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Biotech / Medical : Millennium Pharmaceuticals, Inc. (MLNM) -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (2117)	5/25/2004 3:52:30 PM
From: tuck	Respond to of 3044

[Phase I Study of Bortezomib in Refractory or Relapsed Acute Leukemias ] >>Clinical Cancer Research Vol. 10, 3371-3376, May 15, 2004 Clinical Trials Phase I Study of Bortezomib in Refractory or Relapsed Acute Leukemias Jorge Cortes1, Deborah Thomas1, Charles Koller1, Francis Giles1, Elihu Estey1, Stefan Faderl1, Guillermo Garcia-Manero1, David McConkey2, Gira Patel2, Roberto Guerciolini3, John Wright4 and Hagop Kantarjian1 Departments of 1 Leukemia and 2 Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; 3 Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts; and; 4 Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland Bortezomib (Velcade, formerly PS-341) is proteasome inhibitor with documented antitumor activity in multiple myeloma and other lymphoid malignancies. We performed a Phase I study to investigate the maximum tolerated dose and dose-limiting toxicity of bortezomib in patients with acute leukemias refractory to or relapsing after prior therapy. Fifteen patients were treated with 0.75 (n = 3), 1.25 (n = 7), or 1.5 (n = 5) mg/m2 bortezomib administered twice weekly for 4 weeks every 6 weeks. Dose-limiting toxicity included orthostatic hypotension (n = 2), nausea (n = 2), diarrhea (n = 1), and fluid retention (n = 1), all at 1.5 mg/m2 bortezomib. Proteasome inhibition was dose dependent and reached 68% at 1.5 mg/m2 bortezomib. Peak inhibition was observed 1 h after treatment and returned to near baseline levels by 72 h after treatment. Incubation of blast cells with bortezomib in vitro showed induction of apoptosis in three of five patients investigated. We conclude that the maximum tolerated dose of bortezomib in patients with acute leukemia is 1.25 mg/m2, using a twice-weekly for 4 weeks every 6 weeks schedule. The in vitro evidence of antileukemia and transient hematological improvements observed in some patients warrants further investigation of bortezomib in acute leukemias, probably in combination with other agents.<< Some dosing clues here. Have we seen other studies with bortezomib in this population? I haven't the time to check. Cheers, Tuck