NEW DRUG REGIMENS FOR HCV INFECTION

Twelve weeks of sofosbuvir and ribavirin treatment may be sufficient for sustained antiviral activity in untreated and pretreated patients with hepatitis C virus (HCV) genotype 1, 2, or 3, according to the findings of an open-label, phase 2 trial.

Edward J. Gane, MD, from the New Zealand Liver Transplant Unit, Auckland City Hospital and the Gastroenterology Department, Christchurch Hospital, both in New Zealand, and colleagues published their findings in the January 3 issue of the New England Journal of Medicine.

"The results from this study confirm that sofosbuvir, an oral nucleotide analogue polymerase inhibitor, combined with ribavirin, is a very effective treatment in patients infected with both genotype 1 and non–genotype 1 HCV, without cirrhosis," Dr. Gane told Medscape Medical News by email. "This regimen is very well tolerated: all oral, short-duration (only 12 weeks), and without any significant drug interactions or specific toxicity."

In the study, the authors treated patients as follows: 4 groups of 10 previously untreated patients with HCV genotype 2 or 3 infection each received sofosbuvir plus ribavirin for 12 weeks, with 3 groups also receiving peginterferon alpha-2a for 4, 8 or 12 weeks (groups 1 - 4); a group of 10 previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir alone for 12 weeks (group 5); a group of 10 previously untreated patients with HCV genotype 2 or 3 infection received sofosbuvir plus peginterferon alpha-2a and ribavirin for 8 weeks (group 6); a group of 10 patients with HCV genotype 1 infection who did not respond to previous treatment and a group of 25 previously untreated patients with HCV genotype 1 infection both received sofosbuvir plus ribavirin for 12 weeks (groups 7 and 8).

Among the patients in groups 1 to 4, all 40 patients had undetectable HCV serum levels up to 48 weeks after treatment. In addition, all patients in group 6 had a sustained virologic response (SVR) at 12 weeks after the end of treatment and all 9 patients for whom data were available had an SVR at 24 weeks.

The authors excluded patients with positive tests for hepatitis B surface antigen, hepatitis B core immunoglobulin M antibodies, or HIV antibodies. In total, 6 (60%) of 10 patients in group 5 and 21 (84%) of 25 patients in group 8 had an SVR at 24 weeks after treatment, whereas only 1 (10%) of 10 patients in group 7 had an SVR.

Among the patients without SVRs at 24 weeks, deep sequencing revealed the presence of the S282Tmutation in only 1 patient; no other mutations at conserved sites were identified.

No patient was forced to discontinue treatment because of adverse events. The most common adverse events included headache, fatigue, insomnia, and nausea.

Regarding hematologic events, sofosbuvir monotherapy was associated with modest (0.54 g/dL) decreases in hemoglobin levels. Patients who received peginterferon were more likely to experience hematologic abnormalities, and the degree of changes in hemoglobin levels was more severe among these patients.

Similarly, neutropenia and thrombocytopenia were only observed in patients who received interferon. No grade 3 or 4 elevations of bilirubin levels were observed, and only a single patient (in group 8) relapsed within 2 weeks after the end of treatment and displayed increased alanine aminotransferase levels.

Remaining Questions

In an email to Medscape Medical News, Dr. Gane identified several questions that remain to be addressed: "Will the excellent efficacy and tolerability in this phase 2 study be confirmed in the larger phase 3 studies, which contain patients with cirrhosis?" Dr Gane asked. "Which other antiviral agent should be combined with sofosbuvir to improve efficacy in treatment-experienced patients? Can such short-duration, all-oral therapy be administered in the community, thereby increasing treatment access?"

Donald M. Jensen, MD, director of the Center for Liver Diseases, the University of Chicago, Illinois, who was not involved in the study, noted that the treatment groups were small and fairly homogenous, thus requiring validation in larger, more representative cohorts. "We also need to know why prior interferon treatment failure predisposes to relapse but not on-treatment response and why this is more common in genotype 1a subjects (though few genotype 1b subjects were included in the present investigation)."

Dr. Jensen told Medscape Medical News by email: "Can this be overcome with longer treatment durations or combination with other antivirals? We also need to understand how ribavirin prevents relapse…a question that has plagued us for decades."

Ira M. Jacobsen, MD, chief of the Division of Gastroenterology and Hepatology from Cornell University in New York, also noted that the mechanism of ribavirin's role remains unclear. "Whether 12 weeks of sofosbuvir plus ribavirin will really provide 100% SVR rates in genotypes 2 and 3 remains to be answered by larger trials that are ongoing," Dr. Jacobson told Medscape Medical News by email. "Also unanswered is what will be required to achieve satisfactory SVR rates, preferably similar to naive patients, in nonresponders to previous peginterferon and ribavirin therapy. Optimization in genotype 1–naive patients is also a question."

