PMID- 11920466
OWN - NLM
STAT- MEDLINE
DCOM- 20020415
LR  - 20151119
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 94
IP  - 4
DP  - 2002 Feb 15
TI  - HER-2 profiling and targeting in prostate carcinoma.
PG  - 980-6
AB  - BACKGROUND: The clinical effects of targeting HER-2 in prostate carcinoma are not 
      known. This study explored the feasibility of molecular profiling to determine 
      the correlation between HER-2 expression, hormonal sensitivity, and the antitumor 
      effects of trastuzumab and paclitaxel in patients with prostate carcinoma. 
      METHODS: Patients with progressive androgen dependent (AD) and androgen 
      independent (AI) prostate carcinoma were eligible to participate in the study. 
      HER-2 expression was assessed on pretreatment tissue specimens, and patients were 
      then assigned to one of four treatment groups: AD HER-2 positive, AD HER-2 
      negative, AI HER-2 positive, and AI HER-2 negative. They were treated with weekly 
      trastuzumab at a dose of 2 mg/kg (after a 4 mg/kg loading dose) until they 
      experienced disease progression, when weekly paclitaxel at 100 mg/m(2) was added. 
      RESULTS: The authors screened 130 patients for HER-2 expression. In total, 23 
      patients were treated. Six eligible patients had HER-2 positive disease; 
      therefore, only the AI HER-2 negative arm accrued to completion. All patients 
      (100%) experienced disease progression on trastuzumab alone at or before the 
      first 12 weeks of treatment. Fifteen patients received combined therapy: Seven 
      patients (47%) experienced disease progression, 5 patients (33%) had stable 
      disease, and 3 patients (20%) had a decline > or = 50% in prostate specific 
      antigen PSA level or in soft tissue disease. HER-2 overexpression was found in 
      significant proportions only in AI metastatic tissue samples (42% HER-2 positive; 
      95% confidence interval, 14-60%). In three of nine matched pairs, the AD prostate 
      biopsy was HER-2 negative, and the AI metastatic sample was HER-2 positive. 
      CONCLUSIONS: Trastuzumab is not effective as a single agent for the treatment of 
      patients with AI HER-2 negative tumors. HER-2 expression varies by clinical state 
      in patients with prostate carcinoma: Accurate HER-2 profiling requires sampling 
      metastatic tissue in patients with metastatic disease. Further development of 
      trastuzumab for the treatment of patients with metastatic prostate carcinoma is 
      not feasible until more reliable and practical methods of sampling metastatic 
      disease are developed to identify patients with HER-2 positive tumors.
CI  - Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10339
FAU - Morris, Michael J
AU  - Morris MJ
AD  - Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
FAU - Reuter, Victor E
AU  - Reuter VE
FAU - Kelly, W Kevin
AU  - Kelly WK
FAU - Slovin, Susan F
AU  - Slovin SF
FAU - Kenneson, Kate
AU  - Kenneson K
FAU - Verbel, David
AU  - Verbel D
FAU - Osman, Iman
AU  - Osman I
FAU - Scher, Howard I
AU  - Scher HI
LA  - eng
GR  - CA 09207/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - P188ANX8CK (Trastuzumab)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/administration & dosage/*pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Agents/administration & dosage/*pharmacology
MH  - Antineoplastic Agents, Phytogenic/administration & dosage/*pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Carcinoma/*drug therapy/*genetics/pathology
MH  - Disease Progression
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Paclitaxel/administration & dosage/*pharmacology
MH  - Prostate-Specific Antigen/blood
MH  - Prostatic Neoplasms/*drug therapy/*genetics/pathology
MH  - Receptor, ErbB-2/*biosynthesis
MH  - Trastuzumab
MH  - Treatment Outcome
EDAT- 2002/03/29 10:00
MHDA- 2002/04/16 10:01
CRDT- 2002/03/29 10:00
PHST- 2002/03/29 10:00 [pubmed]
PHST- 2002/04/16 10:01 [medline]
PHST- 2002/03/29 10:00 [entrez]
AID - 10.1002/cncr.10339 [pii]
PST - ppublish
SO  - Cancer. 2002 Feb 15;94(4):980-6.