FDA approved leukemia drugs shows promise in ovarian cancer cells

The drug Sprycel, approved for use by the U.S. Food and Drug Administration in patients with chronic myeloid leukemia, significantly inhibited the growth and invasiveness of ovarian cancer cells and also promoted their death, a study by researchers with UCLA's Jonsson Comprehensive Cancer Center found.

The drug, when paired with a chemotherapy regimen, was even more effective in fighting ovarian cancer in cell lines in which signaling of the Src family kinases, associated with the deadly disease, is activated.

The study appears in the Nov. 10, 2009 edition of the British Medical Journal.

Ovarian cancer, which will strike 21,600 women this year and kill 15,500, causes more deaths than any other cancer of the female reproductive system. Few effective therapies for ovarian cancer exist, so it would be advantageous for patients if a new drug could be found that fights the cancer, said Gottfried Konecny, an assistant professor of hematology/oncology, a Jonsson Cancer Center researcher and first author of the study.

"I think Sprycel could be a potential additional drug for treating patients with Src dependent ovarian cancer," Konecny said. "It is important to remember that this work is only on cancer cell lines, but it is significant enough that it should be used to justify clinical trials to confirm that women with this type of ovarian cancer could benefit."

Recent gene expression studies have shown that about one-third of women have ovarian cancers with activated Src pathways, so the drug could potentially help 7,000 ovarian cancer patients every year.

In this study, the UCLA team tested the drug against 34 ovarian cancer cell lines and they conducted genetic analysis on all cell lines. Through these analyses, the researchers were able to identify genes that predict response to Sprycel. If the work is confirmed in human studies, it may be possible to test patients for Src activation and select those who would respond prior to treatment, personalizing their care.

"We were able to identify markers in the pre-clinical setting that would allow us to predict response to Sprycel," Konecny said. "These may help us in future clinical trials in selecting patients for studies of the drug."

Sprycel is what is known as a "dirty" kinase inhibitor, meaning it inhibits more than one pathway. Konecny said it also inhibits the focal adhesion kinase and ephrin receptor, also associated with ovarian cancer.

The next step, Konecny said, would be to test the drug on women with ovarian cancer in a clinical trial. The tissue of responders would then be analyzed to determine if the Src and other pathways were activated. If that is confirmed, it would further prove that Sprycel could be used to fight ovarian cancer. In studies, women would be screened before entering a trial and only those with Src dependent cancers could be enrolled to provide further evidence, Konecny said, much like the studies of the molecularly targeted breast cancer drug Herceptin enrolled only women who had HER-2 positive disease.

"Herceptin is different because we knew in advance that the only worked in women with HER-2 amplification," he said. "In this case, we don't clearly know that yet. The data reassure us that the drug works where the targets are over-expressed but we need more testing to confirm this."
The tests combining the drug with chemotherapy are significant because chemotherapy currently is the first line treatment for ovarian cancer patients following surgery. Because Sprycel proved to have a synergistic effect when combined with chemotherapy both made the other work better it may be possible to add the targeted therapy as a first line treatment if its efficacy is confirmed in future studies, adding a new tool to an oncologist's arsenal.

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Drugs to treat anemia in cancer patients linked to thromboembolism

Medications frequently given to cancer patients to reduce their risk of anemia are associated with an increased risk of deep vein thrombosis or pulmonary embolism, according to new research led by Dawn Hershman, M.D, M.S., co-director of the breast cancer program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center. The findings will be published online on Nov. 10, 2009 in the Journal of the National Cancer Institute .

The anemia-reducing medications, known as erythropoiesis-stimulating agents (i.e., erythropoietin and darbopoietin) or ESAs, stimulate red blood cell production and are intended to reduce the number of blood transfusions required during chemotherapy. However, concerns about the risks of deep vein thrombosis or pulmonary embolism (manifestations of venous thromboembolism) and mortality exist.

"This research answers important questions about outcomes of ESAs when used in long-term clinical practice with oncology patients," said Dr. Hershman, the Florence Irving Assistant Professor of Medicine and Epidemiology at Columbia University Medical Center, whose research is dedicated to examining cancer survivorship. "While ESAs were given to reduce the need for blood transfusions, a substantial reduction in the use of blood transfusions was not observed. However, an increase risk of deep vein thrombosis or pulmonary embolism was confirmed."

"This analysis confirms the association between ESAs and venous thromboembolism, which was observed in previous meta-analysis," said Dr. Hershman. "This new finding is significant because where the meta-analysis looked at pooled data from randomized clinical trials, this data is from community practice -- real-life clinical settings -- where you can often see things that wouldn't necessarily show-up in a short-term, 12-week study. Additionally, this analysis included data from more than 50,000 patients? including those with more advanced cancer or high-risk status, who therefore might not have been candidates for clinical trials."