GASTRIC CANCER RISK WITH PERNICIOUS ANEMIA

Patients with pernicious anemia have an increased relative risk of developing gastric cancer, a meta-analytic review of relevant studies confirms.

The authors estimate a pooled gastric cancer incidence in pernicious anemia of 0.27% per person-years.

Although a risk of gastric cancer in relation to pernicious anemia is reported in the literature, the studies differ from each other in terms of sample size and methods for the identification of gastric cancer used during the follow-up period, said Dr. Bruno Annibale and colleagues from University Sapienza, Rome, Italy in a report online December 10 in Alimentary Pharmacology & Therapeutics.

"Gastric cancer is the most severe long-standing complication of pernicious anemia and, to our knowledge, this is the first systematic review on the estimate of gastric cancer incidence-rate," they note.

Through a literature search, the researchers identified 27 articles published between 1950 and 2011 that reported the incidence of gastric cancer in pernicious anemia.

In meta-analysis, the overall gastric cancer relative risk with pernicious anemia was 6.8 (95% CI 2.6 - 18.1).

Among a total of 22,417 patients, 417 new cases of gastric cancer were identified in 157,319 person-years of follow-up, corresponding to an overall pooled gastric cancer incidence-rate per person-year of 0.26%, with a range between 0% and 1.2%.

When the researchers considered only the six studies with active follow-up protocols involving gastroscopy and histology, the pooled gastric cancer incidence-rate per person-years was 0.27% (95% CI 0.25 - 0.29), corresponding to seven new gastric cancer cases observed in 2,563 person-years.

In their paper, the authors note that the range of annual incidence rates for gastric cancer in pernicious anemia overlaps that reported in the literature for patients with atrophic gastritis, which is between 0% and 1.8% per year.

In email to Reuters Health, study co-author Dr. Edith Lahner said an "important take home message is that patients with pernicious anemia should be considered patients with atrophic gastritis, a condition at higher risk for gastric cancer, in which regular endoscopic-histological monitoring seems to be of benefit."

She noted that an expert panel advised an interval of every three years, in a paper by Dinis-Ribeiro et al in Endoscopy this year.

"In other words, the atrophic gastritis associated with pernicious anemia seems not to be all that different from the atrophic gastritis without pernicious anemia," Dr. Lahner said.

In their paper, the authors point out that almost half of the studies they included in their analysis were of low or very low quality, based on the Newcastle-Ottawa Quality Scale for cohort studies, which permits a critical appraisal of data.

"Although the 27 included studies showed similar incidence rates for gastric cancer, clinical and methodological heterogeneity was present," they say. Ten studies were retrospective (37%), and hospital records were often the sources of patients for these studies. Nonetheless, they say the incidence-rates of gastric cancer were similar among the studies irrespective of the study design and the source of patients.

The overlap of the pooled gastric cancer incidence per person-year of 0.27%, calculated from the six studies with active follow up by gastroscopy and histology, and the overall estimate obtained by considering all studies supports the "robustness of our analysis," the authors say.

"Thus, the main finding of this systematic-review," they say, "is the similarity of the incidence-rates of gastric cancer, which are remarkably stable among all studies despite major heterogeneity between individual studies in terms of their design (country of study location, sources of selection of participants, sample size, type and methods of follow-up, methods for identification of gastric cancer)."

"At this point," Dr. Lahner said, "we need further studies to determine the extent of the gastric cancer risk and the usefulness and time scheduling of follow-up in patients with pernicious anemia."

In their paper, the authors say the increased risk for gastric neuroendocrine tumors in patients with pernicious anemia "could represent an additional potential rationale for endoscopic surveillance in these patients."

The study was supported by grants from the Italian Ministry for University and Research, PRIN 2007 and from University Sapienza of Rome 2010-2011 Italy. The authors have declared no conflicts of interest.

NEOADJUVANT CHEMOTHERAPY FOR ALL WOMEN UNDER 35?

Neoadjuvant chemotherapy might be particularly critical for very young women with certain early breast cancers because of biologic differences in their tumors, according to research presented here at the 35th Annual San Antonio Breast Cancer Symposium.

"I would personally approach all young women with these cancers by suggesting neoadjuvant chemotherapy," said lead investigator Sibylle Loibl, MD, PhD, from the University of Frankfurt in Germany. "Some people think they don't need chemotherapy at all, but I think they do," she explained.

"Breast cancer in the very young woman seems to be different.... There is something behind age that drives the biology of the cancer and makes it more chemo-responsive," she noted.

In a meta-analysis of 8 trials involving 8949 patients, Dr. Loibl and her colleagues found that women younger than 35 years were more likely to achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy than women 36 to 51 years (23.6% vs 17.5%) and than women older than 51 years (13.5%; P < .0001).

Additionally, those with a pCR saw benefits in both disease-free survival and local recurrence-free survival, she said.

