he Food and Drug Administration has approved the first drug to treat the joint condition, gout, in more than 40 years.
The drug lowers uric acid in the blood of patients with gout. Gout is a common and painful form of arthritis that causes swollen, red and hot joints. It occurs when uric acid builds up in the blood because the body can't get rid of it fast enough, or because some people's bodies produce too much of it.
The condition is common in men over the age of 40 years old.
The new drug, Uloric, is made and marketed by Takeda Pharmaceuticals North America.
It will be available in 40- and 80-milligram tablets to be taken once a day, according to a company press release.
Showing posts with label treatment. Show all posts
Showing posts with label treatment. Show all posts
February 16, 2009
February 12, 2009
Cure for common cold in the making
Researchers who mapped the DNA of more than 100 different cold viruses said on Thursday they discovered a shortcut in their life cycle, which may explain why they can inflict misery so quickly.
They also believe they may find ways to design drugs to fight the rhinoviruses, which use their single gene to move rapidly from person to person, causing symptoms that range from irritating sniffles to pneumonia.
Instead of designing one drug to cure the common cold, several may be needed because the virus mutates so efficiently, said Dr. Stephen Liggett of the University of Maryland medical school, who led the study published in the journal Science.
"We may end up having four or five drugs," Liggett said in a telephone interview on Thursday.
The hope had been that it might be easy to fight the viruses, which sicken children on average 10 times a year and adults at least twice a year on average.
This is because any rhinovirus has just one gene, which in turn makes a giant protein that appears to do little or nothing until it gets chopped up into 11 smaller pieces by an enzyme called a protease.
Researchers tried to attack this big, clumsy protein before. "The first drug, the virus mutated around it," Liggett said. "But now that we have all the pieces we can begin to understand what areas are not so flexible. We can begin to do some more rational drug design."
For example. it might be possible to attack the protease -- an approach that has worked in fighting AIDS. "If we could inhibit that protease from cleaving that protein, maybe we could render all rhinoviruses ineffective," Liggett said.
Liggett's team also found the viruses take a shortcut in making the proteins, which probably speeds up their ability to make a person feel sick soon after infection.
Claire Fraser-Liggett, who directs the Institute for Genome Sciences and also worked on the study, called this a "new insight."
The viruses also swap genes promiscuously in the equivalent of viral sex, a process known as recombination. This helps them constantly change and adapt.
"We generally think of colds as a nuisance, but they can be debilitating in the very young and in older individuals, and can trigger asthma attacks at any age," Liggett said.
Common colds and related complications cost an estimated $60 billion a year in direct and indirect costs in the United States, the researchers wrote.
They also believe they may find ways to design drugs to fight the rhinoviruses, which use their single gene to move rapidly from person to person, causing symptoms that range from irritating sniffles to pneumonia.
Instead of designing one drug to cure the common cold, several may be needed because the virus mutates so efficiently, said Dr. Stephen Liggett of the University of Maryland medical school, who led the study published in the journal Science.
"We may end up having four or five drugs," Liggett said in a telephone interview on Thursday.
The hope had been that it might be easy to fight the viruses, which sicken children on average 10 times a year and adults at least twice a year on average.
This is because any rhinovirus has just one gene, which in turn makes a giant protein that appears to do little or nothing until it gets chopped up into 11 smaller pieces by an enzyme called a protease.
Researchers tried to attack this big, clumsy protein before. "The first drug, the virus mutated around it," Liggett said. "But now that we have all the pieces we can begin to understand what areas are not so flexible. We can begin to do some more rational drug design."
For example. it might be possible to attack the protease -- an approach that has worked in fighting AIDS. "If we could inhibit that protease from cleaving that protein, maybe we could render all rhinoviruses ineffective," Liggett said.
Liggett's team also found the viruses take a shortcut in making the proteins, which probably speeds up their ability to make a person feel sick soon after infection.
Claire Fraser-Liggett, who directs the Institute for Genome Sciences and also worked on the study, called this a "new insight."
The viruses also swap genes promiscuously in the equivalent of viral sex, a process known as recombination. This helps them constantly change and adapt.
"We generally think of colds as a nuisance, but they can be debilitating in the very young and in older individuals, and can trigger asthma attacks at any age," Liggett said.
Common colds and related complications cost an estimated $60 billion a year in direct and indirect costs in the United States, the researchers wrote.
Nanoparticle 'Smart Bomb' Targets Drug Delivery to Cancer Cells
Researchers at North Carolina State University have successfully modified a common plant virus to deliver drugs only to specific cells inside the human body, without affecting surrounding tissue.
