CuraGen and TopoTarget Announce Initiation of NCI-sponsored Phase II Clinical Trial with PXD101 for Mesothelioma

CuraGen and TopoTarget Announce Initiation of NCI-sponsored Phase II Clinical Trial with PXD101 for Mesothelioma   asbestosisreview.blogspot.com/


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BRANFORD, Conn., June 20 /PRNewswire-FirstCall/ -- CuraGen Corporation (Nasdaq: CRGN - News) and TopoTarget A/S (Copenhagen Stock Exchange: TOPO) announced today the initiation of patient dosing in a Phase II clinical trial evaluating the activity of PXD101, a small molecule histone deacetylase (HDAC) inhibitor, for the treatment of mesothelioma. This trial is being sponsored by the National Cancer Institute (NCI) under a Clinical Trials Agreement with CuraGen for the clinical development of PXD101.


The Phase II clinical trial is an open-label study being led by Suresh Ramalingam, M.D., Assistant Professor of Medicine at the University of Pittsburgh School of Medicine in Pittsburgh, PA. Patients with unresectable malignant pleural mesothelioma, who have failed one prior line of chemotherapy, will be enrolled and receive PXD101 by intravenous infusion every three weeks. The primary endpoint for the study is response rate, with secondary endpoints evaluating safety and measuring both the time to treatment failure and survival. A total of approximately 37 patients are expected to be enrolled into this study at multiple sites across the United States.

"A significant amount of preclinical research suggests that HDAC inhibitors, including PXD101, alter the regulation of many genes, resulting in growth inhibition of human mesothelioma cells. Given the ability of HDAC inhibitors to down-regulate genes such as BCL-XL and VEGF and up-regulate cell-cycle regulating genes, including p21, we are excited to begin evaluating PXD101 as a potential treatment for this type of cancer," stated Dr. Ramalingam. "There are no proven treatment options beyond the first-line chemotherapy regimen for mesothelioma, highlighting the importance of evaluating promising therapeutics like PXD101 for this patient population."
Correlative pharmacodynamic studies will also be conducted to evaluate the potential inhibition of HDACs in mesothelioma tumor cells from patients enrolled in this trial. Evaluation of the genes regulating proliferation and apoptosis (programmed cell death), as well as acetylation of histone and non-histone proteins, will be performed.
About Mesothelioma
As many as 3,000 new cases of malignant mesothelioma are expected to be diagnosed in the United States in 2006. Mesothelioma is a type of cancer arising from the cells, known as mesothelium, with the majority of cancers beginning in the chest cavity. The incidence of mesothelioma increases with age and is rarely diagnosed in patients under 55 years old. Although environmental exposure to certain chemicals and radiation are believed to play a role in the development of mesothelioma, exposure to asbestos is believed to be the main cause of mesothelioma. The five-year survival rate for mesothelioma is approximately 10%, with an average survival of one to two years following diagnosis.
About PXD101
PXD101 is a promising small molecule HDAC inhibitor being investigated for its role in the treatment of a wide range of solid and hematologic malignancies either as a single-agent, or in combination with other active anti-cancer agents, including 5-fluorouracil (5-FU), carboplatin, paclitaxel and Velcade

Medical and Civil Justice Communities Mourn the Loss of Mesothelioma Advocate, Terry McCann

Medical and Civil Justice Communities Mourn the Loss of Mesothelioma Advocate, Terry McCannPosted By Tony Vieira
June 3, 2006

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LOS ANGELES, June 8 /PRNewswire/ -- Terry McCann, Olympic gold
medalist, Toastmaster CEO, and asbestos victims rights advocate, died
yesterday from malignant mesothelioma. As a wrestler, surfer,
environmentalist, coach, devoted father, and spokesman for asbestos cancer
patients, Mr. McCann dedicated his life to serving others. He was also a
director on The Pacific Heart Lung & Blood Institute (http://www.phlbi.org ), a
medical research foundation in Los Angeles.
"We mourn the loss of a giant," said Roger Worthington, a director on
PHLBI. "Terry was one of the toughest men I have ever known, with a heart
of pure gold. In his final days, Terry's only concern was for his family,
his friends, and other mesothelioma patients."