The superior pCR rate in young women after chemotherapy was driven by better pCR in 2 types of tumors: triple-negative tumors and luminal-like tumors, she added.

Specifically, women 35 years and younger achieved higher rates of pCR in triple-negative tumors than women 36 to 51 years (45% vs 35%) and than women older than 51 years (25%; P = .004).

Similarly, women 35 years and younger achieved higher rates of pCR in luminal-like tumors than women 36 to 51 years (approximately 11% vs 8%) and than women older than 51 years (6%; P = 0.013).

She said she expects the findings will influence clinical practice.

"I think the luminal-like patients, when they're very young, will be treated more often now with chemo. For women with triple-negative tumors, it's reassuring; we can tell them you have an almost 50% chance that everything will be gone and you'll have an excellent survival," she said.

All subjects in the meta-analysis received neoadjuvant anthracycline/taxane–based chemotherapy, and some received trastuzumab.

Generally, "in younger women, we tend to be more aggressive with chemotherapy," said Carlos Arteaga, MD, PhD, associate director of clinical research and director of the breast cancer program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, during a meeting press conference.

"The importance of this study is that it suggests there are some biological differences that go beyond luminal B that we have to study," he said.

Dr. Loibl and Dr. Arteaga have disclosed no relevant financial relationships. Study coauthor Gunter von Minckwitz, MD, PhD, reports being a consultant/advisor for sanofi-aventis, Roche, Amgen, AstraZeneca, Boehringer, and Eisai; and conducting scientific studies/trials for Amgen, Pfizer, GSK, sanofi-aventis, Roche, Novartis, BMS, Celgene, Cephalon, Boehringer Ingelheim, and Eisai. Coauthor Carsten Denkert, MD, reports receiving grant/research support from Siemens Medical Solutions and Sividon Diagnostics; consulting for Celgene, Amgen, and Sividon; and being a shareholder in Sividon Diagnostics. Coauthor Christian Jackisch, MD, reports being on the speaker's bureau for Roche and GSK. Coauthor Michael Untch, MD, reports receiving grant/research support from and being a consultant for Bristol-Myers Squibb and Amgen.

The Weight-Loss Nutrient You're Not Eating

Fiber: Weight-loss superfood?The U.S. often isn't the first nation to come to mind when you think of countries with healthy eating habits to adopt, but it turns out we may be influencing how our friends across the Atlantic dine.

The "all things fiber" trend taking over American supermarkets is also on the rise in Spain, Germany, Poland, and the U.K., where 62 percent of people say consuming enough fiber is important, a new European report found. Fiber even trumps calories, as only 56 percent said reducing calories was important.

This study intrigued me because while there are a number of foods with fiber added on the market-everything from pasta to yogurt-the latest nutrition data indicates that the average intake in the United States is less than half the recommended 14 grams per 1,000 calories (which works out to roughly 25 grams a day for women and 38 for men). And when I talk to my clients, most don't know much about this nutrient, other than it's generally good for you.

In a nutshell, fiber is a type of carbohydrate that your body can't digest or absorb, and there are two primary types: soluble and insoluble. Soluble is the soft, sticky type found in oats, barley, beans, and the "meat" of fruits, which helps to lower cholesterol and soften waste so it can pass through your system more easily. Insoluble is the tough type, found in whole wheat and the skin, stalks, and seeds of fruits and veggies, that helps to push waste through the GI tract and improve bowel regularity.

Fiber also has a number of weight-control benefits, which I've often touted on this blog. First, it fills you up, but because you don't break it down and absorb it into your bloodstream, you don't have to worry about burning off fiber in order to prevent it from getting socked away in your fat cells.

There is also some research showing that for every gram of fiber you eat, you eliminate about seven calories. That means if you gobbled 30 grams a day, it would essentially "cancel out" 210 of the calories you ate, which could result in shedding up to 20 pounds in a year's time.

Lastly, fiber has been found to slow the digestion and absorption of other carbs, which results in a slower, steadier rise in blood sugar and a delay in the return of hunger.

RELATED: In addition to fiber, be sure you're eating these eight super nutrients that help you slim down.

But fiber's powers don't stop at weight loss. It may also reduce the risk of death from any cause, according to a recent paper in the Archives of Internal Medicine. Women who ate about 25 grams of fiber a day were 22 percent less likely to die during the nine-year study than those who ate only 10 grams daily. And the risk of death from heart disease, infections, and respiratory diseases was reduced by as much as 50 percent in in the high-fiber eaters, with the greatest benefit seen from consuming grains. Pretty powerful stuff!

To boost your intake and hit the daily target, I recommend bulking up on naturally fiber-rich foods, primarily fruits, veggies, whole grains, beans, and nuts. Just a cup of raspberries, a cup of black bean soup, a medium orange, and an ounce of almonds packs more than 25 grams, so meeting the recommendation doesn't require a drastic change in your diet.

