Pharmacologic insights into the future of trastuzumab

A combination of factors has been responsible for improvements in cancer su rvival and cure rates. In addition to new therapies with novel/genetic targ ets, these include improvements in drug delivery, new schedules/sequencing of drug administration and the identification of combination therapies with greater activity/dose density than existing regimens. The recognition that such criteria can affect treatment outcome has led to their incorporation into clinical trials of new drugs. Furthermore, pharmacokinetic and pharmac odynamic parameters have become increasingly important for the rational sel ection of dose, administration route and schedule. The humanized monoclonal antibody trastuzumab (Herceptin) has been rationally developed to target t he human epidermal growth factor receptor-2 (HER2), which is overexpressed in 20%-30% of breast cancers and is associated with poor prognosis. Trastuz umab when administered i.v. on a weekly schedule either alone or in combina tion with taxanes, improves survival of women with HER2-positive metastatic breast cancer. Based upon pharmacokinetic considerations, current studies are examining whether trastuzumab can be administered i.v. every three week s or by the s.c. route. These regimens would have advantages for patients a nd medical staff in terms of acceptability, ease of administration and, pot entially, cost effectiveness. Furthermore, various combinations of trastuzu mab and chemotherapeutic agents are being explored with the aim of identify ing the optimal combination regimen for clinical use. The rationale for the se various studies and the studies themselves are described.