How to beat childhood cancer

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How to beat childhood cancer

For a parent, there is perhaps no greater fear than the prospect of losing a child to illness or accident. And it is childhood cancer that has the greatest potential to catapult a remote fear into an unimaginable reality. As a pediatric oncologist, having cared for children with cancer and their families for more than 25 years, I know that only a parent who has confronted such a diagnosis truly understands the depth of this fear, as it touches the core of who we are as parents.

I also know that we are treating more children more effectively than ever before - and that we can do much better still.

For a child born in the 1960s, the diagnosis of the most common form of childhood cancer, acute lymphoblastic leukemia (ALL), meant almost certain death, with a survival rate of less than 10 percent.

A child with the same diagnosis today has a better than 80 percent chance of being cured. Looking at the five-year survival rates for children with ALL from the 1970s through the ’90s, one sees an almost linear improvement in cure rates.

This makes the ’70s, ’80s and ’90s look like an era of accelerating discovery and therapeutic development. But virtually all of the drugs that we use today to cure children with cancer were discovered and approved in the ’50s and ’60s. So, if new drugs did not fuel four decades of progress, what did?

A major driver was a remarkable, sustained scientific collaboration. In the 1950s, a group of clinical scientists recognized that, because childhood cancer was a rare disease, no single medical center could study enough patients to make the necessary advances across the spectrum of pediatric oncologic diseases. The decision to conduct collaborative research across multiple institutions resulted in the development of cooperative group research.

In the fight against childhood cancer, this concept evolved into what is now the Children’s Oncology Group (COG), which unites more than 8,000 experts at more than 200 leading children’s hospitals, universities, and cancer centers across North America, Australia, New Zealand, and parts of Europe. The COG conducts research across the spectrum of cancers that afflict children, and has approximately 100 clinical trials underway around the world.

With an emerging infrastructure in place for cooperative research, sustained improvement in outcomes partly reflected an ever-increasing understanding that childhood cancers are diverse. Childhood ALL, for example, is not a single disease, but rather a spectrum of diseases. Recognition of this diversity led to the study of different treatment regimens in different sub-populations of children with pathologically similar cancers.

Throughout this period, the ability to overcome the most common side effect of cancer drugs, myelosuppression (a decrease in blood counts), improved dramatically. It began with the ability to transfuse not only red blood cells into anemic patients, but also platelets, reducing the threat of life-threatening bleeding that can accompany cancer therapy.

Equally important, the risks and types of life-threatening infections that come with myelosuppression were increasingly recognized, leading to the development and better use of more effective antibiotics. Starting in the 1990s, cytokines, drugs that stimulate bone marrow to produce infection-fighting white blood cells, began to be integrated into cancer treatments, further mitigating the risk of life-threatening infectious complications of care.

As a result of these advances in science and supportive care, the same chemotherapeutic drugs could be delivered much more intensively for children with select types and subtypes of cancer. With selective intensification, cure rates began to increase steadily.

And yet, while this strategy has indeed resulted in better outcomes, the acute and long-term morbidity of therapy has been substantial. Children with high-risk cancers who receive dose-intensive chemotherapy have a greater than 80 percent chance of experiencing at least one severe, life-threatening, or fatal drug-related toxic event over the course of their treatment.

The late effects of cancer treatment include permanent organ and tissue damage, hormonal and reproductive dysfunction, and second cancers. More than 40 percent of the estimated 330,000 survivors of childhood cancer in the United States experience a significant health-related complication from childhood cancer and its treatment. And, despite our advances, cancer in developed countries remains the leading cause of death from disease in children older than one year.

We are, however, entering an era of unprecedented discovery. The powerful research tools that we now have to uncover the underlying basis of childhood cancers could fundamentally change how we treat children with these dreaded diseases. For a limited number of childhood cancers, there are new drugs that can target the fundamental drivers of malignancy. The most notable example is the impact of Gleevec (imatinib mesylate) on outcomes for children with an uncommon subtype of leukemia - Philadelphia chromosome-positive ALL.

The addition of this inhibitor to intensive chemotherapy has dramatically improved the outlook for these children, increasing the rate of three-year event-free survival from 35 to 80 percent. The development of targeted new agents is likely to affect outcomes for other subtypes of childhood cancer, including anaplastic large-cell lymphoma and other types of leukemias.

Given that childhood cancers are all rare or ultra-rare diseases, the ability of the biopharmaceutical industry to invest resources into development of new treatments is limited at best. Yet research is needed to identify potential targets for the entire spectrum of childhood cancers. For some potential targets, public-private partnerships will be needed to develop new therapeutic approaches.

The past 40 years have demonstrated the remarkable return on investment to be gained in collaborative scientific research. Now we must leverage current scientific opportunities and invest the resources needed to develop more effective, less toxic therapies, thereby improving outcomes for all children with cancer.

Copyright: Project Syndicate, 2013

*The author is chair of the children’s oncology group at The Children’s Hospital of Philadelphia.

by Peter C. Adamson
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