Based on previous findings, in the spring of 2007, the FDA required a black-box warning on ESAs about the potential for venous thromboembolism, tumor promotion, and decreased survival in ESA users. The warning suggested limiting the use of ESAs to specific tumor types, durations, doses, and targeted hemoglobin levels. In addition, the Center for Medicare and Medicaid Services proposed eliminating or limiting coverage for ESAs as treatment for some cancers.

"But what is reassuring about our findings are that they don't show an increased risk of mortality when ESAs are given with chemotherapy," said Dr. Hershman.

Dr. Hershman and colleagues analyzed the association between use of ESAs and venous thromboembolism and overall survival in patients who were 65 years or older and diagnosed with colon, non-small cell lung, or breast cancer or diffuse large B-cell lymphoma, between 1991-2002. These cancers were chosen because they were thought to be common cancers for which ESAs were frequently used. Patients were identified in the Surveillance, Epidemiology, and End Results?Medicare database, which at the time contained records of patients diagnosed with cancer in regions that represented approximately 14 percent of the U.S. population.

Results demonstrated that more patients who received an ESA developed deep vein thrombosis or pulmonary embolism, as compared to patients who did not. Overall survival was similar in both groups. The number of patients receiving ESAs increased approximately 10-fold from 1991 through 2002, with approximately 50 percent of patients with advanced cancer undergoing chemotherapy receiving ESAs by 2002. The rate of blood transfusion per year during the same time period, however, remained constant at 22 percent.

"Further efforts at monitoring use and long-term toxicity of expensive oncology drugs should be put in place to ensure that for any drug the benefits outweigh the risks in community practice," the authors write in the paper.

In the JNCI paper, the authors note that ESAs may be of particular interest from a public policy perspective because of the costs associated with their use. Total U.S. sales of ESAs were $10 billion in 2006, accounting for a greater Medicare Part B expenditure than any other drug.

The Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital encompasses pre-clinical and clinical research, treatment, prevention and education efforts in cancer. The Cancer Center was initially funded by the NCI in 1972 and became a National Cancer Institute (NCI)?designated comprehensive cancer center in 1979. The designation recognizes the Center's collaborative environment and expertise in harnessing translational research to bridge scientific discovery to clinical delivery, with the ultimate goal of successfully introducing novel diagnostic, therapeutic and preventive approaches to cancer.

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Aastrom to Initiate Second Phase II Clinical Trial for Treatment of Severe Chronic Heart Failure

Aastrom Biosciences, Inc. , a leading developer of autologous cell products for the treatment of chronic cardiovascular diseases, today announced that the Company will initiate its second clinical trial for the treatment of dilated cardiomyopathy (DCM), a severe disease associated with chronic heart failure, after a positive 30-day review of Aastrom's Investigational New Drug (IND) submission by the U.S. Food & Drug Administration (FDA).

This second trial is a 24 patient U.S. Phase II clinical trial to evaluate the catheter delivery of Cardiac Repair Cells (CRCs) for the treatment of DCM. The new trial expands the Company's cardiovascular program that includes a U.S. Phase II IMPACT-DCM clinical trial evaluating the direct surgical delivery of CRCs. The FDA previously granted CRCs an Orphan Drug Designation for the treatment of DCM.

"Given the encouraging initial results in our surgical-based, open-label clinical trial, we are expanding our cardiovascular program to include a catheter-based delivery method for these critically ill patients," said Elmar R. Burchardt, M.D., Ph.D., Vice President, Medical Affairs of Aastrom. "Our catheter-based delivery method is less invasive than the surgical approach and therefore increases the number of potential patient candidates for CRC treatment. End-stage heart failure patients currently have limited therapeutic options other than heart transplantation and mechanical pump assist devices. By expanding the delivery options for CRCs to include the catheter delivery by cardiologists, we are complementing the surgical delivery by cardiac surgeons."

The randomized, controlled, prospective, open-label, Phase II study will seek to enroll 12 patients with ischemic DCM and 12 patients with non-ischemic DCM at two clinical sites in the U.S. Participants must have a left ventricular ejection fraction of less than or equal to 30% (60-75% is typical for a healthy person) and meet certain other eligibility criteria. All 24 patients will receive standard medical care and 16 of the patients (8 ischemic and 8 non-ischemic) will also be treated with CRCs via catheter injection. While the primary objective of this study is to assess the safety of CRCs delivered by catheter injection in patients with DCM, efficacy measures including heart failure stage and cardiac function parameters will also be assessed. Patients will be followed for 12 months post treatment.

