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(1165) Tanespimycin (T) + Bortezomib (BZ) in Multiple Myeloma (MM): Confirmation of the Recommended Dose Using a Novel Formulation. Session Type: Poster Session, Board #319-I

(1165) Tanespimycin (T) + Bortezomib (BZ) in Multiple Myeloma (MM): Confirmation of the Recommended Dose Using a Novel Formulation. Session Type: Post

(1165) Tanespimycin (T) + Bortezomib (BZ) in Multiple Myeloma (MM): Confirmation of the Recommended Dose Using a Novel Formulation. Session Type: Poster Session, Board #319-I  
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Paul G. Richardson, Asher Chanan-Khan, Sagar Lonial, Amrita Krishman, Michael Carroll, G. F. Cropp, K. Kersey, M. Abitar, R. G. Johnson, Alison L. Hannah, Kenneth C. Anderson, Dana Farberhttp://academic.research.microsoft.com/io.ashx?type=5&id=14146944&selfId1=0&selfId2=0&maxNumber=12&query=
were enrolled in 7 cohorts (T 100- 340 mg/m2; BZ 0.7 1.3 mg/m2). Confirmation of the phase 2 dose occurred in 27 pts across 2 groups: 1 group received a Cremophor formulation; a 2nd group received a suspension formulation without steroid premedication (n=13 and 14 pts, respectively). Results: The recommended phase 2 dose equals T 340 / BZ 1.3 mg/m2. At this dose (n=26), common all-grade (G) drug- related toxicity in pts included diarrhea (39%), dizziness (27%), nausea (23%), AST (23%), vomiting (23%), fatigue, ALT and peripheral edema (all 19%). No difference in toxicity was seen between the 2 formulations, consistent with the clinical experience to date using the suspension product (n=31). G3 and G4 thrombocytopenia was noted in 15% and 12%; no other G3 toxicity was observed in more than 1 pt. No G3 neurotoxicity was seen at any dose. For the Cremophor (n=18) and suspension formulation (n=12), AUC (parent+metabolite) equaled 30.1 11.1 and 30.6 15.6 ug/mL*h. PK of T was similar with/without BZ (total AUC: 30.7 14.8 vs. 28.9 10.5). Inhibition of 20S proteasome with T+BZ was similar to BZ single-agent. PBLs maintained induction of Hsp70 throughout the 3-4 day dosing interval; D11 (pre-infusion at 340 mg/m2) showed similar Hsp70 induction for the Cremophor and suspension formulations. Myeloma CD138 cells but not CD4 or CD8 cells from serial BM aspirates showed induction of apoptosis by flow cytometry. Responses were seen across dose levels in BZ-na ve, pre-treated and refractory pts (defined as no response to or disease progression within 60d of last dose of BZ-containing regimen ). Three BZ-refractory pts achieved a durable response: 1 pt with 3 prior regimens with confirmed PR after 2 cycles, continuing 18+ months on study (M-spike 92%); a 2nd pt with 2 prior regimens achieved PR after 2 cycles and continues 14+ months on study; a 3rd pt with 7 prior regimens with confirmed PR withdrew after 8 cycles with 12-
Published in 2007.
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