The cancer drug Avastin, when used in combination with standard chemotherapy, is safe and can effectively treat an advanced form of one of the most common lung cancers, researchers report.

Previously it had been thought that this combination might have serious adverse side effects, including life-threatening bleeding, for patients with non-squamous non-small-cell lung tumors. However, this phase 4 trial, which used Avastin (bevacizumab) plus chemotherapy in a large population found these problems were minimal.

Phase 4 trials are done after a drug is on the market, to look for any new problems.

“Today we have a new option to treat non-squamous lung cancer, incorporating Avastin in chemotherapy regimens and in maintenance therapy,” said lead researcher Dr. Lucio Crino, director of medical oncology at S. Maria della Misericordia Hospital in Perugia, Italy.

“The practical implication is the possibility to incorporate Avastin with any chemotherapy regimen in the frontline therapy of metastatic non-squamous lung cancer,” he added.

The report, which is funded by the maker of Avastin, F Hoffman-La Roche Ltd., is published in the July 20 issue of The Lancet Oncology. The funder was involved in study design, coordination of data collection, data analysis, data interpretation, and writing of the report, the journal noted.

Advanced non-small-cell lung cancer is a common cancer that kills 1.18 million people every year worldwide, according to background information in the study. Avastin is a so-called monoclonal antibody that works by blocking vascular endothelial growth factor A, which stimulates the growth of the tumor’s blood supply.

When used as an adjunct to chemotherapy, Avastin had already shown cancer-fighting activity in two phase 3 trials, the researchers noted.

For the study, Crino’s team studied Avastin in more than 2,200 patients with advanced or recurrent non-squamous non-small-cell lung cancer. The patients were treated at centers in 40 countries around the world.

These patients were given the drug every three weeks along with standard chemotherapy, for up to six cycles. Patients were then treated with Avastin alone until the cancer began to progress (”maintenance” therapy).

The researchers reported few clinically significant adverse events, meaning that most were no greater than what one would expect in the general population. One percent of patients experienced bleeding in the lungs and 4 percent had bleeding, Crino’s group found.

Overall, 3 percent of the patients died due to adverse events associated with Avastin. These included 1 percent who had blood clots and 1 percent who suffered bleeding.

Other serious adverse events associated with Avastin were blood clots in the lungs and nosebleeds, low white blood cell counts, fever along with a low white blood cell count and deep vein thrombosis (DVT), all of which occurred in 1 percent of the patients.

Dr. Robert Pirker, from the department of medicine at the Medical University of Vienna in Austria, and author of an accompanying journal editorial, said that Avastin “can be safely given when certain precautions are taken.”

However, several issues remain to be determined, including the optimal dose and the role of maintenance therapy with Avastin, he said.

“In addition, it is unknown whether bevacizumab [Avastin] increases survival when added to cisplatin-based chemotherapy in patients with advanced non-squamous non-small-cell lung cancer,” Pirker said.

Overall, Avastin, like several other targeted agents have led to therapeutic advances in lung cancer, he added. “Hurdles in clinical development do occur but — as shown for bevacizumab — can be overcome,” Pirker said.

Another expert, Dr. Norman H. Edelman, chief medical officer at the American Lung Association, and professor of preventive medicine, internal medicine, physiology & biophysics at Stony Brook University in New York, called the study “very good bread-and-butter clinical research.”

The efficacy of the drug has been proven previously, he noted, but this study provides an in-depth analysis of Avastin’s safety profile under “real life” conditions, he added.

“Too often this step is shortcircuited in the rush to market of a new drug and we have to await the laborious collection of after-market data to find the real dangers of many new drugs,” Edelman said.

“So, the researchers and sponsors are to be congratulated for doing this study. They find that there are real deleterious side effects but that they are manageable, and conclude the drug is worth using under the proper circumstances,” he said.

Avastin is in the spotlight Tuesday for another reason, as well. U.S. regulators could rescind approval of the drug for the treatment of breast cancer, based on follow-up studies reported Friday that failed to show the medication shrank tumors or extended lives, according to published reports.

The Food and Drug Administration on Tuesday will ask a panel of outside experts to review the evidence on the Roche drug, the Associated Press said. It’s possible the FDA will withdraw approval of Avastin as a breast cancer treatment.

The drug is also approved for lung, colon, brain and kidney cancer.

Technorati Tags: Advanced Lung Cancer, Avastin

Swiss drugmaker Novartis AG won wider U.S. approval for its leukemia drug Tasigna to treat a rare form of the blood cancer at an earlier stage of the disease, the Food and Drug Administration said on Thursday.

