FDA Panel Approves Imatinib for Pediatric ALL....

The US Food and Drug Administration (FDA) today approved imatinib (Gleevec, Novartis) for the treatment of newly diagnosed pediatric acute lymphoblastic leukemia (ALL) that is Philadelphia chromosome (Ph) positive.
"We are pleased that the number of cancer medications for children is on the rise," said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products at the FDA Center for Drug Evaluation and Research, in a press statement.
In 2011, imatinib was approved to treat children newly diagnosed with Ph-positive chronic myeloid leukemia (CML).
However, ALL is the most common type of pediatric cancer, affecting approximately 2900 children annually, according to the FDA.
The safety and effectiveness of imatinib for pediatric patients with Ph-positive ALL were established in a clinical trial that enrolled children (1 year and older) and young adults with very-high-risk ALL (>45% chance of experiencing complications from their disease within 5 years of treatment).
The 92 patients with Ph-positive ALL enrolled in the trial were divided into 5 treatment groups, with each successive group receiving imatinib plus chemotherapy for a longer period.
Fifty of the Ph-positive ALL patients received imatinib for the longest period, and 70% of these patients did not experience relapse or death within 4 years. In addition, patient deaths decreased with the increasing duration of imatinib treatment in combination with chemotherapy, according to the FDA.
The most common adverse effects observed in children with Ph-positive ALL treated with imatinib plus chemotherapy were decreased neutrophil levels, decreased blood platelets levels, liver toxicity, and infection.
Imatinib is a tyrosine kinase inhibitor that blocks cancer-promoting proteins, and should be used in combination with chemotherapy to treat pediatric Ph-positive ALL.

Imatinib has been a practice-changing drug in this setting, according to the Children's Oncology Group, which conducted the pivotal clinical trial.
According to the group's Web site, the preferred treatment for Ph-positive ALL before imatinib was stem cell transplantation followed by 3 to 6 months of chemotherapy. However, cure rates were less than 50% with this approach. Imatinib in combination with chemotherapy has doubled cure rates, and stem cell transplantation is no longer automatically considered to be the best way to treat children with Ph-positive ALL.
Imatinib was granted accelerated approval in 2001 by the FDA to treat patients with blast-crisis, accelerated-phase, or chronic-phase Ph-positive CML who have failed interferon-alpha therapy. The drug was also approved in 2012 for the treatment of adults whose Kit (CD117)-positive gastrointestinal stromal tumors (GIST) had been surgically removed.

FDA Panel Calls for Greater Restriction on Hydrocodone....

Drugs containing hydrocodone combined with other analgesics may soon be subject to more stringent prescribing requirements if the US Food and Drug Administration (FDA) accepts the recommendation of its expert panel to reschedule the widely used drug.
The FDA's Drug Safety and Risk Management Advisory Committee voted 19 to 10 in favor of reclassifying hydrocodone-containing compounds from Schedule III drugs under the Controlled Substances Act to Schedule II.
For 2 days, the panel heard impassioned testimony for and against reclassification, with those in favor emphasizing hydrocodone's potential for addiction and abuse, and those against warning that millions of legitimate pain patients would suffer if its availability becomes more limited.
The vote sends a strong message to physicians and the public about the abuse potential of hydrocodone combination products, many of the panel felt. Several mentioned the fact that death rates from hydrocodone combination drug overdoses have tripled during the last 2 decades
"Clearly, the data show the magnitude of the epidemic of misuse, abuse, and diversion of prescription narcotics," said Elaine Morrato, DrPH, from the University of Colorado School of Public Health, in Aurora, in explaining her yes vote.
"For me, the most persuasive argument was that rescheduling is a signal to the public as well as to the medical profession about the abuse potential, and it rights a misperception that hydrocodone combination products are safer options than class IIs when it comes to long-term risk of abuse," Dr. Morrato said.
She added that she was hopeful that "appropriate remedies" would be put in place should the rescheduling be implemented, "so that those who are disadvantaged, such as those who are in rural settings or who may have access problems, aren't disproportionately affected by the change."
Curbing Early Abuse
William Cooper, MD, MPH, professor of pediatrics and preventive medicine at Vanderbilt University School of Medicine, Nashville, Tennessee, also voted yes for similar reasons.
"I too considered the potential impact on patients and providers, and that is an important issue for us to consider as we move forward," Dr. Cooper said. "But there is clear and compelling evidence that there is severe dependence on these medications among those who abuse them."
He added that, as a pediatrician, "I would urge us from the public health perspective to be mindful that much of our data suggest abuse can begin in adolescents and young adults, and we need to think carefully about prevention measures in this age group and do what we can to prevent this scourge."
Melinda Moore, a physician assistant from Webster, Texas, was against rescheduling because she feared that the burden to patients, especially in rural areas, would be greatly increased.
"The inability to call in prescriptions for the hydrocodone combination was one of my major problems with rescheduling. I felt there were poor data to support the change," she said.
Moore stressed the importance of monitoring drug use and that such monitoring programs should be across state lines and widely used. She also suggested that steps such as electronic prescribing should be in all states for all schedules, including 2 through 5.
Hobson's Choice
Another strong opponent to rescheduling was John Mendelson, MD, from St. Luke's Hospital, San Francisco, California.

"This is a Hobson's choice. There is no good single choice within this vote, which is unfortunate. I believe that the net result will be increased prescribing of other C2 drugs which may have greater abuse liability and actually fuel, rather than reduce, an epidemic in progress," Dr. Mendelson said. "Illicit opiate use will increase with dire consequences."
A final complication that is likely from this vote is that some people will be abruptly withdrawn, he predicted.
"We have already heard from dramatic testimony today exactly how dangerous abrupt opiate withdrawal is with later recrudescence to opiate abuse. At least 2 of the deaths that we heard about today were directly related to those issues."
Center for Drug Evaluation and Research Meeting of the Drug Safety and Risk Management Advisory Committee, Silver Spring, Maryland, January 24-25, 2013.