These tiny "smart bombs" - each one thousands of times smaller than the width of a human hair - could lead to more effective chemotherapy treatments with greatly reduced, or even eliminated, side effects.
Drs. Stefan Franzen, professor of chemistry, and Steven Lommel, professor of plant pathology and genetics, collaborated on the project, utilizing the special properties of a fairly common and non-toxic plant virus as a means to convey drugs to the target cells.
The researchers say that the virus is appealing in both its ability to survive outside of a plant host and its built-in "cargo space" of 17 nanometers, which can be used to carry chemotherapy drugs directly to tumor cells. The researchers deploy the virus by attaching small proteins, called signal peptides, to its exterior that cause the virus to "seek out" particular cells, such as cancer cells. Those same signal peptides serve as "passwords" that allow the virus to enter the cancer cell, where it releases its cargo.
"We had tried a number of different nanoparticles as cell-targeting vectors," Franzen says. "The plant virus is superior in terms of stability, ease of manufacture, ability to target cells and ability to carry therapeutic cargo."
Calcium is the key to keeping the virus' cargo enclosed. When the virus is in the bloodstream, calcium is also abundant. Inside individual cells, however, calcium levels are much lower, which allows the virus to open, delivering the cancer drugs only to the targeted cells.
"Another factor that makes the virus unique is the toughness of its shell," Lommel says. "When the virus is in a closed state, nothing will leak out of the interior, and when it does open, it opens slowly, which means that the virus has time to enter the cell nucleus before deploying its cargo, which increases the drug's efficacy."
The researchers believe that their method will alleviate the side effects of common chemotherapy treatments, while maximizing the effectiveness of the treatment.
These tiny "smart bombs" - each one thousands of times smaller than the width of a human hair - could lead to more effective chemotherapy treatments with greatly reduced, or even eliminated, side effects.
Drs. Stefan Franzen, professor of chemistry, and Steven Lommel, professor of plant pathology and genetics, collaborated on the project, utilizing the special properties of a fairly common and non-toxic plant virus as a means to convey drugs to the target cells.
The researchers say that the virus is appealing in both its ability to survive outside of a plant host and its built-in "cargo space" of 17 nanometers, which can be used to carry chemotherapy drugs directly to tumor cells. The researchers deploy the virus by attaching small proteins, called signal peptides, to its exterior that cause the virus to "seek out" particular cells, such as cancer cells. Those same signal peptides serve as "passwords" that allow the virus to enter the cancer cell, where it releases its cargo.
"We had tried a number of different nanoparticles as cell-targeting vectors," Franzen says. "The plant virus is superior in terms of stability, ease of manufacture, ability to target cells and ability to carry therapeutic cargo."
Calcium is the key to keeping the virus' cargo enclosed. When the virus is in the bloodstream, calcium is also abundant. Inside individual cells, however, calcium levels are much lower, which allows the virus to open, delivering the cancer drugs only to the targeted cells.
"Another factor that makes the virus unique is the toughness of its shell," Lommel says. "When the virus is in a closed state, nothing will leak out of the interior, and when it does open, it opens slowly, which means that the virus has time to enter the cell nucleus before deploying its cargo, which increases the drug's efficacy."
The researchers believe that their method will alleviate the side effects of common chemotherapy treatments, while maximizing the effectiveness of the treatment.
Zoledronic Acid May Help Reduce Breast Cancer Growth
For premenopausal women with early hormone-responsive breast cancer, bisphosphonates during adjuvant endocrine treatment may improve disease-free survival, researchers found.
Action Points
* Explain to interested patients that zoledronic acid is given to breast cancer patients on endocrine therapy to protect bone health.
Note that zoledronic acid has been shown to have potential antitumor activity in preclinical and early phase studies.
The addition of zoledronic acid (Zometa) reduced the risk of disease progression by 36% compared with adjuvant endocrine therapy alone (absolute difference -3.2 percentage points, P=0.01), found Michael Gnant, M.D., of the Medical University of Vienna, and colleagues.
While the randomized trial showed no mortality benefit, toxicity was minimal, they reported in the Feb. 12 issue of the New England Journal of Medicine.
The results confirm the initial report of the data at last year's American Society of Clinical Oncology meeting.
This effect was comparable to the absolute advantage in disease-free survival seen in prior trials for aromatase inhibitors versus tamoxifen among postmenopausal women with early breast cancer, the researchers noted.