Some good general rules of thumb for upping your intake include:

• Choose more fruits with edible seeds, skins, and membranes, including apples, raspberries, and oranges.
• Reach for veggies with tough stalks and edible skin, such as artichokes and broccoli.
• Opt for whole rather than refined grains. Oats, barley, quinoa, brown and wild rice, and 100% whole-wheat versions of bread, pasta, and crackers are good options.
• Replace meat with beans or lentils at least five times a week.
• Snack on nuts and seeds, or use them to garnish salads, stir-fries, cereal, and yogurt.

Oh, and one more thing: As you increase your fiber intake, be sure to drink plenty of extra water. It's key to help the fiber move through your system. Too little H2O and too much fiber can be a recipe for bloating and constipation, or a pretty uncomfortable tummy ache!

CELL PHONE ADDICTION

Cell phone use and text messaging can become as addictive as any other behavior, such as compulsive shopping, gambling, and overeating, new research shows.

Investigators from Baylor University in Waco, Texas, found that both materialism and impulsiveness drive addictive tendencies toward cell phone use and text messaging.

"People understand substance addictions. They understand that we can take a drug that impacts parts of our brain and reinforces the pleasure principle, so we're addicted to that particular substance. But it's no different with behavioral addiction," said lead investigator James Roberts, PhD, in a video clip in which he discussed the study.

"We get some kind of reward from the use of our cell phone that produces pleasure — a lot of dopamine and serotonin in our brain — that keeps us coming back. So I think, and the research tells us, that behavioral addictions like cell phone addiction are just as real as substance addiction."

The article was published online November 17 in the Journal of Behavioral Addictions.

Materialism, Impulsiveness

The study included 191 business students at 2 US universities who completed a paper and pencil survey administered during class.

The questionnaire took approximately 15 minutes to complete and contained scales that measured materialism, impulsiveness, and mobile phone and instant messaging use.

Addictive tendencies toward mobile phone use and instant messaging were measured by mobile phone technology addiction (MPAT) and instant messaging technology addiction (IMAT) scales; responses were recorded on a 7-point Likert scale.

Mean scores for MPAT and IMAT were 5.06 and 2.52, respectively.

Impulsiveness was measured using Puri's 12-item scale, in which students were asked to rate how well 12 adjectives described them. The mean impulsiveness score was 3.2.

Materialism, best understood as the importance placed on worldly possessions, was measured using Mowen's 4-item scale. For this scale, respondents were asked to rate how accurately 4 personality traits described them.

On each of the respective scales, a higher score reflected a higher level of dependency, impulsiveness, or materialism.

Greater Potential for Addiction?

Results showed that both materialism ( P < .001) and impulsiveness ( P = .029) significantly predicted MPAT scores. Similarly, materialism ( P = .001) and impulsiveness ( P = .029) significantly predicted IMAT scores.

"Note that the impact of materialism on either addictive behavior is large relative to that of impulsiveness," the authors write.

The larger effect that materialism had on cell phone use in the current study relative to texting may also reflect the fact that cell phones are a sign of conspicuous possession.

In contrast, texting may be seen more as a private engagement and does not signal any particular status.

Dr. Roberts noted that whenever people display addictive behavior, it has negative effects on quality of life.

With cell phone and texting addiction, "it's an opportunity cost, so we are crowding out so many more important activities, including family and friends and other pursuits, that might bring us true happiness," he said.

Furthermore, cell phones are becoming "increasingly dangerous," because they offer more and more opportunities to interact with them, so their potential for addiction is greater, Dr. Roberts added.

Caution Warranted

Petros Levounis, MD, Columbia University College of Physicians and Surgeons, New York City, toldMedscape Medical News that gambling and compulsive sexual behavior come closer to the definition of frank addiction than cell phone and texting behaviors.

"We also have a long way to go before we develop reliable diagnostic criteria [for cell phone addiction and texting] to guide us in further research and clinical practice," he added.

On the other hand, Dr. Levounis does believe that the symptoms of those with these new technological addictions "share a lot of similarities with the more classic addictions of alcohol and drug abuse."

Journal editor Zsolt Demetrovics, PhD, Eötvös Loránd University, Budapest, Hungry, agreed that excessive use of cell phones and texting has similar characteristics to other addictions.

On the other hand, Dr. Demetrovics was uncertain whether overuse of cell phones should be viewed in the same light as a classic addiction.

"To consider something as a disorder or illness, the behavior must impair one's life significantly. And at this moment, we do not see these dramatic consequences in a large population," he told Medscape Medical News.

Nevertheless, Dr. Demetrovics believes it is important to pay attention to these behaviors, especially because they can cause some harm.

"But we should not overdramatize them as serious illnesses," he emphasized.