Paraprotein level response and major response are not the some. However paraprotein level seams does correlate with TTP (achieving stable disease is still success if there is additional medical benefit) and survival.
How many pts added (not moved) DEX to Velcade? I think that good portion of pts did already tried DEX (marketed as second line therapy), alone or in some other combinations and progressed??? So, adding DEX after progression or stabilization on Velcade is sound and prudent.
BTW, data on response, TTP and survival are only for first cohort.
To me interesting and of more value is second PII trial. However, I thought that this trial enrolled ~200 pts, not 54 as MLNM reported in abstract???? :(
This may change my thought on time to NDA file.
[3207] A Phase II Multicenter Randomized Study of the Proteasome Inhibitor Bortezomib (VELCADE™, Formerly PS-341) in Multiple Myeloma (MM) Patients (pts) Relapsed after Front-Line Therapy.
Sundar Jagannath, Bart Barlogie, James Berenson, David Siegel, David Irwin, Paul G. Richardson, Raymond Alexanian, Steven A. Limentani, Melissa Alsina, Stephanie Lee, Dixie-Lee Esseltine, Michael Kauffman, Julian Adams, David P. Schenkein, Kenneth C. Anderson. St. Vincent's Catholic Medical Center, New York, NY, USA; University of Arkansas, Little Rock, AR, USA; Cedars-Sinai Medical Center, Los Angeles, CA, USA; Carol G. Simon Cancer Center, Morristown, NJ, USA; Alta Bates Comprehensive Cancer Center, Berkeley, CA, USA; Dana-Farber Cancer Institute, Boston, MA, USA; M.D. Anderson Cancer Center, Houston, TX, USA; Charlotte Medical Clinic, Charlotte, NC, USA; H. Lee Moffitt Cancer Center, Tampa, FL, 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. Multiple myeloma demonstrates a strong dependency on NF-kB and NF-kB–dependent genes as growth factors and for adhesion of plasma cells in the bone marrow (IL-6, VEGF, VCAM-1). In a large (202 pts) phase II clinical trial in myeloma patients with relapsed and refractory disease, this drug had an overall response rate of 32% (CR, PR, MR). Here, we present the results of a study of 2 doses of bortezomib in patients with earlier stage disease (relapsed or refractory multiple myeloma after front-line therapy). Eligible patients had either progressed on front-line therapy or relapsed at any time after front-line therapy. Patients were randomized to receive either 1.0 mg/m2 or 1.3 mg/m2 bortezomib 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 patients with progressive or stable disease after 2 and 4 cycles, respectively. The primary objective was response rate. Response was determined using the stringent Blade criteria and verified by an independent response committee (IRC). Fifty-four patients were enrolled and treated with bortezomib at either 1.0 mg/m2 or 1.3 mg/m2. Enrollment and treatment have been completed at this time. Efficacy and safety data will be presented for both dose groups. Bortezomib represents a novel potential approach to the treatment of patients with relapsed or refractory multiple myeloma.
Keywords: Proteasome inhibitor\ Myeloma\ PS-341 |
