PMID- 21276608
OWN - NLM
STAT- MEDLINE
DCOM- 20110614
LR  - 20211020
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Print)
IS  - 0090-8258 (Linking)
VI  - 121
IP  - 2
DP  - 2011 May 1
TI  - A phase II, single-arm study of the anti-alpha5beta1 integrin antibody volociximab as 
      monotherapy in patients with platinum-resistant advanced epithelial ovarian or 
      primary peritoneal cancer.
PG  - 273-9
LID - 10.1016/j.ygyno.2010.12.362 [doi]
AB  - OBJECTIVE: This phase II, multicenter, single-arm, two-stage study in 
      platinum-resistant, advanced epithelial ovarian or primary peritoneal cancer 
      evaluated the efficacy, safety, and tolerability of weekly single-agent 
      volociximab. Pharmacokinetic/pharmacodynamic (PK/PD) studies were also performed. 
      METHODS: Sixteen patients were enrolled in Stage 1. Volociximab was administered 
      at 15mg/kg IV qwk until progression of disease or drug intolerability. Tumor 
      response was assessed every 8weeks. Serum samples for PK or whole blood for the 
      evaluation of circulating tumor cells, endothelial cells, and endothelial 
      progenitor cells were obtained on Days 1, 8, 15, 29, and 50. Ascites from one 
      patient was collected for volociximab concentration analysis. Archived tumor 
      tissue was analyzed by immunohistochemistry (IHC) for alpha5 integrin expression. 
      RESULTS: Safety data are available on all 16 patients; 14 were evaluable for 
      efficacy. One patient had stable disease at 8weeks. The remaining 13 progressed 
      on treatment. Twelve patients (75%) experienced study-related adverse events 
      (AEs); the most common (>/=20%) were headache and fatigue. Three patients 
      experienced possible study-related serious AEs (SAEs): reversible posterior 
      leukoencephalopathy syndrome, pulmonary embolism, and hyponatremia. Peak serum 
      concentrations of volociximab increased 2-3 fold from Day 1 to Day 50. Clinically 
      relevant trough levels were achieved (>150mug/mL). IHC analysis of archived tumor 
      sections showed low-to-moderate expression of alpha5 integrin on all ovarian cancer 
      tissue evaluated. CONCLUSION: Despite insufficient clinical activity in this 
      refractory patient population to continue the study, weekly volociximab was well 
      tolerated, and the gained understanding of the mechanism of action of volociximab 
      will inform future development efforts.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Bell-McGuinn, Katherine M
AU  - Bell-McGuinn KM
AD  - Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. 
      bell-mck@mskcc.org
FAU - Matthews, Carolyn M
AU  - Matthews CM
FAU - Ho, Steffan N
AU  - Ho SN
FAU - Barve, Minal
AU  - Barve M
FAU - Gilbert, Lucy
AU  - Gilbert L
FAU - Penson, Richard T
AU  - Penson RT
FAU - Lengyel, Ernst
AU  - Lengyel E
FAU - Palaparthy, Rameshraja
AU  - Palaparthy R
FAU - Gilder, Kye
AU  - Gilder K
FAU - Vassos, Artemios
AU  - Vassos A
FAU - McAuliffe, William
AU  - McAuliffe W
FAU - Weymer, Sara
AU  - Weymer S
FAU - Barton, Jeremy
AU  - Barton J
FAU - Schilder, Russell J
AU  - Schilder RJ
LA  - eng
GR  - R01 CA111882/CA/NCI NIH HHS/United States
GR  - U01 CA151461/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20110126
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Integrin alpha5beta1)
RN  - 0 (Organoplatinum Compounds)
RN  - 496K5Z02NW (volociximab)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/adverse effects/blood/immunology/*therapeutic use
MH  - Biomarkers, Tumor/blood
MH  - Carcinoma, Ovarian Epithelial
MH  - Drug Resistance, Neoplasm
MH  - Endothelial Cells/drug effects/pathology
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Integrin alpha5beta1/biosynthesis/immunology
MH  - Middle Aged
MH  - Neoplasms, Glandular and Epithelial/blood/drug therapy/immunology/pathology
MH  - Neoplastic Cells, Circulating/drug effects/pathology
MH  - Organoplatinum Compounds/pharmacology
MH  - Ovarian Neoplasms/blood/drug therapy/immunology/pathology
MH  - Peritoneal Neoplasms/blood/*drug therapy/immunology/pathology
MH  - Stem Cells/drug effects/pathology
PMC - PMC4426879
MID - NIHMS479533
COIS- Conflict of interest statement Katherine M. Bell-McGuinn: None. Carolyn M. 
      Matthews: None. Minal Barve: None. Lucy Gilbert: None. Russell J. Schilder: None.
EDAT- 2011/02/01 06:00
MHDA- 2011/06/15 06:00
PMCR- 2015/05/11
CRDT- 2011/02/01 06:00
PHST- 2010/11/11 00:00 [received]
PHST- 2010/12/27 00:00 [revised]
PHST- 2010/12/28 00:00 [accepted]
PHST- 2011/02/01 06:00 [entrez]
PHST- 2011/02/01 06:00 [pubmed]
PHST- 2011/06/15 06:00 [medline]
PHST- 2015/05/11 00:00 [pmc-release]
AID - S0090-8258(10)01269-2 [pii]
AID - 10.1016/j.ygyno.2010.12.362 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2011 May 1;121(2):273-9. doi: 10.1016/j.ygyno.2010.12.362. Epub 
      2011 Jan 26.