Terry was diagnosed with mesothelioma in April of 2005. He pursued
surgical, chemotherapy and radiation treatments, which regrettably failed
to retard the advancement of the tumor, which had wrapped around his right
lung. Despite access to the best available care, Terry endured unimaginable
pain in the last few months of his life.
"I will always remember Terry as a fighter. He knew what the future
held, but he never gave up," said Dr. Robert Cameron, Chief of Thoracic
Surgery at the David Geffen School of Medicine at UCLA. "We owe it to Terry
to continue his fight to make mesothelioma research a national priority,
including pain management."
Each year, mesothelioma strikes approximately 3,000 Americans. The
median survival for mesothelioma patients hovers between 9 months and 19
months, depending on the treatments, if any, the patient is able, both
physically and financially, to pursue.
Terry joined PHLBI as a director after he learned how little money had
been invested in finding a cure, despite the enormous wealth of the
asbestos companies and their history of knowledge of the hazards of
asbestos.
"Terry used to tell me that if the companies back in the 1950s had
invested a fraction of their wealth in finding a cure, instead of hiring
hack lawyers and quack doctors to dummy up phony research, or hide the
truth, he wouldn't be facing a death sentence now," recalled Mr.
Worthington, who represents the McCann family in a civil action pending in
Los Angeles.
Mr. McCann, a wrestling Hall of Famer, was exposed to asbestos in the
late 1950s during the construction of an oil refinery in Tulsa. At the
time, he was training for the 1960 Olympics in Rome. Despite recent knee
surgery, and the bad luck of missing a start time due to a scheduling
snafu, he managed to fight through the qualifying rounds and eventually win
the gold medal.
Sadly, on the day of Mr. McCann's death, the lone defendant in McCann's
asbestos lawsuit, Foster Wheeler Ltd., came out in favor of federal
legislation that would bar mesothelioma patients from pursuing their
constitutional rights to a jury trial. Mr. McCann testified in his
deposition that he was exposed to tons of asbestos that would rain down
like snow from Foster Wheeler's massive boilers and pressure vessels.
"Terry McCann's exemplary life is an inspiration to all of us. He grew
up in the mean streets of Chicago. His prospects were bleak; his father was
an elevator operator and alcoholic. Yet, thanks to his tireless pursuit of
the American dream, he went on to become a living legend," said Mr.
Worthington. "He will be remembered as a bullish advocate for corporate
accountability, an athletic icon and an American hero."
Terry is survived by his wife of 52 years, Lucille, 7 children, and 18
grandchildren. For more information about Terry's mission to protect the
constitutional rights of asbestos victims, see
http://www.mesothel.com/pages/mccann_lat.htm , including the television
commercial in which Terry objected to the "asbestos bail out" bill (S.
3274). For more information about The Pacific Heart Lung & Blood
Institute's mission to expand treatment options for victims of occupational
diseases, see http://www.phlbi.org .
The Pacific Heart Lung & Blood Institute, Inc.
11818 Wilshire Boulevard
Suite 200
Los Angeles, CA 90025
Telephone: (310) 622-4960
Telecopier: (310) 231-2131
e-mail: rcameron

Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma

California Asbestos Law Blog: Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma--

Largest-Yet Mesothelioma Study Shows Survival Benefit with New Drug

Largest-Yet Mesothelioma Study Shows Survival Benefit with New DrugPosted By Tony Vieira
June 4, 2006

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Largest-Yet Mesothelioma Study Shows Survival Benefit with New Drug

Key Words: chemotherapy, lung cancer, mesothelioma, pemetrexed. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Researchers with the largest phase III trial to date for mesothelioma, an aggressive cancer affecting the lining of the lung, reported results showing that patients on a new chemotherapy drug regimen live longer and have less pain than those on an older drug. The findings were announced at the annual meeting of the American Society of Clinical Oncology meeting in Orlando, Fla., on May 20, 2002. (NOTE: The final data were subsequently published in the July 15, 2003, issue of the Journal of Clinical Oncology; see the journal abstract).

Pemetrexed (brand name Alimta

How is Mesothelioma Treated?

How is Mesothelioma Treated?Posted By Tony Vieira
June 22, 2006

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Treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient's age and general health. Standard treatment options include surgery, radiation therapy, and chemotherapy. Sometimes, these treatments are combined.

Treatment includes:

SurgeryThis information is provided courtesy of The National Cancer Institute.

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New Mesothelioma Treatments

New Mesothelioma TreatmentsPosted By Tony Vieira
June 29, 2006

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Implantable Device May Offer Better Pain Management
National Cancer Institute

Patients with advanced cancer who used an implantable drug-delivery device to control their pain had better pain relief, fewer toxic side effects, and better survival than patients who received intensive medical pain management, researchers reported in the October 1, 2002, issue of the Journal of Clinical Oncology.

The multicenter trial involved 202 patients who were randomly assigned to two groups. One group received comprehensive medical management (CMM) for their pain. CMM is a more systematic approach to pain control than cancer patients typically receive. It involves a team of health care professionals with special training in pain management who search for the most effective pain medication for each patient by starting with the least toxic and only gradually moving up to medications with more side effects until the pain is relieved. CMM may also include the use of complementary methods of pain reduction such as relaxation, guided imagery, psychotherapy, and patient support groups.

