PMID- 22281842
OWN - NLM
STAT- MEDLINE
DCOM- 20121024
LR  - 20120821
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 118
IP  - 17
DP  - 2012 Sep 1
TI  - An open-label, phase 2 trial of RPI.4610 (Angiozyme) in the treatment of 
      metastatic breast cancer.
PG  - 4098-104
LID - 10.1002/cncr.26730 [doi]
AB  - BACKGROUND: Serum and plasma levels of vascular endothelial growth factor (VEGF) 
      correlate with prognosis in patients with metastatic breast cancer (MBC). VEGF 
      binds to 2 receptors on endothelial cells, VEGFR-1 and VEGFR-2. RPI.4610 
      (Angiozyme0) is an antiangiogenic ribozyme targeting the VEGFR-1 mRNA. 
      Preclinical and phase 1 studies suggested that RPI.4610 is a well-tolerated agent 
      with clinical activity in solid tumors. The authors' trial evaluated the efficacy 
      of RPI.4610 in the treatment of patients with progressive MBC. METHODS: This 
      phase 2, multicenter, single-arm study was designed to assess the objective 
      response rate of RPI.4610 in patients with MBC who had experienced disease 
      progression with at least 1 course of chemotherapy for MBC. Patients received 
      daily subcutaneous injections of RPI.4610 100 mg/m(2) for 12 weeks. RESULTS: Most 
      patients (93%) had received at least 2 lines of chemotherapy previously; 69% of 
      patients had received at least 3 lines of chemotherapy. Median follow-up was 2.76 
      months (range, 0.89-36.6 months). No partial responses nor complete responses 
      were found. Median progression-free survival was 1.41 months (95% confidence 
      interval [CI], 1.35-1.45). The median overall survival from start of treatment 
      was 11.89 months (95% CI, 4.11-23.66). Treatment-related adverse events (AEs) 
      were primarily grade 1 to 2 in intensity. Most common AEs were: injection site 
      reactions, abdominal pain, anorexia, chromaturia, constipation, dyspnea, fatigue, 
      headache, pain at the injection site, nausea, vomiting, and fever. CONCLUSIONS: 
      Although RPI.4610 demonstrated a well-tolerated safety profile, its lack of 
      clinical efficacy precludes this drug from further development.
CI  - Copyright (c) 2012 American Cancer Society.
FAU - Morrow, Phuong Khanh
AU  - Morrow PK
AD  - The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 
      pmorrow@mdanderson.org
FAU - Murthy, Rashmi K
AU  - Murthy RK
FAU - Ensor, Joe D
AU  - Ensor JD
FAU - Gordon, Gilad S
AU  - Gordon GS
FAU - Margolin, Kim A
AU  - Margolin KA
FAU - Elias, Anthony D
AU  - Elias AD
FAU - Urba, Walter J
AU  - Urba WJ
FAU - Weng, David E
AU  - Weng DE
FAU - Rugo, Hope S
AU  - Rugo HS
FAU - Hortobagyi, Gabriel N
AU  - Hortobagyi GN
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120126
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Angiozyme)
RN  - 0 (RNA, Catalytic)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/pathology/secondary
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - RNA, Catalytic/adverse effects/*therapeutic use
MH  - Vascular Endothelial Growth Factor Receptor-1/antagonists & inhibitors
EDAT- 2012/01/28 06:00
MHDA- 2012/10/25 06:00
CRDT- 2012/01/28 06:00
PHST- 2011/06/27 00:00 [received]
PHST- 2011/09/26 00:00 [revised]
PHST- 2011/10/13 00:00 [accepted]
PHST- 2012/01/28 06:00 [entrez]
PHST- 2012/01/28 06:00 [pubmed]
PHST- 2012/10/25 06:00 [medline]
AID - 10.1002/cncr.26730 [doi]
PST - ppublish
SO  - Cancer. 2012 Sep 1;118(17):4098-104. doi: 10.1002/cncr.26730. Epub 2012 Jan 26.