Tumor responses, adverse events and predictive factors for response in advanced breast cancer patients treated with combined chemotherapy with docetaxel and doxifluridine *
Purposes:It is reported that docetaxel（Doc）up-regulates thymidine phosphorylase（TP）expression and combined treatment with Doc and doxifluridine（5'DFUR）synergistically inhibits the growth of human breast cancer xenografts. We have conducted phase trials for combined chemotherapy with intravenous bi-weekly Doc and oral daily 5'DFUR in patients with advanced breast cancer. Tumor responses, adverse events and predictive factors for response were investigated in patients treated with this combined chemotherapy. Patients and Methods:A total of 25 patients with advanced breast cancer were treated with this combined therapy in our department. Expression levels of BRCA1 and TP were analyzed by immunohistochemistry in primary tumor samples. Relation among their levels and objective response（OR）rates were studied in 17 patients with assessable lesions. Results:１）Clinical study:the OR rate to this combined therapy was 68.1％（15/22, response could not be evaluated in three patients）. Grade 3 or grade 4 toxicity was observed in 20％（５/25）of the patients.２）Investigation on predictive factors:the OR rate was 92.3％(12/13）in BRCA1-positive and/or TP-positive tumors and ０％（０/４）in BRCA1-negative and TP-negative tumors, respectively（P＝0.003）. Multivariate analysis revealed that either BRCA1-positivity or TP-positivity is an independent predictive factor for objective response to this combined chemotherapy. Conclusion:These findings suggest that this combined therapy is active and safe in patients with advanced breast cancer and that the immunohistochemial analysis on BRCA1 and TP expression in primary tumors may be predictive for response to this combined therapy. (Accepted on October 17，2006)
