The European experience with docetaxel in the treatment of early-stage breast cancer.
This article summarizes the European experience with docetaxel in the adjuvant treatment of breast cancer patients. Four categories of trials evaluating the role of docetaxel are discussed: (1) 2-arm trial in which an anthracycline-based regimen administered for 6-8 cycles is compared to 3-4 cycles of the same regimen followed by full doses of 3-4 cycles of docetaxel; (2) 2-arm trial in which anthracycline-based polychemotherapy is compared to an anthracycline/docetaxel-based regimen; (3) 4-arm trial in which 2 different concepts are under evaluation: the role of docetaxel and the comparison between different anthracycline/docetaxel-based regimens, in which the 2 drugs are administered either in combination or sequentially; (4) translational research prospective trials aiming to identify a specific subgroup of patients deriving the largest benefit from the use of docetaxel. While it is expected that these trials will show the superiority of the docetaxel-based treatment, it is also anticipated that the benefit related to the use of docetaxel will not be of the same magnitude in all patients. For this reason, it will be extremely important to identify subgroups of patients deriving the highest benefit from the use of docetaxel. In the past few years, substantial progress has been made in the area of molecular biology, and several molecular markers that could predict the efficacy of docetaxel have been identified. The p53 gene mutations seem to be the most promising predictive markers because preclinical data suggest that taxane-induced apoptosis is p53 independent. Other molecular markers of potential interest are the microtubule-associated parameters, which might confer different degrees of sensitivity to a docetaxel-based therapy, depending on the pattern of expression.
Di Leo
Angelo
A
Jules Bordet Institute, Brussels-Belgium angelo.dileo@bordet.be
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005060:Europe; D005260:Female; D016158:Genes, p53 / Q000187:drug effects; D006801:Humans; D015337:Multicenter Studies as Topic; D017239:Paclitaxel / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D043823:Taxoids; D000077143:Docetaxel; C080625:taxane; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel