Home Run for Pediatric Cancer Drug

Childhood cancers respond to Xalkori in phase I trial

/ Author:  / Reviewed by: Chris Galloway, M.D.

(RxWiki News) An early study looking at a treatment for cancers involving a certain gene mutation had better results than expected, with findings showing that no traces of cancer are detectable in some of the patients in the drug trial.

The first phase of clinical trials on Xalkori (crizotinib) performed well in three childhood cancers with a mutation in the ALK gene, including anaplastic large cell lymphoma, neuroblastoma, and inflammatory myofibroblastic tumors.

"Ask your doctor about the latest clinical trials available for your cancer."

While Xalkori is FDA-approved for the treatment of ALK positive advanced non-small cell lung cancer, this is the first clinical trial testing the drug in children. Larger trials will soon follow this initial step now that dosages and toxicity have been established in the first phase of testing.

If these kinds of results hold, Xalkori could become a main therapy in treating childhood cancers involving ALK mutations.

Unfortunately, treatment with Xalkori is not effective in all cases of these cancers, as genetic abnormalities in the ALK gene only show up in 80 percent of anaplastic large cell lymphomas, around half of inflammatory myofibroblastic tumors, and only 10 percent of neuroblastomas.

Children entered in the drug trial had not responded to any of the standard therapies currently available. Varying doses of Xalkori were to the 70 children in the trial in order to determine appropriate dosing for the next phase of testing.

  • Seven of the eight patients with anaplastic large cell lymphoma had a complete response to treatment, with no cancer detectable as of publication, 18 months after the trial concluded.
  • Out of the seven patients with inflammatory myofibroblastic tumors, results varied from tumor shrinkage to complete regression with no resistance developing even two years after therapy began.
  • Out of the eight patients with an identified ALK mutation, two had a complete response, and as of publication have two years of therapy without progression. Researchers stated that the best results from similar trials on other drugs showed treatment failure after only two months. 

Results for the neuroblastoma patients were not as encouraging. Researchers identified two problems they will work on correcting in future phases of the drug trial. 

First of all, screening for the ALK mutation was not required for entering the trial, and higher doses of Xalkori are necessary for effective treatment for neuroblastoma. These findings will be taken into account for the next two phases of drug testing.

While the clinical trial has only completed the first phase, traditionally an initial evaluation of toxicity and dosage, researchers were very enthusiastic about the results demonstrated so far.

“It’s remarkable that this targeted oral medication provided such a substantial benefit in these children with highly aggressive cancers, most of whom had already undergone every available therapy,” stated the study's lead author, Yael Mosse, MD from the University of Pennsylvania.

“Now that we know more about the drivers of some pediatric cancers, we can target those changes and treat patients in a much smarter, and potentially safer, way.”

Findings from this study were presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO)

Research presented at conferences is considered preliminary until publication in a peer-reviewed journal.

Study funding was provided by Pfizer, the manufacturer of Xalkori.

Reviewed by: 
Review Date: 
June 2, 2012
Last Updated:
June 5, 2012