PMID- 16135466
OWN - NLM
STAT- MEDLINE
DCOM- 20050920
LR  - 20201222
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 23
IP  - 25
DP  - 2005 Sep 1
TI  - Study of etanercept, a tumor necrosis factor-alpha inhibitor, in recurrent 
      ovarian cancer.
PG  - 5950-9
AB  - PURPOSE: Convincing data support the link between inflammation and ovarian 
      cancer. Tumor necrosis factor-alpha (TNF-alpha), a major mediator of 
      inflammation, is chronically produced in the ovarian tumor microenvironment and 
      may enhance tumor growth and invasion by inducing the secretion of cytokines, 
      proangiogenic factors, and metalloproteinases. Etanercept is a recombinant human 
      soluble p75 TNF receptor that binds to TNF-alpha and renders it biologically 
      unavailable. In the current study, we sought to determine the toxicity, biologic 
      activity, and therapeutic efficacy of etanercept in recurrent ovarian cancer. 
      PATIENTS AND METHODS: We initiated a phase I-B, nonrandomized, open-label study 
      in patients with recurrent ovarian cancer. Etanercept was administered 
      subcutaneously at a dose of 25 mg twice weekly (cohort one) and 25 mg thrice 
      weekly (cohort two) until disease progression. RESULTS: Thirty patients were 
      recruited (cohort one, 17 patients; cohort two, 13 patients). Eighteen of the 30 
      patients (cohort one, 11 patients; cohort two, seven patients) completed > or = 
      12 weeks of treatment. Six patients achieved prolonged disease stabilization 
      (cohort one, two patients [40 and 25 weeks]; cohort two, four patients [34, 24, 
      22, and 24 weeks]). A significant rise in immunoreactive TNF was seen in all 
      patients (pretreatment compared with end of treatment). A 
      phytohemagglutinin-stimulated whole-blood cytokine assay showed a significant 
      fall in interleukin-6 (cohort one [11 of 17]) and CCL2 (cohort one [13 of 17]) 
      levels. Common adverse effects were injection-site reactions and fatigue. 
      CONCLUSION: We provide evidence for the biologic activity and safety of 
      etanercept in recurrent ovarian cancer. Our data suggest possible clinical 
      activity that must be confirmed in future studies.
FAU - Madhusudan, Srinivasan
AU  - Madhusudan S
AD  - Cancer Research UK Medical Oncology Unit, University of Oxford, Churchill 
      Hospital, Oxford, United Kingdom.
FAU - Muthuramalingam, Sethupathi R
AU  - Muthuramalingam SR
FAU - Braybrooke, Jeremy P
AU  - Braybrooke JP
FAU - Wilner, Susan
AU  - Wilner S
FAU - Kaur, Kulwinder
AU  - Kaur K
FAU - Han, Cheng
AU  - Han C
FAU - Hoare, Susan
AU  - Hoare S
FAU - Balkwill, Frances
AU  - Balkwill F
FAU - Ganesan, Trivadi S
AU  - Ganesan TS
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunologic Factors)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Etanercept
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/administration & dosage/adverse effects/*therapeutic use
MH  - Immunologic Factors/administration & dosage/adverse effects/*therapeutic use
MH  - Injections, Subcutaneous
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/*pathology
MH  - Ovarian Neoplasms/*drug therapy/*pathology
MH  - Receptors, Tumor Necrosis Factor/administration & dosage/*therapeutic use
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors
EDAT- 2005/09/02 09:00
MHDA- 2005/09/21 09:00
CRDT- 2005/09/02 09:00
PHST- 2005/09/02 09:00 [pubmed]
PHST- 2005/09/21 09:00 [medline]
PHST- 2005/09/02 09:00 [entrez]
AID - 23/25/5950 [pii]
AID - 10.1200/JCO.2005.04.127 [doi]
PST - ppublish
SO  - J Clin Oncol. 2005 Sep 1;23(25):5950-9. doi: 10.1200/JCO.2005.04.127.