Tasigna had previously been approved to treat adults with chronic myeloid leukemia, or CML, in patients who could not tolerate or were no longer responding to treatment with Gleevec, an older but highly effective Novartis drug.

The new approval could lead to significantly higher sales of Tasigna, known chemically as nilotinib.

In a clinical study presented at a major cancer meeting earlier this month, Tasigna fared better than Gleevec in a head-to-head trial, paving the way for the expanded approval.

About 44 percent of patients taking the newer Novartis pill had a major molecular response compared with 22 percent for Gleevec after 12 months.

A major molecular response is defined by a reduction of disease by 99.9 percent and has been associated with higher rates of long-term survival.

The side effects, or toxicity, seen with Tasigna were less severe than with Gleevec in the head-to-head study, researchers said when presenting the data.

Both Tasigna and Gleevec belong to a class of drugs called tyrosine kinase inhibitors, which deactivate messages that make leukemia cells malignant and kills them.

Bristol-Myers Squibb Co is hoping to win earlier stage approval for its similar CML drug Sprycel, which also topped Gleevec in a recent head-to-head trial.

Any long-term survival improvement the newer drugs can demonstrate over Gleevec would be impressive. The older drug increased the CML 10-year survival rate from less than 20 percent to up to 90 percent and transformed CML from a death sentence to a manageable disease for most patients.

“It’s important for companies to continue developing oncology drugs for earlier stages of the disease once they have demonstrated clinical effectiveness in resistant forms of cancer,” Dr Richard Pazdur, director of the Office of Oncology Drug Products for the FDA’s Center for Drug Evaluation and Research, said in a statement.

“This approach has the potential to increase the availability of an effective treatment to more patients,” he added.

(Reporting by Bill Berkrot; Editing by Tim Dobbyn)

Technorati Tags: blood cancer, Gleevec, leukemia drug, nilotinib, Novartis, oncology drugs, Tasigna

A drug being developed by Pfizer and Onyx and already in clinical trials against a range of cancers has shown in laboratory tests “a remarkable ability” to halt growth of a deadly type of brain tumor, U.S. scientists said on Tuesday.

Researchers from Georgetown Lombardi Comprehensive Cancer Center and the University of California said the experimental drug, called PD-0332991, may become a new treatment option for glioblastoma, the commonest and deadliest form of brain cancer.

Clinical trials to test the drug in patients with recurrent brain cancer are under development, they said in a study published in the journal Cancer Research.

“We don’t know how well this agent will perform in patients with glioblastoma but in the mice we studied we saw very impressive, durable effect,” said David James, a professor of neurological surgery at UCSF, who worked on the study.

“What is especially encouraging about this agent is that we found it can easily pass through the blood-brain barrier and access glioblastoma, and that there is already a simple test available for screening glioblastoma patients in advance to see whether or not they should be responsive to this therapy.”

Data from a recently-published study by The Cancer Genome Atlas Research Network, suggests about 90 percent of glioblastoma patients would be suitable candidates for the drug, he said.

PD-0332991, which Pfizer is developing under license from Onyx, is being tested in human trials for other cancers such as multiple myeloma and mantle cell lymphoma. It is a pill designed to shut down activity of molecules called cyclin-dependent kinases 4 and 6 (cdk4 and cdk6) that drive cell division.

“In normal cells these kinases are kept under exquisite control by a gene known as p16,” said Todd Waldman of Lombardi, who worked on the study with James.

“But in glioblastoma and other cancers, p16 is frequently deleted, and these two kinases are uncontrollably activated, which drives the cell to divide and form cancer.”

But the drug does not work if the cancer is missing a protein known as retinoblastoma (Rb). A test for Rb is already being used to screen patients for use of PD-0332991 in the ongoing clinical trials.

In their study James’s team implanted three different kinds of human glioblastoma directly into the brains of mice and then treated them with PD-0332991. They found the drug was able to get to the tumors and halt the cancer’s growth as long as the mice stayed on the drug.

Because PD-0332991 itself does not kill cancer cells — just halts their growth — the researchers then combined the drug with radiation and found the combination worked better than PD-0332991 alone. They also successfully tested the drug in mice in which glioblastoma had come back after treatment with temozolomide, a chemotherapy used in many cancer patients.

