CHICAGOEight out of nine patients with advanced multiple myeloma
responded to LDP-341, a proteasome inhibitor formerly called PS-341, during a
phase I clinical trial in patients with advanced hematologic malignancies,
according to preliminary results reported at the American Chemical Society’s
The announcement by Robert Orlowski, MD, of the Lineberger Comprehensive
Cancer Center, University of North Carolina at Chapel Hill, was so upbeatone
woman had a complete responsethat by October 2001, a multicenter phase II
trial of LDP-341 in multiple myeloma reached full enrollment ahead of schedule.
Dr. Orlowski also reported partial responses in two patients with non-Hodgkin’s
lymphoma who had been enrolled in the phase I study.
"To have this number of responses, even if partial, and to have any
complete responses, is very unusual and very encouraging," Dr. Orlowski
told ONI. He noted that the phase I study was supported in part by the Leukemia
and Lymphoma Society.
The drug’s developer, Millennium Pharmaceuticals, Inc., Cambridge,
Massachusetts, has also initiated a phase II trial of LDP-341 in patients with
chronic lymphocytic leukemia (CLL) and phase I trials in conjunction with
chemotherapy agents for solid tumors.
While multiple myeloma patients have had the best results to date, Julian
Adams, PhD, senior vice president for drug discovery at Millennium, said that
the company was encouraged by early work with solid tumors, particularly
prostate, lung, colon, breast, and pancreatic cancers.
"The LDP-341 trials are the first time a proteasome inhibitor has been
used in humans in any type of disease, and it is uniquely designed to work in
cancer," he told ONI. It has been well tolerated in about 200 patients
treated to date, he said.
Proteasome inhibitors block an enzyme that degrades unwanted proteins tagged
with ubiquitin. Blocking the enzyme causes these proteins to accumulate in the
cell, interfering with normal function and promoting cell death. Apoptosis also
appears to be advanced by interference with cellular signaling.