title: Phase I trial of bortezomib during maintenance phase after high dose melphalan and autologous stem cell transplantation in patients with multiple myeloma.
abstract: We enrolled 15 patients in this phase I dose de-escalation trial. Twelve patients are evaluable. The primary objective was to determine the safest and best tolerated maintenance dosing (MD) of bortezomib (B). The secondary endpoints were to evaluate complete response (CR), overall response (OR) and response duration. All patients receiving autologous stem cell transplant (ASCT) were eligible and registered between D+30 to D+120 after ASCT. A maximum number of 8 cycles of B was planned. Two evaluable patients in level (L) 1 received therapeutic dose of B 1.3 mg/m(2) intravenously on days (D) 1, 4, 8, and 11 in a 21 day cycle. Both these patients experienced dose limiting toxicities (DLTs). Four evaluable patients were then enrolled in dose L2 utilizing B 1.3 mg/m(2) on D 1, 4, 8, and 11 in a 28 day cycle. Two patients in L2 developed DLTs. Six evaluable patients were thereafter enrolled in L3 utilizing B 1 mg/m(2) on D 1, 8, and 15 in a 28 day cycle. Median 8 cycles of B were administered (2-8). No DLTs were observed in L3. The median duration of follow up for the entire cohort is 33 months (12-62). The median duration of response in L3 is 29.1 months (12-33). We conclude that B 1 mg/m(2) administered intravenously and may be subcutaneously on D 1, 8, and 15 in a 28 day cycle is the best tolerated MD and can be safely given beginning around D+100 post-ASCT.
authors: Department of Bone Marrow Transplantation, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA. abidim@karmanos.org
authors: Muneer H
authors: MH
authors: Abidi
authors: Zartash
authors: Z
authors: Gul
authors: Judith
authors: J
authors: Abrams
authors: Lois
authors: L
authors: Ayash
authors: Abhinav
authors: A
authors: Deol
authors: Marie
authors: M
authors: Ventimiglia
authors: Lawrence
authors: L
authors: Lum
authors: Stephanie
authors: S
authors: Mellon-Reppen
authors: Zaid
authors: Z
authors: Al-Kadhimi
authors: Voravit
authors: V
authors: Ratanatharathorn
authors: Jeffrey
authors: J
authors: Zonder
authors: Joseph
authors: J
authors: Uberti
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000628:therapy; D011719:Pyrazines / Q000627:therapeutic use*; D012074:Remission Induction; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan