PMID- 23580070
OWN - NLM
STAT- MEDLINE
DCOM- 20131023
LR  - 20211021
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 139
IP  - 1
DP  - 2013 May
TI  - A multicenter trial evaluating retaspimycin HCL (IPI-504) plus trastuzumab in 
      patients with advanced or metastatic HER2-positive breast cancer.
PG  - 107-13
LID - 10.1007/s10549-013-2510-5 [doi]
AB  - Heat shock protein 90 (Hsp90) facilitates maturation and stability of HER2. 
      Combining an Hsp90 inhibitor and trastuzumab has demonstrated anti-tumor effects 
      in patients with HER2+ breast cancer. Adults with measurable, locally advanced or 
      metastatic HER2+ breast cancer and prior trastuzumab treatment were enrolled in a 
      phase 2 trial employing weekly 300 mg/m(2) retaspimycin HCl, a potent Hsp90 
      inhibitor, with 6 mg/kg trastuzumab every 3 weeks. A Simon's two-stage design 
      determined trial expansion by dose-limiting toxicity (DLT) and response rates. 
      Pharmacokinetics and electrocardiograms were evaluated. Twenty-six patients with 
      median age 52.5 years (range 33-72) enrolled with a median of six prior 
      chemotherapeutic regimens (range 2-20). On study, patients received a median of 
      three treatment cycles (range 1-12). No DLTs were observed. Most adverse events 
      (AEs) were grade 1 or 2; common treatment-related AEs included fatigue (46 %), 
      nausea (31 %), and diarrhea (23 %). One patient had treatment-related serious AEs 
      of grade 1 diarrhea and grade 3 hypokalemia. grade 3 transaminase elevation 
      occurred in one patient (4 %) who also had metastatic liver disease. Sixteen 
      patients (62 %) had stable disease, with a median on-study duration of 2.4 months 
      (range 1.1-8.2). No confirmed responses were observed. Retaspimycin HCl at 300 
      mg/m(2) weekly in combination with trastuzumab was well tolerated and without 
      significant toxicities. Modest clinical activity was observed, but did not meet 
      criteria for trial expansion. The safety profile for patients on study raises the 
      possibility of retaspimycin HCl underdosing that limited efficacy. Studies 
      employing higher doses are ongoing.
FAU - Modi, Shanu
AU  - Modi S
AD  - Memorial Sloan-Kettering Cancer Center/Weill Cornell Medical College, 300 East 
      66th Street, New York, NY 10065, USA. modis@mskcc.org
FAU - Saura, Cristina
AU  - Saura C
FAU - Henderson, Charles
AU  - Henderson C
FAU - Lin, Nancy U
AU  - Lin NU
FAU - Mahtani, Reshma
AU  - Mahtani R
FAU - Goddard, Jill
AU  - Goddard J
FAU - Rodenas, Eduardo
AU  - Rodenas E
FAU - Hudis, Clifford
AU  - Hudis C
FAU - O'Shaughnessy, Joyce
AU  - O'Shaughnessy J
FAU - Baselga, Jose
AU  - Baselga J
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20130412
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Benzoquinones)
RN  - 0 (Lactams, Macrocyclic)
RN  - 4GY0AVT3L4 (tanespimycin)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Benzoquinones/administration & dosage/adverse effects
MH  - Breast Neoplasms/*drug therapy/genetics/pathology
MH  - Disease-Free Survival
MH  - Female
MH  - Humans
MH  - Lactams, Macrocyclic/administration & dosage/adverse effects
MH  - Male
MH  - Middle Aged
MH  - Receptor, ErbB-2/biosynthesis/genetics
MH  - Trastuzumab
MH  - Treatment Outcome
PMC - PMC3646160
EDAT- 2013/04/13 06:00
MHDA- 2013/10/24 06:00
PMCR- 2013/04/12
CRDT- 2013/04/13 06:00
PHST- 2013/03/25 00:00 [received]
PHST- 2013/03/27 00:00 [accepted]
PHST- 2013/04/13 06:00 [entrez]
PHST- 2013/04/13 06:00 [pubmed]
PHST- 2013/10/24 06:00 [medline]
PHST- 2013/04/12 00:00 [pmc-release]
AID - 2510 [pii]
AID - 10.1007/s10549-013-2510-5 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2013 May;139(1):107-13. doi: 10.1007/s10549-013-2510-5. 
      Epub 2013 Apr 12.