Febrile Neutropenia Test Of Cure Visit Timing Should Be Reassessed - Cmte.

FDA should consider shortening the time to test-of-cure visit in trials of empiric antibiotic therapies for febrile neutropenia, FDA's Anti-Infective Drugs Advisory Committee recommended July 31.

"If we wait seven days to evaluate, what often happens is the patient becomes febrile again and you can't assess what it's due to," said committee member Carl Norden, MD, Cooper Hospital. "Then you get into the real difficulty of what you say was the outcome or the response of the initial course of therapy."

The FDA draft guidance for the development of antimicrobial drugs for the treatment of febrile neutropenia recommends a test-of-cure visit "at least seven days after completion of therapy."

"If the patient is no longer neutropenic, I have no problem looking at [TOC] out at a little longer," Committee Chairman William Craig, MD, University of Wisconsin, commented. "On the other hand, if you're stopping therapy when the patient is still neutropenic, and you're looking at the seven days while they're still neutropenic...there's going to be a good likelihood that you're going to see a relapse.

In reassessing timing of the TOC visit, FDA should redefine end of therapy, committee member Patricia Chesney, MD, University of Tennessee College of Medicine, suggested. The draft guidance recommends treatment for at least seven days after defeverfesence or until neutropenia has resolved.

"I think the end result is stratified by whether or not the white cells are present or not present," Chesney said. "You can't talk about test-of-cure at seven days when you don't clearly define when you can end therapy without taking into account what the white cells are."

The most common endpoint in febrile neutropenia trials has been return of white blood cells, committee member Barth Reller, MD, Duke University Medical Center noted. "I think it might be better to define reasonable assessment points based on objective events that happen to do with temperature or white cell return," he stated.

Reller suggested changing the timing of assessments to look at some period after defervescence, return of white blood cells above a set number, and a seven day test-of-cure visit based on a more specific endpoint of therapy.