Den Haag, the Netherlands; The Alfred Hospital, Melbourne, Australia; MD Anderson Cancer Center, Houston, TX; Kantonsspital Graubünden, Chur, Switzerland; Medical University of Innsbruck, Innsbruck, Austria; Weston Park Hospital, University of Sheffield, Sheffield, United Kingdom; and Amgen, Thousand Oaks, CA.

Abstract

PURPOSE This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma. PATIENTS AND METHODS Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading. CONCLUSION Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.

Oltipraz

Oltipraz is a drug that was originally used to treat intestinal worms. It was later found to prevent a broad variety of cancers (1). This was attributed to its ability to upregulate cellular detoxification and repair mechanisms.

Researchers eventually discovered that oltipraz acts by activating Nrf2, the same transcription factor activated by ionizing radiation and polyphenols (2, 3, 4). Nrf2 activation mounts a broad cellular protective response that appears to reduce the risk of multiple health problems.

A recent paper in Diabetologia illustrates this (5). Investigators put mice on a long-term refined high-fat diet, with or without oltipraz. These carefully crafted diets are very unhealthy indeed, and when fed to rodents they rapidly induce fat gain and something that looks similar to human metabolic syndrome (insulin resistance, abdominal adiposity, blood lipid disturbances). Adding oltipraz to the diet prevented the fat gain, insulin resistance and inflammatory changes that occurred in the refined high-fat diet group.

The difference in fasting insulin was remarkable. The mice taking oltipraz had 1/7 the fasting insulin of the refined high-fat diet comparison group, and 1/3 the fasting insulin of the low-fat comparison group! Yet their glucose tolerance was normal, indicating that they were not low on insulin due to pancreatic damage. The low-fat diet they used in this study was also refined, which is why the two control groups (high-fat and low-fat) didn't diverge more in body fatness and other parameters. If they had used a group fed unrefined rodent chow as the comparator, the differences between groups would have been larger.

This shows that in addition to preventing cancer, Nrf2 activation can attenuate the metabolic damage caused by an unhealthy diet in rodents. Oltipraz illustrates the power of the cellular hormesis response. We can exploit this pathway naturally using polyphenols and other chemicals found in whole plant foods.