GAITHERSBURG, Md--An FDA advisory panel has recommended approval
of Guilford Pharmaceutical's Gliadel Wafer (polifeprosan 20 with
carmustine) for use as an adjunct to surgery to prolong survival
in recurrent glioblastoma multiforme (GBM).
The Oncologic Drugs Advisory Committee (ODAC), however, urged
that FDA approve the use of the drug delivery system only for
GBM patients until further study resolves efficacy issues.
The Gliadel system consists of a wafer containing polifeprosan
20, a biodegradable, polyanhydride co-polymer, and carmustine
(BiCNU), said Ross S. Laderman, Guilford's vice president for
regulatory affairs. About dime-size in diameter, the wafers measure
1 mm thick. Up to eight wafers, and almost always a minimum of
seven, are placed in the brain cavity created by the tumor's removal.
The wafers release most of their car-mustine within a few days.
About 50% is released in 3 days and "greater than 80% is
released within 7 days after wafer implantation," said Dr.
Craig R. Smith, Guilford's CEO. "Tumoricidal concentrations
have been found adjacent to the wafers up to 21 days after implantation."
Dr. Earl Webb Henry, Guilford's vice president for clinical research,
reviewed two phase III randomized, controlled, double-blind Gliadel
trials. Study 8802 involved 222 patients undergoing surgery for
recurrent malignant glioma. The primary endpoint for this US-Canadian
study was 6-month survival.
Study CL-0190, which used 12-month survival as its primary endpoint,
was carried out in Finland and Norway. Its protocol called for
up to 100 patients undergoing initial surgical resection for malignant
glioma. But because of an inadequate supply of wafers, researchers
enrolled only 32.
In trial 8802, 110 patients received carmustine-containing wafers
and 112 got drugless wafers. "At 6 months, 60% of all Gliadel
patients and 47% of all placebo patients were still alive,"
Dr. Henry said. "The survival difference was at the margin
of significance (P = .06)." Gliadel patients showed an early
survival benefit, "but nearly all of this was within the
first 12 months," he noted.