ROCKVILLE, Md--After hours of heated debate, the FDA's Oncologic
Drugs Advisory Committee (ODAC) decided there was sufficient evidence
of efficacy to recommend approval of DOX-SL (pegylated liposomal
doxorubicin) for the treatment of AIDS-related Kaposi's sarcoma
(KS) in patients who have failed first-line treatment or who cannot
tolerate other treatment. The potential benefits of the drug generally
outweigh the risks, the committee said.
However, their recommendation to the FDA was for accelerated approval
of the drug. A recommendation for unconditional approval was unanimously
voted down, due to concerns about possible protocol and safety
violations and difficulties in measuring improvements in the studies.
Under the accelerated approval status, the drug's sponsor, Liposome
Technology, Inc. (LTI), of Menlo Park, Calif, will be required
to collect additional pertinent data to carry out appropriate
'Not Just Another Analog'
I. Craig Henderson, MD, chief of medical oncology, University
of California, San Francisco, and a director of LTI, referred
to DOX-SL as a "new drug" rather than an analog of doxorubicin.
He said that liposomes are generally versatile drug carriers,
but they may be limited in their ability to reach target cells.
However, DOX-SL, a liposome packed with doxorubicin, has proved
to be highly stable, with a relatively long half-life and clearance
Because of its long plasma residence time, DOX-SL tends to preferentially
enter tissues with compromised blood vessels (such as soft-tissue
tumors) and therefore provides good therapeutic effect, Dr. Henderson
said. In a regimen of 20 mg/m² every 3 weeks, DOX-SL has
demonstrated the ability to deliver and maintain therapeutic doses
of doxorubicin to KS lesions.