More than 75% of adults with sickle cell anemia who have frequent pain crises fail to receive hydroxyurea therapy as strongly recommended in National Heart, Lung, and Blood Institute clinical guidelines, according to a Research Letter to the Editor published online April 28 in JAMA.

Despite proven benefits in decreasing pain crises, hospitalizations, blood transfusions, and possibly mortality, hydroxyurea, a “safe and inexpensive drug,” is thought to be underused. To document the actual use of the drug when indicated, investigators analyzed information in a nationwide insurance claims database covering nearly 27 million patients per year. They focused on the records of 570 adults hospitalized or treated in an emergency department for a sickle cell pain crisis at least three times during a 1-year period, said Dr. Nicolas Stettler of the Lewin Group, a health care consulting firm in Falls Church, Va., and his associates.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

Only 15.1% of these patients received hydroxyurea within 3 months of their third crisis, only 18.2% received the agent within 6 months, and only 22.7% received it within 12 months. These figures likely represent a conservative estimate of the hydroxyurea treatment gap, since the study didn’t include the large uninsured and publicly insured populations who have more limited access to health care, Dr. Stettler and his associates noted (JAMA 2015;313:1671-2).

Several barriers to this treatment have been identified in previous research, including fear of adverse events, lack of clinician training, and failure to use shared decision making. “To address this gap, it may be necessary to enhance patient outreach and clinician training and develop health care quality measures aimed at increasing the use of hydroxyurea for all patients who would benefit,” they added.

More than 75% of adults with sickle cell anemia who have frequent pain crises fail to receive hydroxyurea therapy as strongly recommended in National Heart, Lung, and Blood Institute clinical guidelines, according to a Research Letter to the Editor published online April 28 in JAMA.

Despite proven benefits in decreasing pain crises, hospitalizations, blood transfusions, and possibly mortality, hydroxyurea, a “safe and inexpensive drug,” is thought to be underused. To document the actual use of the drug when indicated, investigators analyzed information in a nationwide insurance claims database covering nearly 27 million patients per year. They focused on the records of 570 adults hospitalized or treated in an emergency department for a sickle cell pain crisis at least three times during a 1-year period, said Dr. Nicolas Stettler of the Lewin Group, a health care consulting firm in Falls Church, Va., and his associates.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

Only 15.1% of these patients received hydroxyurea within 3 months of their third crisis, only 18.2% received the agent within 6 months, and only 22.7% received it within 12 months. These figures likely represent a conservative estimate of the hydroxyurea treatment gap, since the study didn’t include the large uninsured and publicly insured populations who have more limited access to health care, Dr. Stettler and his associates noted (JAMA 2015;313:1671-2).

Several barriers to this treatment have been identified in previous research, including fear of adverse events, lack of clinician training, and failure to use shared decision making. “To address this gap, it may be necessary to enhance patient outreach and clinician training and develop health care quality measures aimed at increasing the use of hydroxyurea for all patients who would benefit,” they added.

More than 75% of adults with sickle cell anemia who have frequent pain crises fail to receive hydroxyurea therapy as strongly recommended in National Heart, Lung, and Blood Institute clinical guidelines, according to a Research Letter to the Editor published online April 28 in JAMA.

Despite proven benefits in decreasing pain crises, hospitalizations, blood transfusions, and possibly mortality, hydroxyurea, a “safe and inexpensive drug,” is thought to be underused. To document the actual use of the drug when indicated, investigators analyzed information in a nationwide insurance claims database covering nearly 27 million patients per year. They focused on the records of 570 adults hospitalized or treated in an emergency department for a sickle cell pain crisis at least three times during a 1-year period, said Dr. Nicolas Stettler of the Lewin Group, a health care consulting firm in Falls Church, Va., and his associates.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

Only 15.1% of these patients received hydroxyurea within 3 months of their third crisis, only 18.2% received the agent within 6 months, and only 22.7% received it within 12 months. These figures likely represent a conservative estimate of the hydroxyurea treatment gap, since the study didn’t include the large uninsured and publicly insured populations who have more limited access to health care, Dr. Stettler and his associates noted (JAMA 2015;313:1671-2).

Several barriers to this treatment have been identified in previous research, including fear of adverse events, lack of clinician training, and failure to use shared decision making. “To address this gap, it may be necessary to enhance patient outreach and clinician training and develop health care quality measures aimed at increasing the use of hydroxyurea for all patients who would benefit,” they added.

Participating in a short series of phone conversations with trained counselors can substantially boost recovery and reduce pain in patients after spinal surgery, according to a study published online ahead of print March 28 in Archives of Physical Medicine and Rehabilitation.

The phone calls were designed to enhance standard pre- and post-operative care by reinforcing the value of continuing with physical therapy and back-strengthening exercise regimens.

“Phone counseling appears to be an easy, low-cost strategy that yields meaningful results by improving patient engagement in physical therapy and at-home exercise programs that are so vital for their recovery,” said lead study author Richard Skolasky Jr., ScD, Associate Professor of Orthopedic Surgery at the Johns Hopkins University School of Medicine in Baltimore.

The study included 122 patients ages 46 to 72, who underwent surgery at Johns Hopkins University between 2009 and 2012 to correct spinal stenosis. Each patient was assigned either home exercise programs or physical therapy to help accelerate their recovery time. About half of the patients also received a series of phone counseling sessions from a trained spinal surgery counselor to discuss the importance of exercise in their recovery. The first and most detailed phone session took place a few weeks before the patients had their surgeries. Two follow-up sessions occurred at 6 weeks and at 3 months after the operation was performed.

The study found that patients who received phone calls participated in physical therapy and home exercise at higher rates, and had less pain and less disability 6 months after their surgery, compared with the standard-approach group. Six months after surgery, 74% of patients who received phone counseling experienced significant improvements on standard measures of physical functioning and self-reported measures of pain, compared with 41% of people who did not receive phone calls.

“Modern orthopedic science has made great strides in surgical techniques to correct spinal deformities and achieved significant progress in developing physical therapies that boost the benefits of surgery, but we have not been all that good at motivating and engaging patients to partake in such post-surgical recovery programs,” said co-investigator Stephen Wegener, PhD, Associate Professor of Physical Medicine and Rehabilitation at Johns Hopkins University.

“The findings of our research suggest we may have found a way to add that missing ingredient that draws patients to be more active participants in their physical rehabilitation and recovery,” stated Dr. Wegener.

Participating in a short series of phone conversations with trained counselors can substantially boost recovery and reduce pain in patients after spinal surgery, according to a study published online ahead of print March 28 in Archives of Physical Medicine and Rehabilitation.

The phone calls were designed to enhance standard pre- and post-operative care by reinforcing the value of continuing with physical therapy and back-strengthening exercise regimens.

“Phone counseling appears to be an easy, low-cost strategy that yields meaningful results by improving patient engagement in physical therapy and at-home exercise programs that are so vital for their recovery,” said lead study author Richard Skolasky Jr., ScD, Associate Professor of Orthopedic Surgery at the Johns Hopkins University School of Medicine in Baltimore.

The study included 122 patients ages 46 to 72, who underwent surgery at Johns Hopkins University between 2009 and 2012 to correct spinal stenosis. Each patient was assigned either home exercise programs or physical therapy to help accelerate their recovery time. About half of the patients also received a series of phone counseling sessions from a trained spinal surgery counselor to discuss the importance of exercise in their recovery. The first and most detailed phone session took place a few weeks before the patients had their surgeries. Two follow-up sessions occurred at 6 weeks and at 3 months after the operation was performed.

The study found that patients who received phone calls participated in physical therapy and home exercise at higher rates, and had less pain and less disability 6 months after their surgery, compared with the standard-approach group. Six months after surgery, 74% of patients who received phone counseling experienced significant improvements on standard measures of physical functioning and self-reported measures of pain, compared with 41% of people who did not receive phone calls.

