PMID- 18463870
OWN - NLM
STAT- MEDLINE
DCOM- 20081030
LR  - 20151119
IS  - 1432-0584 (Electronic)
IS  - 0939-5555 (Linking)
VI  - 87
IP  - 8
DP  - 2008 Aug
TI  - Safety and efficacy of bortezomib and melphalan combination in patients with 
      relapsed or refractory multiple myeloma: updated results of a phase 1/2 study 
      after longer follow-up.
PG  - 623-31
LID - 10.1007/s00277-008-0501-0 [doi]
AB  - Bortezomib synergizes with melphalan in preclinical and early clinical studies. 
      Updated data from our phase 1/2 study assessing the safety and efficacy of 
      bortezomib plus melphalan in relapsed/refractory multiple myeloma (MM) are 
      presented. Bortezomib (0.7, 1.0, or 1.3 mg/m(2)) on days 1, 4, 8, and 11 and oral 
      melphalan (0.025-0.25 mg/kg) on days 1-4 of a 28-day cycle were administered. 
      Hematologic toxicities defined the maximum tolerated dose as bortezomib 1.0 
      mg/m(2) and melphalan 0.10 mg/kg. Because dose-limiting toxicities were 
      attributed to the more myelosuppressive melphalan, cohorts 9 and 10 with higher 
      bortezomib (1.3 mg/m(2)) and lower melphalan (0.025 and 0.10 mg/kg) doses were 
      added. Responses occurred in 32/46 (70%) evaluable patients: two complete (4%), 
      five near-complete (11%), 16 partial (35%), and nine minimal (20%). Complete and 
      near-complete responses were observed only with higher bortezomib doses. Response 
      rates were similar in patients with prior melphalan or bortezomib. Median 
      progression-free survival was 9 months (range, 1-24), and overall survival was 32 
      months (range, 1-54). The most common grade 3/4 hematologic adverse events (AEs) 
      were neutropenia (31%/0%), thrombocytopenia (25%/2%), and anemia (13%/0%). Grade 
      4 tumor lysis syndrome was reported in one patient. Fewer grade 3/4 hematologic 
      AEs were reported in cohorts 9 and 10 than in cohorts receiving lower bortezomib 
      and higher melphalan doses. In conclusion, bortezomib plus melphalan is a 
      steroid- and immunomodulatory drug-free regimen that may provide a treatment 
      alternative for elderly patients and patients with significant comorbidity.
FAU - Berenson, James R
AU  - Berenson JR
AD  - Institute for Myeloma and Bone Cancer Research, West Hollywood, CA 90069, USA. 
      jberenson@imbcr.org
FAU - Yang, Hank H
AU  - Yang HH
FAU - Vescio, Robert A
AU  - Vescio RA
FAU - Nassir, Youram
AU  - Nassir Y
FAU - Mapes, Russell
AU  - Mapes R
FAU - Lee, Shi-Pyng
AU  - Lee SP
FAU - Wilson, Joanna
AU  - Wilson J
FAU - Yellin, Ori
AU  - Yellin O
FAU - Morrison, Blake
AU  - Morrison B
FAU - Hilger, Jacqueline
AU  - Hilger J
FAU - Swift, Regina
AU  - Swift R
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20080508
PL  - Germany
TA  - Ann Hematol
JT  - Annals of hematology
JID - 9107334
RN  - 0 (Boronic Acids)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - Q41OR9510P (Melphalan)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anemia/chemically induced
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects
MH  - Boronic Acids/administration & dosage/adverse effects
MH  - Bortezomib
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Melphalan/administration & dosage/adverse effects
MH  - Middle Aged
MH  - Multiple Myeloma/*drug therapy
MH  - Neoplasm Recurrence, Local/*drug therapy
MH  - Neutropenia/chemically induced
MH  - Pyrazines/administration & dosage/adverse effects
MH  - Thrombocytopenia/chemically induced
EDAT- 2008/05/09 09:00
MHDA- 2008/10/31 09:00
CRDT- 2008/05/09 09:00
PHST- 2008/02/19 00:00 [received]
PHST- 2008/04/15 00:00 [accepted]
PHST- 2008/05/09 09:00 [pubmed]
PHST- 2008/10/31 09:00 [medline]
PHST- 2008/05/09 09:00 [entrez]
AID - 10.1007/s00277-008-0501-0 [doi]
PST - ppublish
SO  - Ann Hematol. 2008 Aug;87(8):623-31. doi: 10.1007/s00277-008-0501-0. Epub 2008 May 
      8.