GAITHERSBURG, Md--Members of the FDA's Oncology Drug Advisory
Committee (ODAC) agreed that Immu-nex Corp.'s Novantrone (mitoxan-trone)--in
combination with corticosteroids--offers a clinical benefit to
patients with hormone-resistant prostate cancer.
However, the panel recommended further evaluation of trial data
before the FDA makes a decision. Novantrone was originally approved
in 1987 for use in acute myelogenous leukemia.
"Until recently, we have had no effective chemotherapy for
advanced prostate cancer," said Ian Tannock, MD, professor
of medicine at the University of Toronto, who led the pivotal
study of the drug. "Pain is the dominant problem."
At the meeting, the company presented data from two unblinded
clinical trials to back up its contention that the drug combination
decreases pain, suppresses prostate cancer, and significantly
improves quality of life in advanced disease patients.
The pivotal study of the drug's analgesic effects involved 161
patients treated at 11 centers with Novantrone plus pred-nisone
or prednisone alone. Its primary endpoint called for a reduction
of two points on a six-point pain scale with stable analgesic
Of 80 patients receiving the combination, 21 (26%) achieved this
endpoint, as did 10 (12%) of the 81 patients given prednisone
only. Those getting the drug combination had a median time to
progression of 168 days, compared with 62 days in the prednisone-only
group. PSA was reduced in 27% of patients who received the combination,
compared with 5% of patients in the prednisone-only group. There
was no significant difference in median survival (339 vs 324 days).
A supportive study involved 119 prostate cancer patients given
Novantrone plus hydrocortisone and 123 given hydrocortisone alone
at 62 centers. This study did not examine the primary endpoint
of the first study, but did find a PSA decrease in 14% of patients
and a time to progression of 218 days in the Novantrone-hydrocortisone
group versus a PSA drop in 5% of patients and a progression time
of 122 days for those getting hydrocortisone only.