“Modern orthopedic science has made great strides in surgical techniques to correct spinal deformities and achieved significant progress in developing physical therapies that boost the benefits of surgery, but we have not been all that good at motivating and engaging patients to partake in such post-surgical recovery programs,” said co-investigator Stephen Wegener, PhD, Associate Professor of Physical Medicine and Rehabilitation at Johns Hopkins University.

“The findings of our research suggest we may have found a way to add that missing ingredient that draws patients to be more active participants in their physical rehabilitation and recovery,” stated Dr. Wegener.

Participating in a short series of phone conversations with trained counselors can substantially boost recovery and reduce pain in patients after spinal surgery, according to a study published online ahead of print March 28 in Archives of Physical Medicine and Rehabilitation.

The phone calls were designed to enhance standard pre- and post-operative care by reinforcing the value of continuing with physical therapy and back-strengthening exercise regimens.

“Phone counseling appears to be an easy, low-cost strategy that yields meaningful results by improving patient engagement in physical therapy and at-home exercise programs that are so vital for their recovery,” said lead study author Richard Skolasky Jr., ScD, Associate Professor of Orthopedic Surgery at the Johns Hopkins University School of Medicine in Baltimore.

The study included 122 patients ages 46 to 72, who underwent surgery at Johns Hopkins University between 2009 and 2012 to correct spinal stenosis. Each patient was assigned either home exercise programs or physical therapy to help accelerate their recovery time. About half of the patients also received a series of phone counseling sessions from a trained spinal surgery counselor to discuss the importance of exercise in their recovery. The first and most detailed phone session took place a few weeks before the patients had their surgeries. Two follow-up sessions occurred at 6 weeks and at 3 months after the operation was performed.

The study found that patients who received phone calls participated in physical therapy and home exercise at higher rates, and had less pain and less disability 6 months after their surgery, compared with the standard-approach group. Six months after surgery, 74% of patients who received phone counseling experienced significant improvements on standard measures of physical functioning and self-reported measures of pain, compared with 41% of people who did not receive phone calls.

“Modern orthopedic science has made great strides in surgical techniques to correct spinal deformities and achieved significant progress in developing physical therapies that boost the benefits of surgery, but we have not been all that good at motivating and engaging patients to partake in such post-surgical recovery programs,” said co-investigator Stephen Wegener, PhD, Associate Professor of Physical Medicine and Rehabilitation at Johns Hopkins University.

“The findings of our research suggest we may have found a way to add that missing ingredient that draws patients to be more active participants in their physical rehabilitation and recovery,” stated Dr. Wegener.

Inside the Pennsylvania

Convention Center, site of the

AACR Annual Meeting 2015

PHILADELPHIA—When current treatment approaches failed to save a young patient with non-Hodgkin lymphoma (NHL), a researcher from The Children’s Hospital of Philadelphia was driven to investigate new therapeutic options.

The investigation led the researcher, Mala Talekar, MBBS, to ONC201 (formerly TIC10), a small molecule that induces apoptosis by increasing surface expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Preclinical experiments showed that ONC201 is active against NHL as a single agent, and it synergizes with chemotherapeutic drugs that are already used to treat NHL.

Dr Talekar and her colleagues described these experiments in a poster presented at the AACR Annual Meeting 2015 (abstract 5387). Some of the investigators involved in this research are employed by Oncoceutics, Inc., the company developing ONC201.

A researcher’s inspiration

“When I was doing my fellowship training, I had a teenage boy who had a rare form of non-Hodgkin’s lymphoma,” Dr Talekar explained. “He did not survive, despite receiving multiple treatments that are available for pediatric non-Hodgkin’s lymphoma.”

The boy’s death inspired Dr Talekar to seek new and better approaches to treat NHL. A search of the medical literature unearthed several articles detailing a TRAIL-based approach to treating lymphoma. So she decided to further investigate the effects of TRAIL in NHL.

“I first tried TRAIL in one lymphoma cell line,” she said. “And even though it did kill the cancer cells, it did not really give a satisfactory response.”

So Dr Talekar turned to the TRAIL agonist antibodies lexatumumab and mapatumumab, introducing each of them to human lymphoma cells. Although the antibodies caused more cell death than TRAIL itself, the response was still not satisfactory, she said.

“Fortunately for me, while I was working in the lab, one of the postdocs, Joshua Allen, discovered a new molecule called TRAIL-inducing compound 10, or TIC10,” Dr Talekar said. “So I tried TIC10—it is now called ONC201—and it gave a beautiful dose-response curve, causing complete cell death of the lymphoma cells.”

Dr Talekar was “very inspired” by this result and decided to test ONC201 in 8 different NHL cell lines—4 Burkitt lymphoma (Daudi, Raji, Ramos, and BJAB), 1 anaplastic large-cell lymphoma (Karpas299), and 3 mantle cell lymphoma (UPN2, Granta, and NCEB) cell lines.

“I found a beautiful dose-response curve,” Dr Talekar said, “suggesting that this molecule works in micromolar concentrations across all of the lymphoma cell lines.”

Elucidating the mechanism

Dr Talekar then set out to determine exactly how ONC201 causes cell death in NHL. Flow cytometry revealed that, as the dose of ONC201 increases, cell death increases, as does sub-G1 DNA content. This suggests the drug is causing cell death by apoptosis.

Next, Dr Talekar introduced ONC201 to NHL cell lines along with a pan-caspase inhibitor. She found the inhibitor blocked ONC201-induced apoptosis, which suggests ONC201 works via the caspase-mediated apoptotic pathway.

“The initial mechanism of action proposed for ONC201 was dual inactivation of two kinases, Akt and ERK,” Dr Talekar noted. “The dual inactivation causes dephosphorylation of Foxo3a. This causes its translocation to the nucleus and downstream upregulation of TRAIL, and, therefore, increased surface TRAIL expression. And we know increases in surface TRAIL cause cell death by apoptosis.”

With this in mind, Dr Talekar looked for increases in surface TRIAL after she incubated lymphoma cells with ONC201. She observed a dose-dependent increase in surface TRAIL and a linear correlation between the increase in TRAIL and apoptosis.

Then, she introduced ONC201 and a TRAIL-sequestering antibody, RIK-2, to lymphoma cells. RIK-2 inhibited apoptosis, which suggests ONC201 works as an anti-apoptotic agent via the TRAIL pathway.

Further testing

As a final step, Dr Talekar tested ONC201 in combination with chemotherapy drugs that are already used to treat pediatric NHL. She observed at least an additive effect, and sometimes a synergistic effect, between the drugs. The best responses occurred when she combined ONC201 with cytarabine, bortezomib, or doxorubicin.

Now, Dr Talekar is working on testing ONC201 in combination with cytarabine in a xenograft model of Burkitt lymphoma.

She noted that other in vivo research has suggested ONC201 has a “very benign safety profile.” In another poster presented at AACR 2015 (abstract 4479), researchers reported results indicating that ONC201 is safe.

“They have tested it in mice and dogs and found that, at 10-fold the therapeutic dose, you don’t see much toxicity at all,” Dr Talekar said.

ONC201 is also being tested in a phase 1 study of adults with advanced solid tumors. Phase 1 studies of the drug in relapsed or refractory NHL and relapsed or refractory acute leukemias and high-risk myelodysplastic syndromes are not yet recruiting patients.

Inside the Pennsylvania

Convention Center, site of the

AACR Annual Meeting 2015

PHILADELPHIA—When current treatment approaches failed to save a young patient with non-Hodgkin lymphoma (NHL), a researcher from The Children’s Hospital of Philadelphia was driven to investigate new therapeutic options.

The investigation led the researcher, Mala Talekar, MBBS, to ONC201 (formerly TIC10), a small molecule that induces apoptosis by increasing surface expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Preclinical experiments showed that ONC201 is active against NHL as a single agent, and it synergizes with chemotherapeutic drugs that are already used to treat NHL.

Dr Talekar and her colleagues described these experiments in a poster presented at the AACR Annual Meeting 2015 (abstract 5387). Some of the investigators involved in this research are employed by Oncoceutics, Inc., the company developing ONC201.

