(Reuters) – Phase I study results suggest that Pfizer Inc’s lung cancer drug crizotinib (Xalkori) may be a highly effective treatment for children with a rare but aggressive type of lymphoma and other cancers, according to data from an early stage study released on Wednesday.
Crizotinib is approved to treat non-small cell lung cancer in patients with a specific mutation in the anaplastic lymphoma kinase (ALK) gene. But some patients with other types of cancer have also been found to have abnormal ALK.
The study included 70 children whose various cancers had progressed despite standard therapies. Determining the safety of crizotinib in children was the primary goal of the phase I study that tested the drug at several doses.
The trial, however, was not restricted to patients with known ALK abnormalities and was open to those with certain cancers that had relapsed or did not respond to other treatments, researchers said. Going forward, further studies will include only children with the ALK mutations, researchers say.
Of the 57 children in the study who could be fully evaluated for drug toxicity, toxic side effects were deemed to be minimal, even though many of the crizotinib doses tested were relatively high, according to a statement issued by the study team.
“The drug was exceedingly well-tolerated. Most toxicities were extremely low grade and did not impact quality of life,” Dr. Yael Mosse, the study’s lead researcher from the Children’s Hospital of Philadelphia, told reporters on a conference call.
The studied doses ranged from 100 mg to 365 mg, taken twice a day for 28-day cycles. Based on the study findings, researchers determined that the recommended dose for children in future studies will be 280 mg, roughly twice the adult-recommended dose.
The data will be presented at next month’s ASCO meeting in Chicago, but were released on Wednesday along with summaries of hundreds of other studies that will be featured at the year’s most important cancer meeting.
Eight children in the study were suffering from anaplastic large cell lymphoma (ALCL), and seven of the eight had a complete response to the drug, with follow-up of up to 18 months.
The study also tested crizotinib in 27 children with neuroblastoma and in seven children with inflammatory myofibroblastic tumors (IMT).
Two of the neuroblastoma patients had a complete remission and eight had stable disease. The most demonstrable response in neuroblastoma was seen at the higher doses, researchers said. “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,” the research team said in a statement.
The majority of the seven IMT patients experienced substantial benefit, ranging from tumor shrinkage to complete tumor regression, researchers found. These responses have lasted up to two years so far. No other available anticancer therapies are effective in this disease, according to the investigators.
Dr. Michael Link, president of the American Society of Clinical Oncology (ASCO) and a pediatric oncologist, characterized the response rates as “pretty phenomenal.” He was not involved in the research.
“The durability of the response is pretty amazing,” he said.
“In ALCL this is dramatic activity. In neuroblastoma there’s still a lot of work to be done to identify the patients likely to benefit,” Dr. Mosse said.