PMID- 16832816
OWN - NLM
STAT- MEDLINE
DCOM- 20061002
LR  - 20151119
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 107
IP  - 5
DP  - 2006 Sep 1
TI  - Phase II study of single-agent bortezomib for the treatment of patients with 
      fludarabine-refractory B-cell chronic lymphocytic leukemia.
PG  - 916-24
AB  - Therapeutic options are limited and the prognosis is poor for patients with 
      fludarabine-refractory B-cell chronic lymphocytic leukemia (CLL). Bortezomib 
      induces apoptosis in vitro in CLL cells, both alone and in combination, including 
      in cells resistant to fludarabine or other agents. The aim of the current 
      randomized, open-label, Phase II study was to investigate the clinical activity 
      of bortezomib in patients with fludarabine-refractory B-cell CLL. Twenty-two 
      patients with histologically confirmed B-cell CLL were treated with bortezomib at 
      doses of 1.0 mg/m2, 1.3 mg/m2, or 1.5 mg/m2 on Days 1, 4, 8, and 11 of a 21-day 
      treatment cycle for a maximum of 9 cycles. None of 19 patients evaluable for 
      response achieved complete remission or partial response; however, signs of 
      biologic activity based on disease site responses (e.g., reduction in 
      lymphocytosis, splenomegaly, and lymphadenopathy) were observed. In the 1.5 mg/m2 
      dose group, a higher proportion of patients had stable disease, and a lower 
      proportion had progressive disease compared with the 2 lower-dose groups. Eleven 
      patients, all in the 2 higher dose groups, experienced Grade 3/4 adverse events 
      (AEs) (according to National Cancer Institute Common Toxicity Criteria [version 
      2.0]); 2 patients experienced Grade 4 neutropenia. Grade 3 hematologic AEs 
      included anemia, neutropenia, thrombocytopenia, and hemolytic anemia; Grade 3 
      nervous system AEs included aphasia; peripheral neuropathy, not otherwise 
      specified; and peripheral sensory neuropathy. Although no objective responses 
      were achieved in patients with fludarabine-refractory B-cell CLL, single-agent 
      bortezomib demonstrated biologic activity. In view of the evidence for its 
      activity, further exploration of bortezomib in combination with other agents is 
      warranted.
FAU - Faderl, Stefan
AU  - Faderl S
AD  - Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, 
      Houston, Texas 77030, USA.
FAU - Rai, Kanti
AU  - Rai K
FAU - Gribben, John
AU  - Gribben J
FAU - Byrd, John C
AU  - Byrd JC
FAU - Flinn, Ian W
AU  - Flinn IW
FAU - O'Brien, Susan
AU  - O'Brien S
FAU - Sheng, Shihong
AU  - Sheng S
FAU - Esseltine, Dixie-Lee
AU  - Esseltine DL
FAU - Keating, Michael J
AU  - Keating MJ
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Boronic Acids)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Pyrazines)
RN  - 69G8BD63PP (Bortezomib)
RN  - FA2DM6879K (Vidarabine)
RN  - P2K93U8740 (fludarabine)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Boronic Acids/administration & dosage/*therapeutic use
MH  - Bortezomib
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Protease Inhibitors/*therapeutic use
MH  - Pyrazines/administration & dosage/*therapeutic use
MH  - Treatment Outcome
MH  - Vidarabine/analogs & derivatives/pharmacology
EDAT- 2006/07/13 09:00
MHDA- 2006/10/03 09:00
CRDT- 2006/07/13 09:00
PHST- 2006/07/13 09:00 [pubmed]
PHST- 2006/10/03 09:00 [medline]
PHST- 2006/07/13 09:00 [entrez]
AID - 10.1002/cncr.22097 [doi]
PST - ppublish
SO  - Cancer. 2006 Sep 1;107(5):916-24. doi: 10.1002/cncr.22097.