A researcher’s inspiration

“When I was doing my fellowship training, I had a teenage boy who had a rare form of non-Hodgkin’s lymphoma,” Dr Talekar explained. “He did not survive, despite receiving multiple treatments that are available for pediatric non-Hodgkin’s lymphoma.”

The boy’s death inspired Dr Talekar to seek new and better approaches to treat NHL. A search of the medical literature unearthed several articles detailing a TRAIL-based approach to treating lymphoma. So she decided to further investigate the effects of TRAIL in NHL.

“I first tried TRAIL in one lymphoma cell line,” she said. “And even though it did kill the cancer cells, it did not really give a satisfactory response.”

So Dr Talekar turned to the TRAIL agonist antibodies lexatumumab and mapatumumab, introducing each of them to human lymphoma cells. Although the antibodies caused more cell death than TRAIL itself, the response was still not satisfactory, she said.

“Fortunately for me, while I was working in the lab, one of the postdocs, Joshua Allen, discovered a new molecule called TRAIL-inducing compound 10, or TIC10,” Dr Talekar said. “So I tried TIC10—it is now called ONC201—and it gave a beautiful dose-response curve, causing complete cell death of the lymphoma cells.”

Dr Talekar was “very inspired” by this result and decided to test ONC201 in 8 different NHL cell lines—4 Burkitt lymphoma (Daudi, Raji, Ramos, and BJAB), 1 anaplastic large-cell lymphoma (Karpas299), and 3 mantle cell lymphoma (UPN2, Granta, and NCEB) cell lines.

“I found a beautiful dose-response curve,” Dr Talekar said, “suggesting that this molecule works in micromolar concentrations across all of the lymphoma cell lines.”

Elucidating the mechanism

Dr Talekar then set out to determine exactly how ONC201 causes cell death in NHL. Flow cytometry revealed that, as the dose of ONC201 increases, cell death increases, as does sub-G1 DNA content. This suggests the drug is causing cell death by apoptosis.

Next, Dr Talekar introduced ONC201 to NHL cell lines along with a pan-caspase inhibitor. She found the inhibitor blocked ONC201-induced apoptosis, which suggests ONC201 works via the caspase-mediated apoptotic pathway.

“The initial mechanism of action proposed for ONC201 was dual inactivation of two kinases, Akt and ERK,” Dr Talekar noted. “The dual inactivation causes dephosphorylation of Foxo3a. This causes its translocation to the nucleus and downstream upregulation of TRAIL, and, therefore, increased surface TRAIL expression. And we know increases in surface TRAIL cause cell death by apoptosis.”

With this in mind, Dr Talekar looked for increases in surface TRIAL after she incubated lymphoma cells with ONC201. She observed a dose-dependent increase in surface TRAIL and a linear correlation between the increase in TRAIL and apoptosis.

Then, she introduced ONC201 and a TRAIL-sequestering antibody, RIK-2, to lymphoma cells. RIK-2 inhibited apoptosis, which suggests ONC201 works as an anti-apoptotic agent via the TRAIL pathway.

Further testing

As a final step, Dr Talekar tested ONC201 in combination with chemotherapy drugs that are already used to treat pediatric NHL. She observed at least an additive effect, and sometimes a synergistic effect, between the drugs. The best responses occurred when she combined ONC201 with cytarabine, bortezomib, or doxorubicin.

Now, Dr Talekar is working on testing ONC201 in combination with cytarabine in a xenograft model of Burkitt lymphoma.

She noted that other in vivo research has suggested ONC201 has a “very benign safety profile.” In another poster presented at AACR 2015 (abstract 4479), researchers reported results indicating that ONC201 is safe.

“They have tested it in mice and dogs and found that, at 10-fold the therapeutic dose, you don’t see much toxicity at all,” Dr Talekar said.

ONC201 is also being tested in a phase 1 study of adults with advanced solid tumors. Phase 1 studies of the drug in relapsed or refractory NHL and relapsed or refractory acute leukemias and high-risk myelodysplastic syndromes are not yet recruiting patients.

Inside the Pennsylvania

Convention Center, site of the

AACR Annual Meeting 2015

PHILADELPHIA—When current treatment approaches failed to save a young patient with non-Hodgkin lymphoma (NHL), a researcher from The Children’s Hospital of Philadelphia was driven to investigate new therapeutic options.

The investigation led the researcher, Mala Talekar, MBBS, to ONC201 (formerly TIC10), a small molecule that induces apoptosis by increasing surface expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

Preclinical experiments showed that ONC201 is active against NHL as a single agent, and it synergizes with chemotherapeutic drugs that are already used to treat NHL.

Dr Talekar and her colleagues described these experiments in a poster presented at the AACR Annual Meeting 2015 (abstract 5387). Some of the investigators involved in this research are employed by Oncoceutics, Inc., the company developing ONC201.

A researcher’s inspiration

“When I was doing my fellowship training, I had a teenage boy who had a rare form of non-Hodgkin’s lymphoma,” Dr Talekar explained. “He did not survive, despite receiving multiple treatments that are available for pediatric non-Hodgkin’s lymphoma.”

The boy’s death inspired Dr Talekar to seek new and better approaches to treat NHL. A search of the medical literature unearthed several articles detailing a TRAIL-based approach to treating lymphoma. So she decided to further investigate the effects of TRAIL in NHL.

“I first tried TRAIL in one lymphoma cell line,” she said. “And even though it did kill the cancer cells, it did not really give a satisfactory response.”

So Dr Talekar turned to the TRAIL agonist antibodies lexatumumab and mapatumumab, introducing each of them to human lymphoma cells. Although the antibodies caused more cell death than TRAIL itself, the response was still not satisfactory, she said.

“Fortunately for me, while I was working in the lab, one of the postdocs, Joshua Allen, discovered a new molecule called TRAIL-inducing compound 10, or TIC10,” Dr Talekar said. “So I tried TIC10—it is now called ONC201—and it gave a beautiful dose-response curve, causing complete cell death of the lymphoma cells.”

Dr Talekar was “very inspired” by this result and decided to test ONC201 in 8 different NHL cell lines—4 Burkitt lymphoma (Daudi, Raji, Ramos, and BJAB), 1 anaplastic large-cell lymphoma (Karpas299), and 3 mantle cell lymphoma (UPN2, Granta, and NCEB) cell lines.

“I found a beautiful dose-response curve,” Dr Talekar said, “suggesting that this molecule works in micromolar concentrations across all of the lymphoma cell lines.”

Elucidating the mechanism

Dr Talekar then set out to determine exactly how ONC201 causes cell death in NHL. Flow cytometry revealed that, as the dose of ONC201 increases, cell death increases, as does sub-G1 DNA content. This suggests the drug is causing cell death by apoptosis.

Next, Dr Talekar introduced ONC201 to NHL cell lines along with a pan-caspase inhibitor. She found the inhibitor blocked ONC201-induced apoptosis, which suggests ONC201 works via the caspase-mediated apoptotic pathway.

“The initial mechanism of action proposed for ONC201 was dual inactivation of two kinases, Akt and ERK,” Dr Talekar noted. “The dual inactivation causes dephosphorylation of Foxo3a. This causes its translocation to the nucleus and downstream upregulation of TRAIL, and, therefore, increased surface TRAIL expression. And we know increases in surface TRAIL cause cell death by apoptosis.”

With this in mind, Dr Talekar looked for increases in surface TRIAL after she incubated lymphoma cells with ONC201. She observed a dose-dependent increase in surface TRAIL and a linear correlation between the increase in TRAIL and apoptosis.

Then, she introduced ONC201 and a TRAIL-sequestering antibody, RIK-2, to lymphoma cells. RIK-2 inhibited apoptosis, which suggests ONC201 works as an anti-apoptotic agent via the TRAIL pathway.