Given the similar advantage of aromatase inhibitors in one prior study of premenopausal women, their Austrian Breast and Colorectal Cancer Study Group trial was also designed to compare endocrine treatments.
The study included 1,803 premenopausal women with endocrine-responsive stage I or II breast cancer who were given the gonadotropin-releasing hormone analog goserelin (Zoladex, 3.6 mg subcutaneously every 28 days) after primary surgery.
They were randomized to adjuvant treatment with tamoxifen (20 mg per day given orally) or anastrozole (Arimidex) at 1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every six months) for three years.
However, unexpectedly, anastrozole did not improve outcomes among premenopausal women in the study at a median follow-up of 47.8 months. The findings compared with tamoxifen included:
* No effect on disease-free survival (hazard ratio 1.10, P=0.59)
* No impact on recurrence-free survival (HR 1.11, P=0.53)
* No advantage for overall mortality (HR 1.80, P=0.70)
The difference compared with postmenopausal women might have been "because of the dominant effect of ovarian suppression on estrogen levels in premenopausal women," the researchers suggested. "Moreover, long-term administration of goserelin can reduce androgen levels, thereby limiting the available substrate for aromatase activity."
Other findings for the addition of zoledronic acid compared with endocrine therapy alone included:
* Improved disease-free survival rates (94.0% versus 90.8%, P=0.01)
* A 36% relative reduction in risk of disease progression (P=0.01)
* Improved recurrence-free survival at 47.8 months (94.0% versus 90.9%, P=0.01)
* A 35% reduction in risk of recurrence (P=0.02)
* No difference in risk of death (HR 0.60, P=0.11).
* No significant effect on survival free of bone metastasis despite a 32% risk reduction (HR 0.68, P=0.22), which the researchers attributed to a small number of events
The number needed to treat with zoledronic acid to prevent disease progression in one patient was 31 in the study, "consistent with the number needed to treat for cancer therapies that in the past have caused a shift in treatment standards," such as docetaxel (Taxotere) and paclitaxel (Taxol), Dr. Gnant's group noted.
The researchers noted no excess toxicity aside from "known drug-safety profiles." Zoledronic acid-treated patients had slightly higher incidences of bone pain (35% versus 25%), arthralgia (24% versus 18%), and fever (9% versus 2%), with apparently additive effects for the bone-related adverse events.
Three suspected cases of osteonecrosis of the jaw among zoledronic acid-treated patients were all ruled out after review of dental records. There were also no signs of renal toxicity.
The effect on breast cancer may be explained by preclinical and early phase studies that showed zoledronic acid inhibited tumor-cell adhesion, invasion, and proliferation and induced tumor cell apoptosis, acted synergistically with chemotherapy agents, and exerted antiangiogenic effects, Dr. Gnant's group said.
Action Points
* Explain to interested patients that zoledronic acid is given to breast cancer patients on endocrine therapy to protect bone health.
Note that zoledronic acid has been shown to have potential antitumor activity in preclinical and early phase studies.
The addition of zoledronic acid (Zometa) reduced the risk of disease progression by 36% compared with adjuvant endocrine therapy alone (absolute difference -3.2 percentage points, P=0.01), found Michael Gnant, M.D., of the Medical University of Vienna, and colleagues.
While the randomized trial showed no mortality benefit, toxicity was minimal, they reported in the Feb. 12 issue of the New England Journal of Medicine.
The results confirm the initial report of the data at last year's American Society of Clinical Oncology meeting.
This effect was comparable to the absolute advantage in disease-free survival seen in prior trials for aromatase inhibitors versus tamoxifen among postmenopausal women with early breast cancer, the researchers noted.
Given the similar advantage of aromatase inhibitors in one prior study of premenopausal women, their Austrian Breast and Colorectal Cancer Study Group trial was also designed to compare endocrine treatments.
The study included 1,803 premenopausal women with endocrine-responsive stage I or II breast cancer who were given the gonadotropin-releasing hormone analog goserelin (Zoladex, 3.6 mg subcutaneously every 28 days) after primary surgery.
They were randomized to adjuvant treatment with tamoxifen (20 mg per day given orally) or anastrozole (Arimidex) at 1 mg per day given orally) with or without zoledronic acid (4 mg given intravenously every six months) for three years.
