Enhanced Antitumor Activity of Paclitaxel in Combination with the Anticarcinoma Immunoconjugate BR96-Doxorubicin

• Published in: Clinical cancer research 1999-11, Vol.5 (11), p.3632-3638
• Main Authors: TRAIL, P. A, WILLNER, D, BIANCHI, A. B, HENDERSON, A. J, TRAILSMITH, M. D, GIRIT, E, LASCH, S, HELLSTRÖM, I, HELLSTRÖM, K. E
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - pathology; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Chemotherapy; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Medical sciences; Mice; Mice, Nude; Neoplasms - drug therapy; Neoplasms - pathology; Paclitaxel - administration & dosage; Paclitaxel - therapeutic use; Pharmacology. Drug treatments; Rats; Rats, Nude; Time Factors; Transplantation, Heterologous; Tumor Cells, Cultured
• ISSN: 1078-0432; 1557-3265

The efficacy of chemotherapy has been improved by regimens that combine several cytotoxic drugs with different mechanisms of action and/or different dose-limiting toxicities. Here we demonstrate clearly, and for the first time, that combined therapy using an anticarcinoma immunoconjugate, BR96-doxorubicin, and the cytotoxic drug paclitaxel results in a significant increase in antitumor activity over that of either agent alone. Synergistic activity was seen at doses of BR96-doxorubicin that were minimally active as single agents. A dramatic increase in regression rates was seen when a regimen that combined BR96-doxorubicin and paclitaxel was used to treat both paclitaxel-sensitive and paclitaxel-insensitive carcinomas. Importantly, combined therapy resulted in increased antitumor activity against lung, colon, and breast tumors xenografted in athymic mice and large, paclitaxel-insensitive colon tumors xenografted in athymic rats that also express the Lewis y target antigen in normal tissues.