Further testing

As a final step, Dr Talekar tested ONC201 in combination with chemotherapy drugs that are already used to treat pediatric NHL. She observed at least an additive effect, and sometimes a synergistic effect, between the drugs. The best responses occurred when she combined ONC201 with cytarabine, bortezomib, or doxorubicin.

Now, Dr Talekar is working on testing ONC201 in combination with cytarabine in a xenograft model of Burkitt lymphoma.

She noted that other in vivo research has suggested ONC201 has a “very benign safety profile.” In another poster presented at AACR 2015 (abstract 4479), researchers reported results indicating that ONC201 is safe.

“They have tested it in mice and dogs and found that, at 10-fold the therapeutic dose, you don’t see much toxicity at all,” Dr Talekar said.

ONC201 is also being tested in a phase 1 study of adults with advanced solid tumors. Phase 1 studies of the drug in relapsed or refractory NHL and relapsed or refractory acute leukemias and high-risk myelodysplastic syndromes are not yet recruiting patients.

DNA methylation

Image by Christoph Bock

A new study helps explain how the anticancer drug decitabine reverses cell damage and has revealed a potential biomarker that could indicate a

patient’s cancer stage and response to treatment.

Investigators found that decitabine combats some of cancer’s effects by taking the place of the nucleotide cytosine at specific locations on a replicating DNA strand.

In mimicking cytosine, the drug helps “tame” cancerous cells by turning on tumor suppressors and turning off oncogenes.

The investigators also found that decitabine causes an unexpected boost in the amount of a molecule known as 5-hydroxymethylcytosine (5hmC). Because many types of cancer cause 5hmC levels to plummet, an uptick in 5hmC could be a sign that cancer treatments are working.

“We think that the expression of 5hmC could be used as a biomarker to define the stage or the aggressiveness of cancer and to possibly indicate the effectiveness of cancer treatment,” said Joseph Irudayaraj, PhD, of Purdue University in West Lafayette, Indiana. “This could help us monitor the clinical success of patients receiving decitabine.”

Dr Irudayaraj and his colleagues reported these findings in Nature Scientific Reports.

Decitabine, one of the first epigenetic drugs, helps reverse the altered methylation patterns in cancerous cells, but its precise mode of action has not been clear.

Using a combination of models, Dr Irudayaraj and his colleagues showed that decitabine is taking the place of cytosine at strategic positions on replicating strands of DNA in cancer cells.

When an enzyme tries to add a methyl group to silence decitabine, the drug traps it in place, preventing methylation. This triggers another group of enzymes to transform a methylated cytosine on the parent DNA strand into 5hmC, a molecule whose biological function is not yet known.

The investigators confirmed the increase in 5hmC levels in decitabine-treated leukemia cells.

To better explain the team’s findings, Basudev Chowdhury, PhD, also of Purdue University, likened decitabine to a text editor that restores meaning to a garbled sentence and compared conventional chemotherapy to a delete button.

“Think of nucleotides as the alphabet with which our cells compose messages,” he said. “Epigenetics helps translate those messages into actions such as the production of proteins. But cancer can jumble the messages, making them nonsensical. Decitabine helps revise the messages so they can be understood.”

DNA methylation

Image by Christoph Bock

A new study helps explain how the anticancer drug decitabine reverses cell damage and has revealed a potential biomarker that could indicate a

patient’s cancer stage and response to treatment.

Investigators found that decitabine combats some of cancer’s effects by taking the place of the nucleotide cytosine at specific locations on a replicating DNA strand.

In mimicking cytosine, the drug helps “tame” cancerous cells by turning on tumor suppressors and turning off oncogenes.

The investigators also found that decitabine causes an unexpected boost in the amount of a molecule known as 5-hydroxymethylcytosine (5hmC). Because many types of cancer cause 5hmC levels to plummet, an uptick in 5hmC could be a sign that cancer treatments are working.

“We think that the expression of 5hmC could be used as a biomarker to define the stage or the aggressiveness of cancer and to possibly indicate the effectiveness of cancer treatment,” said Joseph Irudayaraj, PhD, of Purdue University in West Lafayette, Indiana. “This could help us monitor the clinical success of patients receiving decitabine.”

Dr Irudayaraj and his colleagues reported these findings in Nature Scientific Reports.

Decitabine, one of the first epigenetic drugs, helps reverse the altered methylation patterns in cancerous cells, but its precise mode of action has not been clear.

Using a combination of models, Dr Irudayaraj and his colleagues showed that decitabine is taking the place of cytosine at strategic positions on replicating strands of DNA in cancer cells.

When an enzyme tries to add a methyl group to silence decitabine, the drug traps it in place, preventing methylation. This triggers another group of enzymes to transform a methylated cytosine on the parent DNA strand into 5hmC, a molecule whose biological function is not yet known.

The investigators confirmed the increase in 5hmC levels in decitabine-treated leukemia cells.

To better explain the team’s findings, Basudev Chowdhury, PhD, also of Purdue University, likened decitabine to a text editor that restores meaning to a garbled sentence and compared conventional chemotherapy to a delete button.

“Think of nucleotides as the alphabet with which our cells compose messages,” he said. “Epigenetics helps translate those messages into actions such as the production of proteins. But cancer can jumble the messages, making them nonsensical. Decitabine helps revise the messages so they can be understood.”

DNA methylation

Image by Christoph Bock

A new study helps explain how the anticancer drug decitabine reverses cell damage and has revealed a potential biomarker that could indicate a

patient’s cancer stage and response to treatment.

Investigators found that decitabine combats some of cancer’s effects by taking the place of the nucleotide cytosine at specific locations on a replicating DNA strand.

In mimicking cytosine, the drug helps “tame” cancerous cells by turning on tumor suppressors and turning off oncogenes.

The investigators also found that decitabine causes an unexpected boost in the amount of a molecule known as 5-hydroxymethylcytosine (5hmC). Because many types of cancer cause 5hmC levels to plummet, an uptick in 5hmC could be a sign that cancer treatments are working.

“We think that the expression of 5hmC could be used as a biomarker to define the stage or the aggressiveness of cancer and to possibly indicate the effectiveness of cancer treatment,” said Joseph Irudayaraj, PhD, of Purdue University in West Lafayette, Indiana. “This could help us monitor the clinical success of patients receiving decitabine.”

Dr Irudayaraj and his colleagues reported these findings in Nature Scientific Reports.

Decitabine, one of the first epigenetic drugs, helps reverse the altered methylation patterns in cancerous cells, but its precise mode of action has not been clear.

Using a combination of models, Dr Irudayaraj and his colleagues showed that decitabine is taking the place of cytosine at strategic positions on replicating strands of DNA in cancer cells.

When an enzyme tries to add a methyl group to silence decitabine, the drug traps it in place, preventing methylation. This triggers another group of enzymes to transform a methylated cytosine on the parent DNA strand into 5hmC, a molecule whose biological function is not yet known.

The investigators confirmed the increase in 5hmC levels in decitabine-treated leukemia cells.

To better explain the team’s findings, Basudev Chowdhury, PhD, also of Purdue University, likened decitabine to a text editor that restores meaning to a garbled sentence and compared conventional chemotherapy to a delete button.

“Think of nucleotides as the alphabet with which our cells compose messages,” he said. “Epigenetics helps translate those messages into actions such as the production of proteins. But cancer can jumble the messages, making them nonsensical. Decitabine helps revise the messages so they can be understood.”

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

Patient receives chemotherapy

Photo by Rhoda Baer

Survivors of Hodgkin lymphoma (HL) have an increased risk of developing cardiovascular diseases throughout their lives, according to a study published in JAMA Internal Medicine.

Previous research suggested that HL treatment is associated with an increased risk of cardiovascular diseases.

However, those studies did not determine how long the increased risk persists or pinpoint the risk factors for various cardiovascular diseases.

So Flora E. van Leeuwen, PhD, of the Netherlands Cancer Institute in Amsterdam, and her colleagues decided to investigate.

