Interactions of antioestrogens and aromatase inhibitors.
Aromatase inhibitors and antioestrogens have shown substantial activity in primary and advanced breast cancer. Since they exhibit different modes of action, attempts have been made to combine them or to use them sequentially in order to potentially increase their efficacy. In preclinical studies, combined, sequential or alternating treatments with aromatase inhibitors and antioestrogens have failed to provide higher antitumoural activity. There are relevant pharmacokinetic interactions resulting in decreased plasma concentrations of third generation aromatase inhibitors when combined with tamoxifen. Several randomised clinical trials comparing single agent and combined treatment with tamoxifen and aminoglutethimide failed to show any benefit for the combination. Early results of the adjuvant ATAC trial indicate that single agent anastrozole is superior to tamoxifen or the combination of both. Several trials are ongoing which might help to further define the role of sequential or combined treatment with aromatase inhibitors and antioestrogens. However, to date, looking at the current evidence, combined treatment with aromatase inhibitors and antioestrogens does not appear to provide additional benefit compared to single agent treatment.
Schmid
Peter
P
Department of Oncology and Hematology, Charité Campus Mitte, Humboldt University Berlin, Germany.
Possinger
Kurt
K
D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists