Experimental Drug Helps Fight Some Childhood Cancers, Study FindsLast Updated: May 16, 2012. Targeted therapy is effective, has few side effects, but larger trials needed, researchers say.
By Serena Gordon
WEDNESDAY, May 16 (HealthDay News) -- A new targeted drug therapy may help treat certain advanced cancers in children, a new preliminary study indicates.
In some cases, the oral medication even made tumors disappear after regular cancer treatments had failed, the researchers reported.
"This is an exciting first step, and it looks very promising for kids who have had very few options," said study author Dr. Yael Mosse, an assistant professor of pediatrics in the division of oncology at Children's Hospital of Philadelphia.
Mosse is scheduled to present the findings on June 2 at the American Society of Clinical Oncology (ASCO) meeting in Chicago. However, ASCO released the results during a news conference Wednesday. Funding for the study was provided by the drug's manufacturer, Pfizer Inc.
The new drug is called crizotinib (Xalkori), and it targets abnormalities in a gene called ALK that's present in certain cancers. The drug was recently approved by the U.S. Food and Drug Administration for treating adult lung cancers caused by an ALK defect.
ALK is not "expressed" -- or produced -- in healthy individuals. Only cancer cells express ALK, according to Mosse. "ALK is there to promote growth of cancer cells," she explained. That means any treatment that blocks ALK will only affect cancer cells and not healthy ones.
"Healthy cells don't recognize this drug. It's much different than chemotherapy," Mosse said.
The three types of pediatric cancers currently targeted for this drug therapy include anaplastic large cell lymphoma (ALCL), a type of blood cancer; neuroblastoma, a nerve cancer that usually affects the adrenal gland or the chest; and inflammatory myofibroblastic tumors (IMT), which often causes tumors to develop in muscle.
ALK genetic abnormalities are found in between 80 percent and 95 percent of anaplastic large cell lymphoma cancers, about half of inflammatory myofibroblastic tumors, and between 10 percent and 15 percent of aggressive neuroblastomas.
The new study was a phase 1 study, which means it was designed only to assess the safety of the medication, not its effectiveness.
The initial safety study had 70 patients with one of the three ALK-driven cancers. Mosse said the drug was extremely well-tolerated, with mostly mild side effects, such as diarrhea or nausea. She said some children had mild vision changes, but there was no significant effect on sight, and some children had changes in the results of liver function tests.
Although the study wasn't designed to measure the drug's effectiveness, its benefits quickly became apparent, especially for anaplastic large cell lymphoma cancers. Eighty-eight percent (seven out of eight children with an ALK abnormality) had a complete response to the drug, and now have no detectable disease. At this point, the study volunteers have been on the drug for as long as 18 months, the researchers noted.
Seven children with inflammatory myofibroblastic tumors were enrolled in the trial, and the majority have had either tumor shrinkage or complete tumor regression. Said Mosse: "Right now, the only effective way to cure this type of cancer is to remove it surgically. If you can't remove it all, it comes back. Our first patient had a tumor in the shoulder and amputating the entire arm was the only cure possibility they were given. We gave this patient a very low dose and saw a dramatic benefit of the drug."
Neuroblastomas are proving to be more of a challenge. The researchers found two of 27 study volunteers showed complete tumor regression. Eight have had no disease progression. Giving higher doses of crizotinib seemed to be more effective, and it was still well-tolerated.
Mosse said the drug will go to phase 2 testing for neuroblastomas so researchers can try to distinguish who might respond best to the drug. The researchers also want to know how effective this drug might be if given early in the course of a cancer, and how well would it work in combination with chemotherapy.
As with most cancer drugs, Mosse said there's a concern that these cancers may eventually develop a resistance to this medication. However, the researchers haven't seen evidence of that yet.
Dr. Rosanna Ricafort, clinical director of the pediatric blood and marrow transplant program at the Children's Hospital at Montefiore Medical Center in New York City, said, "This is an emerging paradigm in oncology -- we can achieve clinical efficacy with molecularly targeted therapies."
"We need to confirm the efficacy of crizotinib in larger studies, but these findings are very exciting. It was fortunate that crizotinib was already available for adult cancers," she added.
Ricafort said that parents who have a child with one of these cancers should ask their oncologist if their child should be tested for an ALK abnormality because of the potential treatment options. She said she doesn't think the drug will be available outside of a clinical trial for some time.
Mosse agreed that parents should have a discussion about whether their child's cancer should be screened for ALK abnormalities. She added that tumor samples likely need to be sent to Children's Hospital of Philadelphia, as it may be the only site doing the test right now.
Research presented at medical meetings should be viewed as preliminary until published in a peer-reviewed medical journal.
Learn more about crizotinib at the U.S. National Cancer Institute.
SOURCES: Yael Mosse, M.D., assistant professor, pediatrics, division of oncology, The Children's Hospital of Philadelphia; Rosanna Ricafort, M.D., clinical director, pediatric blood and marrow transplant program, The Children's Hospital at Montefiore, New York City; June 2, 2012, presentation, American Society of Clinical Oncology annual meeting, Chicago