There are currently 5.5 million people in the U.S. suffering from chronic heart failure. A subset of these patients has DCM, a chronic cardiac disease where expansion of the patient's heart reduces the pump function to a point that the normal circulation of blood cannot be maintained. Patients with DCM typically present with symptoms of congestive heart failure, including severe limitations in their physical activity and shortness of breath. DCM generally occurs in patients who have ischemic heart failure due to multiple heart attacks, though it can also be found in patients with non-ischemic heart failure caused by hypertension, viral infection or alcoholism. Patient prognosis depends on the stage of the disease but is characterized by numerous health problems and a very high mortality rate.

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Mylan Receives FDA Approval for Generic Version of Prevacid

Mylan Inc. today announced that its privately held Indian subsidiary, Matrix Laboratories Limited, has received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for Lansoprazole Delayed-release (DR) Capsules, 15 mg and 30 mg. This product is shipping immediately and will be sold under the Mylan Pharmaceuticals brand.

Lansoprazole DR Capsules are the generic version of Tap Pharmaceuticals’ proton pump inhibitor Prevacidآ® DR Capsules. The brand product had U.S. sales of approximately $3 billion for the 12 months ending June 30, according to IMS Health.

Currently, Mylan has 125 ANDAs pending FDA approval representing $84.1 billion in annual brand sales, according to IMS Health. Thirty-seven of these pending ANDAs are potential first-to-file opportunities, representing $19.2 billion in annual brand sales, for the 12 months ending June 30, according to IMS Health.

Mylan Inc. ranks among the leading generic and specialty pharmaceutical companies in the world and provides products to customers in more than 140 countries and territories. The company maintains one of the industry’s broadest and highest quality product portfolios supported by a robust product pipeline; operates the world’s third largest active pharmaceutical ingredient manufacturer; and runs a specialty business focused on respiratory and allergy therapies.

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New drug for small cell lung cancer?

Scientists from the Imperial College of London have identified a promising new drug for the treatment of an aggressive form of lung cancer; small cell lung cancer.

Small cell lung cancer forms about 15-20% of the total cases of lung cancer. It is the most aggressive form of cancer that occurs within the lungs and grows and spreads quickly, most often to the brain, liver and bones.

Prognosis is poos, with only a 3-6% 5-year survival rate amongst patients diagnosed with it. As it spreads so quickly, surgery is usually not an option, as it most likely will be in more than one location by the time the patient is diagnosed. Combination chemotherapy and radiotherapy is commonly used instead, but a lot of the time the tumours grow back and are resistant to treatment.

The new drug being tested (PD173074) has been found to kill small cell lung cancer tumours in 50% of the mice it was tested on. It works by preventing a certain growth hormone the cancer cells need (called FGF-2, which speeds up the cancer cells' growth and multiplication) from attaching to its' receptor sites on the cells. It also lowers the cells' resistance to standard chemotherapy.


The next step is to try the drug out on small cell lung cancer patients who cannot be operated on.

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New 3-drug combo may effectively treat multiple myeloma

Researchers from Dana-Farber Cancer Institute have found that a new three-drug combination can effectively treat patients newly diagnosed with multiple myeloma, a cancer of white blood cells in the bone marrow.

The three-drug combination has shown in a phase 1/2 clinical trial that it is a ‘highly effective regimen’ in the treatment of this form of cancer.

Paul G. Richardson, of Dana-Farber, who led the study, said that partial responses or better were seen in all of the 66 patients treated with the drug combination in the multi-center study, with 74 percent having a “very good partial response rate” in the phase 2 population.

The rate of complete or “near complete” responses to the therapy was also encouraging at 54 percent.

The regimen, known as RVD, combined the drugs Revlimid (lenalidomide), Velcade (bortezomib) and dexamethasone, which previously were found to be highly effective in multiple myeloma patients who had relapsed or no longer responded to first-line therapies.

Fifteen of the 35 newly diagnosed patients in the open-label phase 2 portion of the study subsequently underwent autologous (using their own blood-forming stem cells) transplants, a standard treatment for multiple myeloma “and did very well,” Richardson said.

For the entire group, after a median 19.3 months of follow up, the median time-to-progression (TTP) of the disease, progression-free survival (PFS), and overall survival (OS) had not yet been reached, according to the presentation.

The estimated TTP and PFS at one year are 76 percent, and the estimated one-year overall survival is 100 percent, the results showed.