However, unexpectedly, anastrozole did not improve outcomes among premenopausal women in the study at a median follow-up of 47.8 months. The findings compared with tamoxifen included:
* No effect on disease-free survival (hazard ratio 1.10, P=0.59)
* No impact on recurrence-free survival (HR 1.11, P=0.53)
* No advantage for overall mortality (HR 1.80, P=0.70)
The difference compared with postmenopausal women might have been "because of the dominant effect of ovarian suppression on estrogen levels in premenopausal women," the researchers suggested. "Moreover, long-term administration of goserelin can reduce androgen levels, thereby limiting the available substrate for aromatase activity."
Other findings for the addition of zoledronic acid compared with endocrine therapy alone included:
* Improved disease-free survival rates (94.0% versus 90.8%, P=0.01)
* A 36% relative reduction in risk of disease progression (P=0.01)
* Improved recurrence-free survival at 47.8 months (94.0% versus 90.9%, P=0.01)
* A 35% reduction in risk of recurrence (P=0.02)
* No difference in risk of death (HR 0.60, P=0.11).
* No significant effect on survival free of bone metastasis despite a 32% risk reduction (HR 0.68, P=0.22), which the researchers attributed to a small number of events
The number needed to treat with zoledronic acid to prevent disease progression in one patient was 31 in the study, "consistent with the number needed to treat for cancer therapies that in the past have caused a shift in treatment standards," such as docetaxel (Taxotere) and paclitaxel (Taxol), Dr. Gnant's group noted.
The researchers noted no excess toxicity aside from "known drug-safety profiles." Zoledronic acid-treated patients had slightly higher incidences of bone pain (35% versus 25%), arthralgia (24% versus 18%), and fever (9% versus 2%), with apparently additive effects for the bone-related adverse events.
Three suspected cases of osteonecrosis of the jaw among zoledronic acid-treated patients were all ruled out after review of dental records. There were also no signs of renal toxicity.
The effect on breast cancer may be explained by preclinical and early phase studies that showed zoledronic acid inhibited tumor-cell adhesion, invasion, and proliferation and induced tumor cell apoptosis, acted synergistically with chemotherapy agents, and exerted antiangiogenic effects, Dr. Gnant's group said.
February 11, 2009
Circulating Tumor Cells Could Predict Prostate Cancer Outcome
Checking for changes in the number of circulating tumor cells (CTCs) could help doctors predict advanced prostate cancer patients' survival and response to treatment, U.S. researchers report.
They studied the association between CTC numbers (before and after treatment) and survival, along with other factors such as changes in levels of prostate-specific antigen (PSA) and baseline lactate dehydrogenase (LDH) in 164 prostate cancer patients starting first-line chemotherapy regimens.
High values of CTC numbers and PSA levels before treatment were associated with increased risk of death. At four, eight and 12 weeks after treatment, changes in CTC numbers were strongly associated with increased risk of death, while changes in PSA were only marginally associated with increased risk of death.
The findings confirm that pre-treatment CTC numbers help predict survival of prostate cancer patients starting first-line chemotherapy. CTC numbers also help monitor disease status and response to treatment, and CTC is a better predictor than PSA, the researchers said.
"CTC number[s] ... can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials," wrote study author Howard Sher, of Memorial Sloan-Kettering Cancer Center in New York City. "Use as an intermediate or surrogate endpoint for survival could shorten the time line for drug approval," although "several prospective trials are needed to generate evidence to guide the use of biomarkers."
The study was published online and will appear in the March print issue of The Lancet Oncology.
More information
The American Cancer Society has more about prostate cancer.
They studied the association between CTC numbers (before and after treatment) and survival, along with other factors such as changes in levels of prostate-specific antigen (PSA) and baseline lactate dehydrogenase (LDH) in 164 prostate cancer patients starting first-line chemotherapy regimens.
High values of CTC numbers and PSA levels before treatment were associated with increased risk of death. At four, eight and 12 weeks after treatment, changes in CTC numbers were strongly associated with increased risk of death, while changes in PSA were only marginally associated with increased risk of death.
The findings confirm that pre-treatment CTC numbers help predict survival of prostate cancer patients starting first-line chemotherapy. CTC numbers also help monitor disease status and response to treatment, and CTC is a better predictor than PSA, the researchers said.
"CTC number[s] ... can be used to monitor disease status and might be useful as an intermediate endpoint of survival in clinical trials," wrote study author Howard Sher, of Memorial Sloan-Kettering Cancer Center in New York City. "Use as an intermediate or surrogate endpoint for survival could shorten the time line for drug approval," although "several prospective trials are needed to generate evidence to guide the use of biomarkers."
The study was published online and will appear in the March print issue of The Lancet Oncology.
More information
The American Cancer Society has more about prostate cancer.
Subscribe to:
Posts (Atom)