Combination therapy for advanced pancreatic cancer using Herceptin plus chemotherapy.
The HER2/neu oncogene is overexpressed in up to 70% of human pancreatic cancer specimens when compared to normal pancreatic tissue. This cell surface receptor can be targeted specifically by the neutralizing antibody Herceptin. Herceptin has been successfully used in combination with other chemotherapeutic agents in breast cancer, a cancer in which only 30% of patients harbor elevated HER2/neu levels. In the present study, we investigated the therapeutic efficacy of Herceptin in combination with gemcitabine and docetaxel. Gemcitabine is currently the standard chemotherapeutic agent used to treat pancreatic cancer. In contrast, docetaxel, a taxane, is only just being investigated in pancreatic cancer. Tumor cell resistance to taxanes is at least in part mediated by the HER2/NEU oncogene. We have previously characterized HER2/NEU expression in human pancreatic cancer cell lines and studied the anti-tumor activity of Herceptin monotherapy in vitro and in vivo. In the present study, combination therapy resulted in a dramatic improvement of animals bearing human pancreatic cancer xenografts. Furthermore, metastasis and production of ascites was lower when a combination of these three agents was used. We conclude that, as with breast cancer, the anti-tumor activity of Herceptin may be improved by combination with taxanes or gemcitabine.
Büchler
Peter
P
Department of General Surgery, Ruprecht-Karls-University of Heidelberg, D-69120 Heidelberg, Germany. peter.buechler@med.uni-heidelberg.de
Reber
Howard A
HA
Eibl
Guido
G
Roth
Mendel A
MA
Büchler
Markus W
MW
Friess
Helmut
H
Isacoff
William H
WH
Hines
Oscar J
OJ
D000362:Agar / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001201:Ascites / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000737:chemistry; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry; D013997:Time Factors; D000068878:Trastuzumab; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000362:Agar; D000068878:Trastuzumab; D000093542:Gemcitabine