The team examined the risk for cardiovascular disease in HL survivors up to 40 years after they received treatment and compared that with the risk for cardiovascular disease in the general population. The researchers also studied treatment-related risk factors.

The study included 2524 Dutch patients who were diagnosed with HL when they were younger than 51 years of age. The patients’ median age was 27.3 years.

The patients were treated from 1965 through 1995 and had survived for at least 5 years after diagnosis. In all, 2052 patients (81.3%) had received mediastinal radiotherapy, and 773 (30.6%) had received chemotherapy containing an anthracycline.

At a median of 20.3 years of follow-up, there were 1713 cardiovascular events in 797 patients (31.6%), and 410 of those patients (51.4%) had experienced 2 events or more.

The most frequently occurring cardiovascular disease was coronary heart disease (CHD), with 401 patients developing it as their first event. This was followed by valvular heart disease (VHD, 374 events) and heart failure (HF, 140 events).

HL survivors had a 3.2-fold increased risk of developing CHD and a 6.8-fold increased risk of developing HF compared to the general population.

HL survivors who had been treated before age 25 had a 4.6-fold to 7.5-fold increased risk of CHD and a 10.9-fold to 40.5-fold increased risk of HF, depending on the age they ultimately attained.

HL survivors treated at 35 to 50 years of age had a 2.0-fold to 2.3-fold increased risk of CHD and a 3.1-fold to 5.2-fold increased risk of HF, depending on their attained age.

The risks of CHD and HF remained significantly increased beyond 35 years after HL treatment. The standardized incidence ratios were 3.9 and 5.8, respectively.

The median times between HL treatment and first cardiovascular disease events were 18 years for CHD, 24 years for VHD, and 19 years for HF.

The cumulative risk of any type of cardiovascular disease was 50% at 40 years after HL diagnosis. For patients who were treated for HL before they were 25, the cumulative risk of developing a cardiovascular disease at 60 years of age or older was 20% for CHD, 31% for VHD, and 11% for HF.

The study also suggested that mediastinal radiotherapy increased the risk of CHD, VHD, and HF. But anthracycline-containing chemotherapy only increased the risk of VHD and HF.

Dr van Leeuwen and her colleagues concluded that both physicians and patients should be aware that HL survivors have a persistently increased risk of developing cardiovascular diseases throughout their lives. The team also believes the results of their study may direct guidelines for follow-up in HL survivors.

A commentary related to this research is available in JAMA Internal Medicine as well.

Prescription medications

Photo courtesy of the CDC

Celgene Corporation has fulfilled the requirements for accelerated approval of pomalidomide (Pomalyst) in the US, based on results from the phase 3 MM-003 trial.

The trial showed that pomalidomide in combination with dexamethasone can improve survival in patients with relapsed or refractory multiple

myeloma (MM).

A drug can be granted accelerated approval in the US based on a surrogate endpoint thought to predict clinical benefit.

To retain approval from the US Food and Drug Administration (FDA), the drug must demonstrate an actual clinical benefit.

In 2013, the FDA granted pomalidomide accelerated approval for use in combination with dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or within 60 days of completing their last therapy.

The FDA’s approval was based on results from a phase 2 trial known as MM-002. The trial showed that pomalidomide plus dexamethasone can improve the overall response rate in relapsed/refractory MM patients when compared to pomalidomide alone.

About 29% of patients in the pomalidomide-dexamethasone arm achieved a partial response or better, compared to about 7% of patients in the pomalidomide-alone arm.

Now, results of the MM-003 trial have shown that pomalidomide plus low-dose dexamethasone can improve progression-free survival and overall survival in relapsed/refractory MM patients, when compared to high-dose dexamethasone alone.

The median progression-free survival was 3.6 months in the pomalidomide-dexamethasone arm and 1.8 months in the dexamethasone arm (P<0.001). And the median overall survival was 12.4 months and 8 months, respectively (P=0.009).

These outcomes suggest pomalidomide, in combination with dexamethasone, provides a clinical benefit for previously treated MM patients, which fulfills the requirements for accelerated approval. So the drug’s label has been updated to reflect his change.

For more details on pomalidomide, see the full prescribing information.

Prescription medications

Photo courtesy of the CDC

Celgene Corporation has fulfilled the requirements for accelerated approval of pomalidomide (Pomalyst) in the US, based on results from the phase 3 MM-003 trial.

The trial showed that pomalidomide in combination with dexamethasone can improve survival in patients with relapsed or refractory multiple

myeloma (MM).

A drug can be granted accelerated approval in the US based on a surrogate endpoint thought to predict clinical benefit.

To retain approval from the US Food and Drug Administration (FDA), the drug must demonstrate an actual clinical benefit.

In 2013, the FDA granted pomalidomide accelerated approval for use in combination with dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or within 60 days of completing their last therapy.

The FDA’s approval was based on results from a phase 2 trial known as MM-002. The trial showed that pomalidomide plus dexamethasone can improve the overall response rate in relapsed/refractory MM patients when compared to pomalidomide alone.

About 29% of patients in the pomalidomide-dexamethasone arm achieved a partial response or better, compared to about 7% of patients in the pomalidomide-alone arm.

Now, results of the MM-003 trial have shown that pomalidomide plus low-dose dexamethasone can improve progression-free survival and overall survival in relapsed/refractory MM patients, when compared to high-dose dexamethasone alone.

The median progression-free survival was 3.6 months in the pomalidomide-dexamethasone arm and 1.8 months in the dexamethasone arm (P<0.001). And the median overall survival was 12.4 months and 8 months, respectively (P=0.009).

These outcomes suggest pomalidomide, in combination with dexamethasone, provides a clinical benefit for previously treated MM patients, which fulfills the requirements for accelerated approval. So the drug’s label has been updated to reflect his change.

For more details on pomalidomide, see the full prescribing information.

Prescription medications

Photo courtesy of the CDC

Celgene Corporation has fulfilled the requirements for accelerated approval of pomalidomide (Pomalyst) in the US, based on results from the phase 3 MM-003 trial.

The trial showed that pomalidomide in combination with dexamethasone can improve survival in patients with relapsed or refractory multiple

myeloma (MM).

A drug can be granted accelerated approval in the US based on a surrogate endpoint thought to predict clinical benefit.

To retain approval from the US Food and Drug Administration (FDA), the drug must demonstrate an actual clinical benefit.

In 2013, the FDA granted pomalidomide accelerated approval for use in combination with dexamethasone to treat MM patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or within 60 days of completing their last therapy.

The FDA’s approval was based on results from a phase 2 trial known as MM-002. The trial showed that pomalidomide plus dexamethasone can improve the overall response rate in relapsed/refractory MM patients when compared to pomalidomide alone.

About 29% of patients in the pomalidomide-dexamethasone arm achieved a partial response or better, compared to about 7% of patients in the pomalidomide-alone arm.

Now, results of the MM-003 trial have shown that pomalidomide plus low-dose dexamethasone can improve progression-free survival and overall survival in relapsed/refractory MM patients, when compared to high-dose dexamethasone alone.

The median progression-free survival was 3.6 months in the pomalidomide-dexamethasone arm and 1.8 months in the dexamethasone arm (P<0.001). And the median overall survival was 12.4 months and 8 months, respectively (P=0.009).

These outcomes suggest pomalidomide, in combination with dexamethasone, provides a clinical benefit for previously treated MM patients, which fulfills the requirements for accelerated approval. So the drug’s label has been updated to reflect his change.

For more details on pomalidomide, see the full prescribing information.

A recombinant factor VIII Fc fusion protein (rFVIIIFc/efmoroctocog alfa, Eloctate/Elocta) can prevent and control bleeding in previously treated children with severe hemophilia A, results of the phase 3 KIDS A-LONG study suggest.

Children who were previously receiving factor VIII prophylaxis saw their median annualized bleeding rate (ABR) decrease with rFVIIIFc, and close to half of the children on this study did not have any bleeding episodes while they were receiving rFVIIIFc.