Technorati Tags: brain cancer, brain cancer drug, experimental drug, new treatment option for glioblastoma, PD-0332991, Pfizer

Adding chemotherapy to standard cancer-suppressing tamoxifen (also manufactured under brand name Nolvadex) can boost survival in postmenopausal women with the most common type of breast cancer, known as estrogen receptor-positive, and it’s best given before the tamoxifen regimen starts, according to a new study.

“Chemotherapy with Adriamycin adds to your survival benefit over and above what tamoxifen would do if you are postmenopausal and have positive lymph nodes and estrogen receptor-positive cancer [the most common type],” explained Dr. Kathy Albain, the lead researcher and professor of medicine at Loyola University Chicago Stritch School of Medicine.

And in another study, Albain found that screening breast tumors with an available multi-gene test spots patients who may not need this form of chemotherapy, despite fitting the standard profile.

Both studies are published online Dec. 10, the first in the journal The Lancet and the second in The Lancet Oncology. Albain is also due to present her findings Thursday at the annual San Antonio Breast Cancer Symposium in San Antonio, Texas.

In estrogen receptor-positive cancer, tumor cells carry many receptors on their surfaces to which estrogen can attach, fueling tumor growth. Tamoxifen works by blocking the receptors.

Experts have long debated whether women with estrogen receptor-positive cancers — whose growth is fueled by circulating estrogen — would get more benefit from having a chemotherapy regimen on top of tamoxifen.

Albain led a research team from multiple centers that followed nearly 1,500 breast cancer patients for up to 13 years, with a median (half longer, half less) of nearly nine years. All were past menopause and had hormone receptor-positive cancer that had spread to at least one lymph node in the armpit area.

Albain’s team assigned 381 women to tamoxifen alone, 587 to chemotherapy alone and 590 to both, with some receiving tamoxifen and chemo together and some in a sequential manner.

Tamoxifen was taken daily for five years. The chemo regimen used is called CAF, for “cyclophosphamide, Adriamycin and 5-fluorouracil.”

In all, after accounting for study dropouts, 1,460 women received treatment.

The combined treatments of chemo plus tamoxifen increased the women’s disease-free survival by 24 percent, Albain found. When her team looked at which delivery protocol worked best — simultaneous tamoxifen and chemotherapy or chemo followed by tamoxifen — the sequential approach was found to be better, giving slightly better disease-free survival.

Ten-year disease-free survival estimates were 57 percent for the combination group and 48 percent for the tamoxifen-only group, the researchers found.

However, women receiving chemo were more likely to have drops in white blood cells, important for fighting infections, the team noted. And they were also more prone to blood clots, congestive heart failure and other complications.

In a second study, Albain’s team analyzed whether a gene test, called Oncotype DX, could predict which women would benefit from chemotherapy. Genomic Health, which makes the test, helped fund the study, along with the U.S. National Cancer Institute.

The test, which Albain said is already widely used, is done on the tumor itself. “This puts 21 genes together and comes up with a score,” she said. The score — low, intermediate, high — predicts the risk of recurrence over 10 years if a woman used tamoxifen alone.

When the researchers performed the test on 367 specimens, they found a low score identified those women who may not need the chemo, despite the fact that they have cancer that spread to lymph nodes.

“This is a positive study, there’s no question,” said Dr. Joanne Mortimer, vice chair of medical oncology for the City of Hope Cancer Center in Duarte, Calif., of the first study. “This study tells us [that] if you have positive lymph nodes [and are postmenopausal with estrogen receptor-positive cancer], you should have both chemo and tamoxifen, because the survival was better.”

But, she added, “when you give everyone [who has the estrogen receptor-positive, node-positive breast cancer] chemotherapy, probably there are some who don’t need it.”

According to Mortimer, that’s why the gene test looks promising — it may spare some women from having to have chemo while ensuring that those who will benefit from the treatment get it.

Technorati Tags: breast cancer, chemo and tamoxifen, chemotherapy, Nolvadex, tamoxifen

Men who regularly get moderate exercise may have a lower risk of developing prostate cancer — including aggressive, fast-growing tumors, a new study finds.

Researchers found that among 190 men who underwent biopsies for possible prostate cancer, those who exercised moderately — the equivalent of three to six hours of walking per week — were less likely to be diagnosed with the disease.

Compared with their sedentary counterparts, these men were two-thirds less likely to have a biopsy positive for prostate cancer. In addition, men who got the equivalent of one to three hours of walking each week had an 86 percent lower chance of having an aggressive form of the cancer.

