PMID- 20498386
OWN - NLM
STAT- MEDLINE
DCOM- 20100804
LR  - 20220318
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 28
IP  - 21
DP  - 2010 Jul 20
TI  - Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal 
      antibody, tremelimumab, in patients with refractory metastatic colorectal cancer.
PG  - 3485-90
LID - 10.1200/JCO.2010.28.3994 [doi]
AB  - PURPOSE: Safety and efficacy of tremelimumab (CP-675,206), a fully human 
      anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) monoclonal antibody, 
      were assessed in patients with treatment-refractory colorectal cancer. PATIENTS 
      AND METHODS: A single-arm, multicenter, phase II trial was conducted in patients 
      with Eastern Cooperative Oncology Group performance status <or= 1 and measurable 
      colorectal carcinoma for whom standard treatments for metastatic disease had 
      failed. Patients received 15 mg/kg tremelimumab intravenously every 90 days until 
      progression. Primary end point was objective response status (per Response 
      Evaluation Criteria in Solid Tumors). Secondary end points included safety, 
      duration of response, progression-free survival, and overall survival. RESULTS: 
      Forty-seven patients who had received extensive prior therapies (all had received 
      fluoropyrimidines, oxaliplatin, and irinotecan; most [91%] had also received 
      cetuximab) were treated. Grade 3/4 treatment-related adverse events (AEs) were 
      diarrhea (n = 5; 11%), ulcerative colitis (n = 1; 2%), fatigue (n = 1; 2%), 
      autoimmune thrombocytopenia (n = 1; 2%), and hypokalemia (n = 1; 2%), which 
      resolved spontaneously or with interventions. Six patients discontinued because 
      of an AE; two were considered treatment related. Of 45 response-evaluable 
      patients, 44 did not reach second dose (43 progressive disease; one 
      discontinuation). Twenty-one patients (45%) lived >or= 180 days after enrollment. 
      One patient (2%; 90% CI, < 1% to 10%) had a stable pelvic mass and substantial 
      regression in an adrenal mass (partial response). This patient received five 
      tremelimumab doses; response duration was 6 months (enrollment to disease 
      progression, 15 months). CONCLUSION: Tremelimumab did not demonstrate clinically 
      meaningful single-agent activity in this patient population, although the number 
      of survivors at 6 months and the one patient with confirmed partial response are 
      potentially interesting. Further study of tremelimumab in combination with other 
      agents may be warranted.
FAU - Chung, Ki Y
AU  - Chung KY
AD  - Gastrointestinal Medical Oncology Service, Memorial Sloan-Kettering Cancer 
      Center, New York, NY 10021, USA. chungk@mskcc.org
FAU - Gore, Ira
AU  - Gore I
FAU - Fong, Lawrence
AU  - Fong L
FAU - Venook, Alan
AU  - Venook A
FAU - Beck, Stephen B
AU  - Beck SB
FAU - Dorazio, Prudence
AU  - Dorazio P
FAU - Criscitiello, Peggy J
AU  - Criscitiello PJ
FAU - Healey, Diane I
AU  - Healey DI
FAU - Huang, Bo
AU  - Huang B
FAU - Gomez-Navarro, Jesus
AU  - Gomez-Navarro J
FAU - Saltz, Leonard B
AU  - Saltz LB
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20100524
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 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antigens, CD)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - QEN1X95CIX (tremelimumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/adverse effects/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized
MH  - Antigens, CD/immunology
MH  - CTLA-4 Antigen
MH  - Colorectal Neoplasms/*drug therapy/mortality
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
EDAT- 2010/05/26 06:00
MHDA- 2010/08/05 06:00
CRDT- 2010/05/26 06:00
PHST- 2010/05/26 06:00 [entrez]
PHST- 2010/05/26 06:00 [pubmed]
PHST- 2010/08/05 06:00 [medline]
AID - JCO.2010.28.3994 [pii]
AID - 10.1200/JCO.2010.28.3994 [doi]
PST - ppublish
SO  - J Clin Oncol. 2010 Jul 20;28(21):3485-90. doi: 10.1200/JCO.2010.28.3994. Epub 
      2010 May 24.