None of the patients developed inhibitors to rFVIIIFc. And researchers said adverse events on this trial were typical of a pediatric hemophilia population.

The team reported these results in the Journal of Thrombosis and Haemostasis. The trial was sponsored by Biogen Idec and Sobi, the companies developing rFVIIIFc.

The study included 71 boys younger than 12 years of age who had severe hemophilia A. The patients had at least 50 prior exposure days to factor VIII and no history of factor VIII inhibitors.

The children were set to receive twice-weekly prophylactic infusions of rFVIIIFc, 25 IU/kg on day 1 and 50 IU/kg on day 4, but the researchers made adjustments to dosing as needed.

The median average weekly rFVIIIFc prophylactic dose was 88.11 IU kg. About 90% of the patients were on twice-weekly dosing at the end of the study. Seventy-four percent of patients were able to reduce their dosing frequency with rFVIIIFc compared to factor VIII prophylaxis.

About 46% of patients did not have any bleeding events on study. The median ABR was 1.96 overall and 0 for spontaneous and traumatic bleeding episodes, as well as for spontaneous joint bleeding episodes.

Among patients who were previously receiving factor VIII prophylaxis, their median ABR decreased with rFVIIIFc. For children younger than 6 years of age, the median ABR fell from 1.50 to 0. For children ages 6 through 11, the median ABR fell from 2.50 to 2.01.

About 86% of patients had at least one adverse event while on rFVIIIFc, but none of them discontinued treatment as a result.

Two non-serious events (myalgia and erythematous rash) were considered related to rFVIIIFc. And 5 patients experienced 7 serious adverse events that were not related to treatment.

A recombinant factor VIII Fc fusion protein (rFVIIIFc/efmoroctocog alfa, Eloctate/Elocta) can prevent and control bleeding in previously treated children with severe hemophilia A, results of the phase 3 KIDS A-LONG study suggest.

Children who were previously receiving factor VIII prophylaxis saw their median annualized bleeding rate (ABR) decrease with rFVIIIFc, and close to half of the children on this study did not have any bleeding episodes while they were receiving rFVIIIFc.

None of the patients developed inhibitors to rFVIIIFc. And researchers said adverse events on this trial were typical of a pediatric hemophilia population.

The team reported these results in the Journal of Thrombosis and Haemostasis. The trial was sponsored by Biogen Idec and Sobi, the companies developing rFVIIIFc.

The study included 71 boys younger than 12 years of age who had severe hemophilia A. The patients had at least 50 prior exposure days to factor VIII and no history of factor VIII inhibitors.

The children were set to receive twice-weekly prophylactic infusions of rFVIIIFc, 25 IU/kg on day 1 and 50 IU/kg on day 4, but the researchers made adjustments to dosing as needed.

The median average weekly rFVIIIFc prophylactic dose was 88.11 IU kg. About 90% of the patients were on twice-weekly dosing at the end of the study. Seventy-four percent of patients were able to reduce their dosing frequency with rFVIIIFc compared to factor VIII prophylaxis.

About 46% of patients did not have any bleeding events on study. The median ABR was 1.96 overall and 0 for spontaneous and traumatic bleeding episodes, as well as for spontaneous joint bleeding episodes.

Among patients who were previously receiving factor VIII prophylaxis, their median ABR decreased with rFVIIIFc. For children younger than 6 years of age, the median ABR fell from 1.50 to 0. For children ages 6 through 11, the median ABR fell from 2.50 to 2.01.

About 86% of patients had at least one adverse event while on rFVIIIFc, but none of them discontinued treatment as a result.

Two non-serious events (myalgia and erythematous rash) were considered related to rFVIIIFc. And 5 patients experienced 7 serious adverse events that were not related to treatment.

A recombinant factor VIII Fc fusion protein (rFVIIIFc/efmoroctocog alfa, Eloctate/Elocta) can prevent and control bleeding in previously treated children with severe hemophilia A, results of the phase 3 KIDS A-LONG study suggest.

Children who were previously receiving factor VIII prophylaxis saw their median annualized bleeding rate (ABR) decrease with rFVIIIFc, and close to half of the children on this study did not have any bleeding episodes while they were receiving rFVIIIFc.

None of the patients developed inhibitors to rFVIIIFc. And researchers said adverse events on this trial were typical of a pediatric hemophilia population.

The team reported these results in the Journal of Thrombosis and Haemostasis. The trial was sponsored by Biogen Idec and Sobi, the companies developing rFVIIIFc.

The study included 71 boys younger than 12 years of age who had severe hemophilia A. The patients had at least 50 prior exposure days to factor VIII and no history of factor VIII inhibitors.

The children were set to receive twice-weekly prophylactic infusions of rFVIIIFc, 25 IU/kg on day 1 and 50 IU/kg on day 4, but the researchers made adjustments to dosing as needed.

The median average weekly rFVIIIFc prophylactic dose was 88.11 IU kg. About 90% of the patients were on twice-weekly dosing at the end of the study. Seventy-four percent of patients were able to reduce their dosing frequency with rFVIIIFc compared to factor VIII prophylaxis.

About 46% of patients did not have any bleeding events on study. The median ABR was 1.96 overall and 0 for spontaneous and traumatic bleeding episodes, as well as for spontaneous joint bleeding episodes.

Among patients who were previously receiving factor VIII prophylaxis, their median ABR decreased with rFVIIIFc. For children younger than 6 years of age, the median ABR fell from 1.50 to 0. For children ages 6 through 11, the median ABR fell from 2.50 to 2.01.

About 86% of patients had at least one adverse event while on rFVIIIFc, but none of them discontinued treatment as a result.

Two non-serious events (myalgia and erythematous rash) were considered related to rFVIIIFc. And 5 patients experienced 7 serious adverse events that were not related to treatment.

Vials of chemotherapy drugs

Photo by Bill Branson

The pharmaceutical company Mylan is conducting a US-wide recall of several injectable chemotherapy drugs.

Testing of retention samples revealed foreign particulate matter in lots of gemcitabine, carboplatin, methotrexate, and cytarabine. So Mylan issued a

recall of these lots to the hospital/user level.

To date, Mylan has not received any reports of adverse events related to this recall. However, administering injectables that contain foreign particulates can have severe consequences.

Intrathecal administration could result in a life-threatening adverse event or permanent impairment of a body function. Intravenous administration has the potential to damage and/or obstruct blood vessels, which could induce emboli, particularly in the lungs. Intravenous injection can also result in local inflammation, phlebitis, allergic response, and/or embolization in the body and infection.

Intra-arterial administration could result in damage to blood vessels in the distal extremities or organs. And intramuscular administration could result in foreign-body inflammatory response, with local pain, swelling, and possible long-term granuloma formation.

Recall details

The following drugs are included in this recall:

• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801396; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801401; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 0069-3857-10; Lot number: 7801089; Expiration date: 07/2015
• Gemcitabine for Injection, USP 2 g; 100 mL; NDC number: 67457-463-02; Lot number: 7801222; Expiration date: 03/2016
• Gemcitabine for Injection, USP 1 g; 50 mL; NDC number: 67457-462-01; Lot number: 7801273;        Expiration date: 05/2016
• Carboplatin Injection 10 mg/mL; 100 mL; NDC number: 67457-493-46; Lot number: 7801312; Expiration date: 06/2015
• Methotrexate Injection, USP 25 mg/mL; 2 mL (5 x 2 mL); NDC number: 0069-0146-02; Lot number: 7801082; Expiration date: 07/2015
• Cytarabine Injection 20 mg/mL; 5 mL (10 x 5mL); NDC number: 0069-0152-02; Lot number: 7801050; Expiration date: 05/2015.

Gemcitabine for Injection, USP 200 mg is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between February 18, 2014, and December 19, 2014, and were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801089 is packaged with a Pfizer Injectable label.

Carboplatin Injection 10 mg/mL is an intravenously administered product indicated for the treatment of advanced ovarian carcinoma. The lot was distributed in the US between August 11, 2014, and October 7, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Mylan Institutional label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between January 16, 2014, and March 25, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Pfizer Injectables label.