The trial's second group received CMM plus the implantable device. Implantable drug delivery systems (IDDSs) deliver narcotic pain medications directly to the spinal fluid, using much smaller doses than are required when the same drugs are taken by mouth or injected. The device consists of a small, battery-powered, programmable pump implanted under the skin of the abdomen and connected to a small catheter. Although IDDSs have been in use since 1991, this was the first randomized trial to compare the device with CMM for cancer pain.

Upon entering the study, most trial participants were taking at least 250 milligrams per day of narcotic pain relievers, such as morphine. Many were also taking additional medications such as antidepressants and anticonvulsants for pain relief.

During the study, patients in the CMM-only group continued to take morphine or similar narcotic drugs by mouth, plus additional medications as needed. Most IDDS patients received morphine via the pump; the others received hydromorphone (Dilaudid). IDDS patients could take additional narcotics by mouth if necessary.

At study entry, all trial participants rated their pain as well as the side effects of their pain medication (such as sedation, clouded thinking, constipation, and fatigue) on scales from 0 (least) to 10 (worst). Both the CMM-only group and the CMM-plus-IDDS group had average pain scores of more than 7.5 at the start of the trial.

But four weeks later, pain scores for IDDS patients fell to an average of 3.7 (a 51.5 percent reduction). In CMM patients, average pain scores dropped to 4.8 (a 39 percent reduction). IDDS patients also experienced a 50 percent reduction in toxic side effects after four weeks. By contrast, in patients who received CMM alone, toxic side effects declined by 17 percent.

When the researchers looked to see how many individuals in each group lowered their pain and side-effects scores by 20 percent or more, they found that 58 percent of patients using the implantable device had achieved this level of relief compared with 38 percent of patients who received CMM alone.

Survival rates also differed. After six months, 54 percent of patients using the implantable device were alive, compared with 37 percent of those in the CMM-only group. The better survival among users of the implantable device may be partly explained by the fact that they experienced a larger reduction in toxic side effects, say the investigators, who were led by Thomas J. Smith, M.D., of the Medical College of Virginia in Richmond.

As many as 15 percent of cancer patients have pain that is not relieved by conventionally delivered narcotic pain medications, note the researchers. Previous studies have shown that fear of the side effects of these medications is an important reason why many doctors fail to prescribe them and many patients decline to take them.

"This is a well-designed study that shows a modest but real benefit from the use of an implantable pump for control of cancer pain," commented Mitchell Max, M.D., a pain control specialist at the National Institute of Dental and Craniofacial Research in Bethesda, Maryland. He added, however, that it is premature to conclude that implantable pumps are better for all patients with difficult-to-treat cancer pain. "We need more research to better define which subgroups of cancer patients will benefit the most from using these devices."

Experimental Cancer Drug Tarceva
Reuters, October 9, 2002

NEW YORK (Reuters Health) - OSI Pharmaceuticals Inc. is more confident than ever of the potential of its experimental cancer drug Tarceva (erlotinib HCl), even after the failure of a similar drug in a major clinical study this summer, OSI Chairman and CEO Dr. Colin Goddard told investors at the UBS Warburg Global Life Sciences conference here on Wednesday.

In August, AstraZeneca Plc. announced that adding its investigational non-small cell lung cancer (NSCLC) drug Iressa to standard therapy did not improve survival in a phase III trial of patients who had failed prior chemotherapy. The news raised concerns about a new class of cancer drugs expected to be effective with fewer side effects than other therapies.

Iressa is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. These kinds of drugs are believed to cause fewer adverse events because they target specific proteins associated only with tumors.

Since Tarceva is also an EGFR inhibitor, many industry watchers began to worry that the drug, which is still being evaluated in a phase III trial of NSCLC patients, might also fail to meet expectations.

But Dr. Goddard dismissed these concerns on Wednesday, noting that while similar, Iressa and Tarceva are structurally different. But more importantly, he said, the companies' approaches in evaluating their respective drugs are very different, as well.

Dr. Goddard told Reuters Health that in its failed trial, AstraZeneca was using doses of Iressa one-third to two-thirds of the maximum tolerable dose. OSI is using the highest tolerated dose of Tarceva.

Interestingly, he said, one of the side effects of Tarceva treatment is rash, and "what we find is when we produce rash, patients tend to do very well. In other words, there's a suggestion that pushing dose has real benefit in terms of survival."

"Hence, our whole rationale and belief is that we will see a differentiation between