PMID- 23589214
OWN - NLM
STAT- MEDLINE
DCOM- 20141007
LR  - 20211021
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Linking)
VI  - 32
IP  - 1
DP  - 2014 Feb
TI  - Safety, pharmacokinetics, and pharmacodynamics of the DR5 antibody LBY135 alone 
      and in combination with capecitabine in patients with advanced solid tumors.
PG  - 135-44
LID - 10.1007/s10637-013-9952-9 [doi]
AB  - PURPOSE: We evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics, 
      pharmacodynamics, biologic activity, and antitumor efficacy of the DR5 antibody, 
      LBY135 +/- capecitabine. EXPERIMENTAL DESIGN: Escalating LBY135 was administered 
      every 21 days, alone (Arm1) or with capecitabine (Arm2), to patients with 
      advanced solid tumors. RESULTS: In Arm1 (n = 40), LBY135 (0.3-40 mg/kg) resulted 
      in no dose-limiting toxicities (DLTs); adverse events (AEs) included fatigue, 
      hypotension, abdominal pain, dyspnea, and nausea. Stable disease (SD) was 
      observed in 21/38 (55.3 %) patients. In Arm2 (n = 33), LBY135 (1-40 mg/kg) plus 
      capecitabine resulted in 3 DLTs (each grade 3): dehydration and mucosal 
      inflammation (1 mg/kg), colitis (20 mg/kg), and diarrhea (40 mg/kg). AEs included 
      fatigue, nausea, dyspnea, and vomiting. Partial response was observed in 2 
      patients (rectal and breast cancer) and SD in 12/27 (44.4 %) patients. Mean 
      elimination half-life of LBY135 +/- capecitabine at saturation of clearance (>/=10 
      mg/kg) ranged between 146 h and 492 h. Immunogenicity was detected in 16/73 (22 
      %) patients, of which 6 patients experienced reduced LBY135 exposure with repeat 
      dosing. M30/M65 levels were not predictive for LBY135 response. FDG-PET responses 
      were not consistently associated with RECIST responses. CONCLUSIONS: LBY135 was 
      well tolerated up to 40 mg/kg, the maximal dose administered; no MTD for LBY135 +/- 
      capecitabine was defined. Clearance was saturated at doses >/=10 mg/kg.
FAU - Sharma, Sunil
AU  - Sharma S
AD  - Huntsman Cancer Institute, Division of Medical Oncology, University of Utah, 2000 
      Circle of Hope Drive, Suite 3380, Salt Lake City, UT, 84112, USA, 
      Sunil.Sharma@hci.utah.edu.
FAU - de Vries, Elisabeth G
AU  - de Vries EG
FAU - Infante, Jeffrey R
AU  - Infante JR
FAU - Oldenhuis, Corina N
AU  - Oldenhuis CN
FAU - Gietema, Jourik A
AU  - Gietema JA
FAU - Yang, Lin
AU  - Yang L
FAU - Bilic, Sanela
AU  - Bilic S
FAU - Parker, Katie
AU  - Parker K
FAU - Goldbrunner, Michael
AU  - Goldbrunner M
FAU - Scott, Jeffrey W
AU  - Scott JW
FAU - Burris, Howard A 3rd
AU  - Burris HA 3rd
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130416
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antibodies)
RN  - 0 (Antibodies, Monoclonal, Murine-Derived)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (LBY135 monoclonal antibody)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies/*adverse effects/pharmacology/*therapeutic use
MH  - Antibodies, Monoclonal, Murine-Derived/*adverse effects/pharmacology/*therapeutic 
      use
MH  - Antineoplastic Agents/adverse effects/pharmacokinetics/pharmacology/therapeutic 
      use
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/*pharmacokinetics/pharmacology/*therapeutic use
MH  - Capecitabine
MH  - Demography
MH  - Deoxycytidine/analogs & derivatives/therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fluorodeoxyglucose F18
MH  - Fluorouracil/analogs & derivatives/therapeutic use
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Neoplasms/blood/diagnostic imaging/*drug therapy/pathology
MH  - Positron-Emission Tomography
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*immunology
EDAT- 2013/04/17 06:00
MHDA- 2014/10/08 06:00
CRDT- 2013/04/17 06:00
PHST- 2013/01/29 00:00 [received]
PHST- 2013/03/15 00:00 [accepted]
PHST- 2013/04/17 06:00 [entrez]
PHST- 2013/04/17 06:00 [pubmed]
PHST- 2014/10/08 06:00 [medline]
AID - 10.1007/s10637-013-9952-9 [doi]
PST - ppublish
SO  - Invest New Drugs. 2014 Feb;32(1):135-44. doi: 10.1007/s10637-013-9952-9. Epub 
      2013 Apr 16.