Cytarabine Injection can be administered intravenously or intrathecally and in combination with other approved anticancer drugs. Cytarabine is indicated for remission induction in acute non-lymphocytic leukemia in adults and pediatric patients. The lot was distributed in the US between May 02, 2014, and July 24, 2014, and was manufactured and packaged by Agila Onco Therapies Limited, a Mylan company located in Bangalore, India, and is packaged with a Pfizer Injectables label.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with the recalled products should stop using them and return them to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 1-800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST.

Consumers should contact their physicians or healthcare providers if they have experienced any problems that may be related to using these drugs.

Adverse reactions or quality problems related to the use of these product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Vials of chemotherapy drugs

Photo by Bill Branson

The pharmaceutical company Mylan is conducting a US-wide recall of several injectable chemotherapy drugs.

Testing of retention samples revealed foreign particulate matter in lots of gemcitabine, carboplatin, methotrexate, and cytarabine. So Mylan issued a

recall of these lots to the hospital/user level.

To date, Mylan has not received any reports of adverse events related to this recall. However, administering injectables that contain foreign particulates can have severe consequences.

Intrathecal administration could result in a life-threatening adverse event or permanent impairment of a body function. Intravenous administration has the potential to damage and/or obstruct blood vessels, which could induce emboli, particularly in the lungs. Intravenous injection can also result in local inflammation, phlebitis, allergic response, and/or embolization in the body and infection.

Intra-arterial administration could result in damage to blood vessels in the distal extremities or organs. And intramuscular administration could result in foreign-body inflammatory response, with local pain, swelling, and possible long-term granuloma formation.

Recall details

The following drugs are included in this recall:

• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801396; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801401; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 0069-3857-10; Lot number: 7801089; Expiration date: 07/2015
• Gemcitabine for Injection, USP 2 g; 100 mL; NDC number: 67457-463-02; Lot number: 7801222; Expiration date: 03/2016
• Gemcitabine for Injection, USP 1 g; 50 mL; NDC number: 67457-462-01; Lot number: 7801273;        Expiration date: 05/2016
• Carboplatin Injection 10 mg/mL; 100 mL; NDC number: 67457-493-46; Lot number: 7801312; Expiration date: 06/2015
• Methotrexate Injection, USP 25 mg/mL; 2 mL (5 x 2 mL); NDC number: 0069-0146-02; Lot number: 7801082; Expiration date: 07/2015
• Cytarabine Injection 20 mg/mL; 5 mL (10 x 5mL); NDC number: 0069-0152-02; Lot number: 7801050; Expiration date: 05/2015.

Gemcitabine for Injection, USP 200 mg is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between February 18, 2014, and December 19, 2014, and were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801089 is packaged with a Pfizer Injectable label.

Carboplatin Injection 10 mg/mL is an intravenously administered product indicated for the treatment of advanced ovarian carcinoma. The lot was distributed in the US between August 11, 2014, and October 7, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Mylan Institutional label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between January 16, 2014, and March 25, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Pfizer Injectables label.

Cytarabine Injection can be administered intravenously or intrathecally and in combination with other approved anticancer drugs. Cytarabine is indicated for remission induction in acute non-lymphocytic leukemia in adults and pediatric patients. The lot was distributed in the US between May 02, 2014, and July 24, 2014, and was manufactured and packaged by Agila Onco Therapies Limited, a Mylan company located in Bangalore, India, and is packaged with a Pfizer Injectables label.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with the recalled products should stop using them and return them to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 1-800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST.

Consumers should contact their physicians or healthcare providers if they have experienced any problems that may be related to using these drugs.

Adverse reactions or quality problems related to the use of these product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Vials of chemotherapy drugs

Photo by Bill Branson

The pharmaceutical company Mylan is conducting a US-wide recall of several injectable chemotherapy drugs.

Testing of retention samples revealed foreign particulate matter in lots of gemcitabine, carboplatin, methotrexate, and cytarabine. So Mylan issued a

recall of these lots to the hospital/user level.

To date, Mylan has not received any reports of adverse events related to this recall. However, administering injectables that contain foreign particulates can have severe consequences.

Intrathecal administration could result in a life-threatening adverse event or permanent impairment of a body function. Intravenous administration has the potential to damage and/or obstruct blood vessels, which could induce emboli, particularly in the lungs. Intravenous injection can also result in local inflammation, phlebitis, allergic response, and/or embolization in the body and infection.

Intra-arterial administration could result in damage to blood vessels in the distal extremities or organs. And intramuscular administration could result in foreign-body inflammatory response, with local pain, swelling, and possible long-term granuloma formation.

Recall details

The following drugs are included in this recall:

• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801396; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 67457-464-20; Lot number: 7801401; Expiration date: 08/2016
• Gemcitabine for Injection, USP 200 mg; 10 mL; NDC number: 0069-3857-10; Lot number: 7801089; Expiration date: 07/2015
• Gemcitabine for Injection, USP 2 g; 100 mL; NDC number: 67457-463-02; Lot number: 7801222; Expiration date: 03/2016
• Gemcitabine for Injection, USP 1 g; 50 mL; NDC number: 67457-462-01; Lot number: 7801273;        Expiration date: 05/2016
• Carboplatin Injection 10 mg/mL; 100 mL; NDC number: 67457-493-46; Lot number: 7801312; Expiration date: 06/2015
• Methotrexate Injection, USP 25 mg/mL; 2 mL (5 x 2 mL); NDC number: 0069-0146-02; Lot number: 7801082; Expiration date: 07/2015
• Cytarabine Injection 20 mg/mL; 5 mL (10 x 5mL); NDC number: 0069-0152-02; Lot number: 7801050; Expiration date: 05/2015.

Gemcitabine for Injection, USP 200 mg is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer, and pancreatic cancer. These lots were distributed in the US between February 18, 2014, and December 19, 2014, and were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801089 is packaged with a Pfizer Injectable label.

Carboplatin Injection 10 mg/mL is an intravenously administered product indicated for the treatment of advanced ovarian carcinoma. The lot was distributed in the US between August 11, 2014, and October 7, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Mylan Institutional label.

Methotrexate Injection, USP 25 mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. The lot was distributed in the US between January 16, 2014, and March 25, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Pfizer Injectables label.

Cytarabine Injection can be administered intravenously or intrathecally and in combination with other approved anticancer drugs. Cytarabine is indicated for remission induction in acute non-lymphocytic leukemia in adults and pediatric patients. The lot was distributed in the US between May 02, 2014, and July 24, 2014, and was manufactured and packaged by Agila Onco Therapies Limited, a Mylan company located in Bangalore, India, and is packaged with a Pfizer Injectables label.

Mylan is notifying its distributors and customers by letter and is arranging for the return of all recalled products. Distributors, retailers, hospitals, clinics, and physicians with the recalled products should stop using them and return them to the place of purchase.

Consumers with questions regarding this recall can contact Mylan Customer Relations at 1-800-796-9526 or [email protected], Monday through Friday from 8 am to 5 pm EST.

Consumers should contact their physicians or healthcare providers if they have experienced any problems that may be related to using these drugs.

Adverse reactions or quality problems related to the use of these product may be reported to the US Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

KISSIMMEE, FLA. – Fractional carbon dioxide laser resurfacing followed by 30 minutes of aminolevulinic acid plus blue light photodynamic therapy cleared 94% of actinic keratoses, significantly more than ALA-PDT alone, according to the findings of a randomized, single-blinded, split-face study of 20 patients.

Laser resurfacing was associated with worse short-term erythema, but erythema resolved in about 7 days and was not associated with other adverse events, Dr. Macrene Alexiades-Armenakas said at the annual meeting of the American Society for Laser Medicine and Surgery.

Historically, two sessions of 20% topical ALA and blue light PDT have yielded actinic keratosis cure rates of 78% to 89%, but only with ALA incubation times of 14-18 hours, said Dr. Alexiades-Armenakas, associate clinical professor at Yale University, New Haven, Conn.

