[Feasibility of targeted therapy based on immunohistochemical expression analysis in androgen-independent prostate cancer].
Targeted therapies present an interesting treatment option in prostate cancer. The aim of our study was to analyze the expression profile of several molecular markers that are candidates for targeted therapy in patients with progressive androgen-independent prostate cancer (AIPC). Based on the expression profile, the efficacy of a combination therapy with a signal transduction inhibitor (STI) and docetaxel was evaluated.Tumor tissue obtained from biopsy of the prostate or lymph node and visceral metastasis was analyzed for the immunohistochemical expression of epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor beta (PDGFRbeta), Her-2/neu, c-KIT, and vascular endothelial growth factor (VEGF). Patients with positive staining of one or more markers were treated with the corresponding STI and docetaxel.Fifty-one patients were included in the protocol, of whom 43 (84.3%) presented with progressive AIPC after first-line chemotherapy. Forty-six of these 51 patients (90.2%) showed expression of one or more of the analyzed markers. Expression of EGFR was found in 61.2%, PDGFRbeta in 57.1%, Her-2/neu in 16.3%, c-KIT in 25.0%, and VEGF in 74.5%. After request for cost coverage, 8/51 patients received the combination therapy and were evaluated for response. Four of the eight patients (50%) showed a decline in prostate-specific antigen of > or =50%, and median survival time was 13.5 months at a median follow-up of 23.6 (11-35) months.The results show that expression of molecular targets is found in about 90% of patients with AIPC. Based on the expression profile, an individual treatment strategy can be applied to each patient. Further clinical studies should determine the clinical efficacy of molecular targeted therapy in patients with AIPC.
Ohlmann
C-H
CH
Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland. Carsten.Ohlmann@uks.eu
Markert
E
E
Gerharz
M
M
Pfister
D
D
Dienes
H-P
HP
Engelmann
U
U
Heidenreich
A
A
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D000068818:Cetuximab; D018450:Disease Progression; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006801:Humans; D000068877:Imatinib Mesylate; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001549:Benzamides; D014408:Biomarkers, Tumor; D010879:Piperazines; D011743:Pyrimidines; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel; D000068258:Bevacizumab; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D017430:Prostate-Specific Antigen; D000068878:Trastuzumab; D000068818:Cetuximab