進行性小児がん治療に関する有望な結果（Abstract # 9500）

A Phase I study presented at the American Society of Clinical Oncology's 48th Annual Meeting has shown that the targeted drug crizotinib stalled tumor growth and, in some cases, eradicated all signs of cancer in select children with aggressive forms of neuroblastoma, anaplastic large cell lymphoma (ALCL) or inflammatory myofibroblastic tumors (IMT). 

Crizotinib targets genetic abnormalities in the ALK gene, which are common in these pediatric cancers. If these promising early-phase findings are borne out in larger trials, crizotinib could become only the second effective molecularly targeted therapy for pediatric cancers. ALK abnormalities are present in 80 to 95 percent of ALCL cases, half of IMTs and 10 to 15 percent of aggressive neuroblastomas. Crizotinib was recently approved in the United States to treat adult ALK-driven lung cancers, about 5 percent of cases.

"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," said Yael Mosse, M.D., assistant professor of pediatrics at the Children's Hospital of Philadelphia and 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."

The study included 70 children whose cancer had progressed despite all standard therapies. When possible, patients' cancers were tested for ALK abnormalities, though this was not required for enrollment. Patients received one of six different doses of crizotinib – administered orally, twice a day – and remained on the drug as long as it was well-tolerated, which was the case in the vast majority of patients. By disease, researchers found:

• ALCL: 88 percent (7/8) of patients experienced a complete response, having no detectable disease. Responses have been long lasting, with patients remaining on treatment with no progression for as long as 18 months.
• IMTs: Seven patients with this rare disease were enrolled onto this trial. The majority have experienced substantial benefit, ranging from tumor shrinkage to complete tumor regression. Such responses have lasted for up to two years, with all patients still receiving therapy; these findings are important because no other available anticancer therapies are effective in this disease.
• Neuroblastoma: Overall, two of 27 patients had a complete response, and eight have had no disease progression (stable disease). Of patients with a proven ALK abnormality, two of eight patients experienced a complete response. These responders have remained on therapy for between 9 months to more than two years without progression – a notable finding given that most heavily pre-treated neuroblastoma patients on a Phase I trial experience cancer progression in 1 to 2 months.

Researchers also observed that neuroblastoma patients treated with higher doses of crizotinib – which in some cases were twice the approved adult dose – experienced demonstrable responses. This may explain why some neuroblastoma patients with proven ALK abnormalities did not respond to crizotinib, since they had received lower doses of the drug than the responders.

Dr. Mosse is the recipient of this year's James B. Nachman ASCO Junior Faculty Award in Pediatric Oncology.