There is a Phase II monotherapy abstract:
[385] A Phase II Multicenter Study of the Proteasome Inhibitor Bortezomib (VELCADE™, Formerly PS-341) in Multiple Myeloma Patients (pts) with Relapsed/Refractory Disease.
Paul Richardson, Bart Barlogie, James Berenson, Ann Traynor, Seema Singhal, Sundar Jagannath, David Irwin, Vincent Rajkumar, Gordon Srkalovic, Melissa Alsina, Raymond Alexanian, David Siegel, Robert Z. Orlowski, David Kuter, Steven A. Limentani, Stephanie Lee, Dixie-Lee Esseltine, Michael Kauffman, Julian Adams, David P. Schenkein, Kenneth C. Anderson. Dana-Farber Cancer Institute, Boston, MA, USA; University of Arkansas, Little Rock, AR, USA; Cedars-Sinai Medical Center, Los Angeles, CA, USA; Northwestern University Medical Center, Chicago, IL, USA; St. Vincent's Catholic Medical Center, New York, NY, USA; Alta Bates Comprehensive Cancer Center, Berkeley, CA, USA; Mayo Clinic, Rochester, MN, USA; Cleveland Clinic Foundation, Cleveland, OH, USA; H. Lee Moffitt Cancer Center, Tampa, FL, USA; M.D. Anderson Cancer Center, Houston, TX, USA; Carol G. Simon Cancer Center, Morristown, NJ, USA; University of North Carolina, Chapel Hill, NC, USA; Massachusetts General Hospital, Boston, MA, USA; Charlotte Medical Clinic, Charlotte, NC, USA; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA
Proteasome inhibition represents a novel potential pathway for targeted anticancer therapy. Bortezomib (VELCADE™, formerly PS-341), a potent and selective inhibitor of the proteasome, is a first-in-class small molecule that in preclinical studies has shown numerous effects on regulatory proteins, including the blockade of NF-kB activation. We have completed the treatment phase of a study of bortezomib in pts with advanced relapsed/refractory multiple myeloma. Pts received bortezomib at 1.3 mg/m2 by IV push on Days 1, 4, 8, and 11 of a 21-day cycle for up to 8 cycles. Addition of dexamethasone was permitted in pts with progressive disease after 2 cycles or stable disease after 4 cycles. The primary objective was response rate. Response was determined by an independent response committee (IRC) using stringent Blade criteria. Two hundred two pts were enrolled in 2 cohorts (n = 78 and 124). Pts in cohort 1 (78 pts) had a mean of 5 prior lines of therapy (range 2–14) and were a median of 4 years from diagnosis. Seventy-four percent had previously received thalidomide; 54% had received high-dose therapy. Based on the IRC review of response to bortezomib alone (ie, before dexamethasone was allowed) in cohort 1, the overall response rate was 32% (CR, PR, MR). Twenty-seven percent had major responses (4% CR, 23% PR), with 9% of the PR pts meeting all criteria for CR with the exception of negative immunofixation (designated near CR). Therefore, the CR and near-CR rate was 13%. By analysis of change in paraprotein only, 68% of pts had either decreased or stable paraprotein levels. The median duration of response in CR/PR pts has not been reached at 10.2 months (median) of follow-up. Responding pts showed evidence of improved hemoglobin, performance status, quality-of-life, and levels of non-M protein immunoglobulins. The median survival for cohort 1 has not been reached (median follow-up 10.2 months, range 1.4+ to 16.7+ months). Efficacy and safety data, including an analysis of the contribution of added dexamethasone, will be presented for both cohorts (202 patients). In this trial, response rate was associated with clinical benefit for pts with relapsed/refractory myeloma progressing on last therapy. Bortezomib represents a novel potential approach to the treatment of pts with relapsed/refractory multiple myeloma.
Keywords: Proteasome inhibitor\ Myeloma\ PS-341
Those are good numbers in this difficult population - be interesting to see what they report about the combo w/
dexamethasone.
(Note I didn't see anything about an embargo on the site, so I went ahead and posted this here).
Peter |