The findings, which appear in the current issue of the Journal of Urology, do not prove that exercise helps prevent prostate cancer. But they could offer men yet more incentive to get active.

“If you need one more reason to exercise, this could be one,” said senior researcher Dr. Stephen J. Freedland, of the Duke University Prostate Center and the VA Medical Center in Durham, North Carolina.

A number of studies have looked at the relationship between exercise and prostate cancer, and while most have pointed to a protective effect, about one-third have found no association, Freedland told Reuters Health.

One question has been whether the positive findings reflect a greater tendency of health-conscious exercisers to get screened for prostate cancer. This study avoided that issue, Freedland said, by focusing on men who were sent for biopsies after concerning findings from prostate specific antigen (PSA) testing or a digital rectal exam.

He and his colleagues found that among the 111 sedentary men in the study, half were diagnosed with cancer after biopsy. That compared with 27 percent of those men who got the equivalent of three to six hours of walking each week.

And among men diagnosed with prostate cancer, 51 percent of sedentary patients had more-aggressive cancer, versus 22 percent of those who had been mildly active — getting the equivalent of one to three hours of moderate walking per week.

Exercise itself remained linked to a lower risk of prostate cancer after the researchers accounted for a number of other factors, like age, weight and race.

Along with studies finding a relationship between exercise habits and lower prostate cancer risk, there is also research showing that the connection is biologically plausible, Freedland said.

For one, he noted, exercise has been shown to lower blood levels of testosterone and other hormones that may stimulate prostate tumor growth. Exercise is also believed to stimulate the immune system and the body’s natural antioxidant mechanisms, both of which may help prevent the development of prostate cancer.

SOURCE: Journal of Urology, November 2009.

Technorati Tags: antioxidant mechanisms, exercise and prostate cancer, prostate cancer

Weight loss and malnutrition are serious threats to patients battling cancer, who can find that their tumors or treatment sap their appetite, cause nausea and other side effects and block absorption the nutrients they do force down. Here are some tips from cancer specialists and dietitians to help:

• Try to eat five or six small meals throughout the day rather than three large ones.
• Cancer patients tend to need more protein than healthy people. Peanut butter crackers, yogurt and fruit, a hard-boiled egg and piece of toast all are good mini-meals.
• Drink between meals, not with them, to avoid filling up on liquid.
• Don’t try your comfort food if you’re vomiting. It may create an aversion.
• Foods high in fat or fiber make nausea last longer.
• White, bland foods tend to help with nausea, such as Cream of Wheat, mashed potatoes, cottage cheese.
• Odors often worsen nausea, and foods served at room temperature rather than warm tend to have milder odors.
• Fresh ginger about 30 minutes before eating also can take the edge off nausea, but not ginger flavoring common in many sodas. A study published last week found ginger capsules work, too.
• Certain cancer medications, particularly painkillers, cause constipation, so keep up the fiber whenever the nausea passes.
• Take special care to stay hydrated when diarrhea strikes. Bananas, rice, applesauce and toast are good options.
• Many patients find foods that once tasted good now taste metallic. Citrus sometimes counters that; try sucking lemon drops, or drinking lemonade with meals, or using citrus-based marinades. Other patients may have a treatment-caused, and correctable, zinc deficiency.
• Tell your doctor about any over-the-counter dietary supplements. Some, such as St. John’s wort, can cause dangerous interactions with numerous anti cancer medications. Even high amounts of acidic vitamin C can worsen stomach problems.
• Staying hydrated and eating foods moistened with sauces and gravies helps dry mouth; doctors also can prescribe an artificial saliva.
• High-protein, high-calorie milkshakes and canned supplements like Ensure help sneak in extra nutrients and are especially helpful for patients with mouth sores. Make your own with whole milk and a few tablespoons of dry milk or protein powder.
• Ask for a consultation with a dietitian who specializes in cancer before you start losing weight. Specially designated cancer centers have dietitians on staff, and insurance may cover other consultations if the doctor orders it. The American Cancer Society’s toll-free hot line — 1-800-ACS-2345 connects patients in the Southeast to dietitians on call, and will find nutrition answers for people elsewhere. To find nearby dietitians, try http://www.eatright.org.
• Look for recipes targeted to cancer patients. The cancer society posts some at http://www.cancer.org, and plans a new cookbook in July.

Technorati Tags: anti cancer medications, Cancer, Cancer nutrition, Cancer nutrition tips, dietary supplements, dietitian, start losing weight