Richardson says it was ‘particularly exciting’ to observe that the high response rate was not affected by the specific genetic characteristics of the patients’ disease.

Patients with so-called “adverse cytogenetics” are at higher risk for treatment failure and death, but in the current study the drug combination worked as well for them as it did in patients with more favorable cytogenesis features.

Richard said that the toxic side effects of the treatment were ‘manageable.’

“Our conclusion is that this is a highly effective regimen for newly diagnosed multiple myeloma patients. The combination has now gone into large phase 3 clinical trials, and we think it has the potential to be a new standard of treatment in multiple myeloma, ” Richardson said.

The results have been described in an oral presentation at the American Society of Hematology’s 51st annual meeting on Saturday, Dec. 5. (ANI)

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New drug shows promise for those with clotting disorders

A new study provides welcome news for patients with a common clotting disorder known as venous thromboembolism (VTE).

The condition is estimated to impact 62,000 Canadians and half-a-million Americans every year, and occurs when an abnormal clot forms in a vein and restricts the flow of blood, causing pain and swelling। In some cases, the clot may detach from its point of origin and travel through the heart to the lungs, causing a potentially fatal condition known as a pulmonary embolism।

Currently, patients with VTE are treated with a blood thinner known as warfarin, which has many burdensome interactions with other medications and foods and requires frequent monitoring of the dosage.

However, this study published today shows that an oral drug called dabigatran etexilate, which does not have these disadvantages, is as safe and effective as warfarin for combating VTE.

To compare the two drugs, an international team of researchers led by Sam Schulman, a professor of medicine at the Michael G. DeGroote School of Medicine, conducted a randomized, double-blind trial of 2,539 patients with acute VTE.

Today, Schulman is scheduled to present this study to the annual conference of the American Society of Hematology in New Orleans, LA, and the New England Journal of Medicine will post the study on its web site. The study will be published in the Dec. 10 edition of the New England Journal of Medicine.

For six months, roughly half of the patients in the trial (1,274) were given a fixed dose of 150 mg of dabigatran etexilate twice daily, while the other half (1,265 patients) were given warfarin once daily.

The improvement seen in both groups from the treatments was similar. After six months of treatment, only 2.4 percent of the dabigatran etexilate group (30 patients) and 2.1 percent of the warfarin group (27 patients) experienced recurrent VTE.

The safety of the two drugs was also comparable. In the dabigatran etexilate arm, 205 patients experienced bleeding (including 20 patients with major bleeding) versus 277 patients in the warfarin arm (including 24 with major bleeding). Other possible side effects, including death, acute coronary syndromes, and abnormalities in liver function tests, were infrequent in the two groups.

"We are excited by these findings and feel that they will change the standard of care for venous thromboembolism, which affects a large number of our patients," said Schulman, a physician with the thrombosis service of Hamilton Health Sciences. "This study found that dabigatran is a safe and effective anticoagulant that does not require the routine monitoring or dose adjustments that are necessary with warfarin. In other words, patients can receive the same results in a more convenient manner."

The study was funded by Boehringer Ingelheim.

McMaster University, one of four Canadian universities listed among the Top 100 universities in the world, is renowned for its innovation in both learning and discovery. It has a student population of 23,000, and more than 140,000 alumni in 128 countries.

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New drug once used as bird poison shows promise for Multiple Sclerosis

An FDA panel is looking into the possibility that a new drug named Ampriva is helping people with Multiple Sclerosis. The drug is a reconfigured form of fampridine, which was originally used as a bird poison.

The Food and Drug Administration is looking at reports that the medication has helped people with MS actually walk with the help of the drug.

It's possible that the FDA will put this on the fast track because of the positive reports.

The new drug is different because it improves the nervous system function in people suffering from MS, and right now, the best that MS drugs can do is keep the progression of the disease from getting worse, and not change the already damaged nerves.

Ampriva is supposed to help protect the myelin which is damaged in people with MS. That damage is what affects movement and walking in some people with the disease.

So far, more than one-third of the people taking the new drug have been able to walk faster.

Dr. Andrew D. Goodman, director of the Multiple Sclerosis Center at the University of Rochester and the lead investigator in the clinical studies, said that "this can mean things like getting to the bathroom on time before having an accident, or getting across the street before the light changes."

Despite the obvious improvements, however, MS patients continue to get worse over time, Goodman's research shows. The results are slight at the moment.

Dr. Goodman says, "Things that people have described to me are, 'Look, I can get around the supermarket without having to hold on to the cart all the time,' or 'Just getting up that step between the garage and the house gives me independence.' "

The bird poision has been known to cause seizures and convulsions at high dosages.

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