©Dr-Strangelove/ThinkStockPhotos.com

“Increasing drug penetration may serve to enhance PDT efficacy and shorten incubation time,” she said.

To test that hypothesis, she compared the safety and efficacy of 15- and 30-minute incubations of ALA and blue light PDT, with or without CO₂ laser resurfacing. After cleaning patients’ faces with acetone wipes and applying a topical anesthetic for 1 hour, she randomly selected one half of each patient’s face for pretreatment with fractional CO₂ laser, using settings of 15-28 W, 500 mcm dot spacing, and 600-800 microsecond dwell time.

Next, she applied 5-ALA to the entire face, then performed blue light illumination for 1,000 seconds. Half of the 20 patients were randomly assigned ALA incubation times of 15 minutes, while the other half underwent 30-minute incubations. She rechecked patients at 1 week, 4 weeks, and 8 weeks, and took digital photographs at baseline and at each recheck using identical lighting conditions. A blinded evaluator scored each side of each face, defining clearance as complete regression of actinic keratosis.

At 8 weeks, the rate of complete clearance for the 10 patients who underwent 15-minute ALA incubations was 88% for laser resurfacing followed by ALA-PDT, compared with 74% for ALA-PDT alone (P < .05), Dr. Alexiades-Armenakas reported. Clearance rates for the 30-minute incubation group were 94% for laser followed by ALA-PDT and 82% for ALA-PDT alone (P < .05).

Skin treated only with ALA-PDT developed minimal to moderate erythema that resolved within 5-7 days for all patients, but the laser-resurfaced skin developed “moderate to significant” erythema that resolved within 5-7 days with home care, she said.

Taken together, the results indicate that fractional CO₂ laser treatment yields safe and effective clearance of actinic keratoses with “ultra-short” incubation times, Dr. Alexiades-Armenakas said.

Deka manufactures the fractional CO₂ laser tested in the study, and DUSA Pharmaceuticals manufactures the blue light PDT device and the ALA product. Dr. Alexiades-Armenakas reported receiving clinical research grants from Deka, DUSA Pharmaceuticals, Alma, and Syneron.

KISSIMMEE, FLA. – Fractional carbon dioxide laser resurfacing followed by 30 minutes of aminolevulinic acid plus blue light photodynamic therapy cleared 94% of actinic keratoses, significantly more than ALA-PDT alone, according to the findings of a randomized, single-blinded, split-face study of 20 patients.

Laser resurfacing was associated with worse short-term erythema, but erythema resolved in about 7 days and was not associated with other adverse events, Dr. Macrene Alexiades-Armenakas said at the annual meeting of the American Society for Laser Medicine and Surgery.

Historically, two sessions of 20% topical ALA and blue light PDT have yielded actinic keratosis cure rates of 78% to 89%, but only with ALA incubation times of 14-18 hours, said Dr. Alexiades-Armenakas, associate clinical professor at Yale University, New Haven, Conn.

©Dr-Strangelove/ThinkStockPhotos.com

“Increasing drug penetration may serve to enhance PDT efficacy and shorten incubation time,” she said.

To test that hypothesis, she compared the safety and efficacy of 15- and 30-minute incubations of ALA and blue light PDT, with or without CO₂ laser resurfacing. After cleaning patients’ faces with acetone wipes and applying a topical anesthetic for 1 hour, she randomly selected one half of each patient’s face for pretreatment with fractional CO₂ laser, using settings of 15-28 W, 500 mcm dot spacing, and 600-800 microsecond dwell time.

Next, she applied 5-ALA to the entire face, then performed blue light illumination for 1,000 seconds. Half of the 20 patients were randomly assigned ALA incubation times of 15 minutes, while the other half underwent 30-minute incubations. She rechecked patients at 1 week, 4 weeks, and 8 weeks, and took digital photographs at baseline and at each recheck using identical lighting conditions. A blinded evaluator scored each side of each face, defining clearance as complete regression of actinic keratosis.

At 8 weeks, the rate of complete clearance for the 10 patients who underwent 15-minute ALA incubations was 88% for laser resurfacing followed by ALA-PDT, compared with 74% for ALA-PDT alone (P < .05), Dr. Alexiades-Armenakas reported. Clearance rates for the 30-minute incubation group were 94% for laser followed by ALA-PDT and 82% for ALA-PDT alone (P < .05).

Skin treated only with ALA-PDT developed minimal to moderate erythema that resolved within 5-7 days for all patients, but the laser-resurfaced skin developed “moderate to significant” erythema that resolved within 5-7 days with home care, she said.

Taken together, the results indicate that fractional CO₂ laser treatment yields safe and effective clearance of actinic keratoses with “ultra-short” incubation times, Dr. Alexiades-Armenakas said.

Deka manufactures the fractional CO₂ laser tested in the study, and DUSA Pharmaceuticals manufactures the blue light PDT device and the ALA product. Dr. Alexiades-Armenakas reported receiving clinical research grants from Deka, DUSA Pharmaceuticals, Alma, and Syneron.

KISSIMMEE, FLA. – Fractional carbon dioxide laser resurfacing followed by 30 minutes of aminolevulinic acid plus blue light photodynamic therapy cleared 94% of actinic keratoses, significantly more than ALA-PDT alone, according to the findings of a randomized, single-blinded, split-face study of 20 patients.

Laser resurfacing was associated with worse short-term erythema, but erythema resolved in about 7 days and was not associated with other adverse events, Dr. Macrene Alexiades-Armenakas said at the annual meeting of the American Society for Laser Medicine and Surgery.

Historically, two sessions of 20% topical ALA and blue light PDT have yielded actinic keratosis cure rates of 78% to 89%, but only with ALA incubation times of 14-18 hours, said Dr. Alexiades-Armenakas, associate clinical professor at Yale University, New Haven, Conn.

©Dr-Strangelove/ThinkStockPhotos.com

“Increasing drug penetration may serve to enhance PDT efficacy and shorten incubation time,” she said.

To test that hypothesis, she compared the safety and efficacy of 15- and 30-minute incubations of ALA and blue light PDT, with or without CO₂ laser resurfacing. After cleaning patients’ faces with acetone wipes and applying a topical anesthetic for 1 hour, she randomly selected one half of each patient’s face for pretreatment with fractional CO₂ laser, using settings of 15-28 W, 500 mcm dot spacing, and 600-800 microsecond dwell time.

Next, she applied 5-ALA to the entire face, then performed blue light illumination for 1,000 seconds. Half of the 20 patients were randomly assigned ALA incubation times of 15 minutes, while the other half underwent 30-minute incubations. She rechecked patients at 1 week, 4 weeks, and 8 weeks, and took digital photographs at baseline and at each recheck using identical lighting conditions. A blinded evaluator scored each side of each face, defining clearance as complete regression of actinic keratosis.

At 8 weeks, the rate of complete clearance for the 10 patients who underwent 15-minute ALA incubations was 88% for laser resurfacing followed by ALA-PDT, compared with 74% for ALA-PDT alone (P < .05), Dr. Alexiades-Armenakas reported. Clearance rates for the 30-minute incubation group were 94% for laser followed by ALA-PDT and 82% for ALA-PDT alone (P < .05).

Skin treated only with ALA-PDT developed minimal to moderate erythema that resolved within 5-7 days for all patients, but the laser-resurfaced skin developed “moderate to significant” erythema that resolved within 5-7 days with home care, she said.

Taken together, the results indicate that fractional CO₂ laser treatment yields safe and effective clearance of actinic keratoses with “ultra-short” incubation times, Dr. Alexiades-Armenakas said.

Deka manufactures the fractional CO₂ laser tested in the study, and DUSA Pharmaceuticals manufactures the blue light PDT device and the ALA product. Dr. Alexiades-Armenakas reported receiving clinical research grants from Deka, DUSA Pharmaceuticals, Alma, and Syneron.