Child Cancer Survival Imperiled by Lack of New Drugs

Improving childhood cancer survival rates is being stymied by regulatory burdens and stagnant research approaches, U.S. and European doctors said.

While five-year survival rates climbed to 80 percent in the 2000s, from 30 percent in the 1960s, the needle is no longer making leaps, the doctors wrote in the journal Lancet Oncology. Patients also face severe and lasting side effects that have yet to be fully addressed, according to the article series called “Improving Cancer Care for Children and Young People.”

Cancer is the most common cause of death from disease in children beyond infancy who live in high-income countries, second only to accidents, according to the articles. In developing countries the situation is more dire, with four-fifths of pediatric cancer patients in Africa dying.

“There needs to be a recognition that childhood cancer is a global problem,” Gregory Reaman, an associate director at the U.S. Food and Drug Administration’s Office of Hematology and Oncology Products, said in a telephone interview. “There needs to be more international collaboration in clinical research.”

Headway is dependent on modernizing regulations and drug research in richer countries, and increasing access to treatment in developing countries, the oncologists wrote. Drugmakers now typically gain clearance for cancer medicines in adults first and then take the time to learn more about the drugs’ potential in younger patients, a smaller and less profitable market.

That approach had led to only 15 such medicines being allowed for use in children since 1998, according to data used at a December meeting that the FDA held on four experimental treatments that may one day help pediatric patients.

Novartis’s Gleevec

The medicines that were the topic of discussion that day came from GlaxoSmithKline Plc, Amgen Inc., Threshold Pharmaceuticals Inc. and Boehringer Ingelheim GmbH.

Researchers have had trouble in the past translating advances in adult research into pediatric oncology, according to the articles.

Novartis AG’s Gleevec, first approved in 2001, was granted U.S. approval Jan. 25 to market the drug for children newly diagnosed with Philadelphia chromosome positive acute lymphoblastic leukemia.

Acute lymphoblastic leukemia is the most common cancer in children, representing about 23 percent of pediatric diagnoses, according to the National Cancer Institute. About 2,900 children and adolescents younger than 20 years old in the U.S. are diagnosed with the disease each year, which causes unformed blood cells and peaks among 2- to 3-year-olds.

High Price

Before Gleevec, the recommended treatment for the disease was a bone marrow transplant, Reaman said.

Many cancer treatments used now were developed at least two decades ago, Peter Adamson, chief of the division of clinical pharmacology and therapeutics at the Children’s Hospital of Philadelphia, said. Adamson also serves as chairman of the Children’s Oncology Group, which helps coordinate most pediatric clinical trials in cancer.

“The price children are paying is too high,” Adamson said in a telephone interview. “And the price is side effects during treatment and perhaps more importantly life-long effects.”

More than 80 percent of pediatric patients experience severe, life-threatening or fatal toxicities, mainly infections, from cancer treatment, he said. About 40 percent of survivors experience side effects that affect their daily lives, including heart failure, hearing loss and learning disabilities.

Europe particularly needs to change its regulatory environment, according to the series of articles. The EU’s Clinical Trials Directive implemented in 2004 requires pediatric research of drugmakers that request marketing approval for their products yet made the requirements onerous when perhaps such data might not exist, Reaman said.

Unsustainable Funding

The directive quadrupled development costs and can lead to substantial approval delays, according to the articles. Adamson and Reaman each worked on parts of the Lancet Oncology series.

Novel drug development for children suffering from cancer needs public-private partnerships since drugmakers aren’t highly incentivized to enter the small market, Reaman said.

“The continuation and advancement of research into children with cancer depends on long-term, sustainable funding; however, evidence suggests that pediatric research and development is reliant on short-term unsustainable funding,” the doctors wrote in the article series.

The FDA in the U.S. is working to advance research and coordination. The agency has responded to one of the companies that received scrutiny at the December meeting of pediatric advisers to help them expand and improve upon a proposed children’s study, Reaman said. He didn’t say which company.

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