New developments in chemotherapy of advanced breast cancer

• Published in: Annals of oncology Vol. 10; no. suppl-6; pp. S139 - S146
• Main Authors: Lebwohl, D.E., Canetta, R.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 1999; Oxford University Press
• Subjects: anthracycline; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzhydryl Compounds - administration & dosage; Benzhydryl Compounds - therapeutic use; Biological and medical sciences; BMS-217380-01; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Chemotherapy; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; HER-2 antibody; Humans; Medical sciences; N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01); N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE; paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - therapeutic use; Pharmacology. Drug treatments; Phenyl Ethers; Randomized Controlled Trials as Topic; Trastuzumab; paclitaxel; breast cancer; HER-2 antibody; anthracycline; chemotherapy; N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01); Antineoplastic agent; Drug combination; Monoclonal antibody; Malignant tumor; Doxorubicin; Mammary gland diseases; Chemotherapy; Treatment; Immunotherapy; Taxane derivatives; Paclitaxel; Advanced stage; Anthracyclins; Mammary gland; Onc gene; Trastuzumab
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/10.suppl_6.S139

Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/pachtaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimised; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in >25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomised trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents are discussed. As new anthracycline/taxane combinations establish themselves in earlier stages of the disease, the need for effective, non-cross resistant salvage regimens will emerge.