Visceral disease in patients with metastatic breast cancer: efficacy and safety of treatment with ixabepilone and other chemotherapeutic agents.
Patients with metastatic breast cancer (MBC) have poor prognoses and 5-year survival rates of approximately 20%. The site(s) and degree of metastatic dissemination are among the principal prognostic factors for patients with MBC. Patients with visceral metastases to the liver and/or lung have a very poor prognosis. Although good performance status, restricted disease dissemination, and limited extent of metastatic infiltration are associated with higher responses to chemotherapy, responses are generally short lived, with rapid disease progression after treatment failure. Thus, novel strategies for the management of patients with MBC with visceral disease are urgently needed. We have analyzed outcomes of trials that evaluated various chemotherapeutic agents as monotherapy or in combination with capecitabine in patients with MBC with primary visceral disease involvement. Treatment with microtubule inhibitors such as paclitaxel, docetaxel, and albumin-bound paclitaxel, generally administered in earlier lines of treatment, resulted in comparable responses. Lower response rates (RRs) were reported with other agents such as capecitabine, vinorelbine, and gemcitabine. Adverse events consistent with known toxicities of each agent were observed in the selected trials and related to dose and administration schedule. The epothilone B analogue ixabepilone has demonstrated clinical efficacy and manageable safety in populations of heavily pretreated patients with MBC with high visceral disease burdens to liver and/or lung (61%-86% of patients). Objective RRs ranging from 12% to 57% have been reported for ixabepilone, as monotherapy and in combination with capecitabine, depending on degree of pretreatment. Responses to ixabepilone in patients with visceral metastases were comparable to those observed in overall study patient populations.
Sarah Cannon Research Institute, Nashville, TN 37203, USA. dyardley@tnonc.com
Denise A
DA
Yardley
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D034261:Epothilones / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D014781:Viscera / Q000473:pathology
D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone