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HER‐2 profiling and targeting in prostate carcinoma
Author(s) -
Morris Michael J.,
Reuter Victor E.,
Kelly W. Kevin,
Slovin Susan F.,
Kenneson Kate,
Verbel David,
Osman Iman,
Scher Howard I.
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10339
Subject(s) - medicine , trastuzumab , prostate , oncology , prostate cancer , paclitaxel , carcinoma , prostate carcinoma , confidence interval , prostate specific antigen , gastroenterology , chemotherapy , cancer , breast cancer
Abstract 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 ≥ 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. Cancer 2002;94:980–6. © 2002 American Cancer Society. DOI 10.1002/cncr.10339