Cyclophosphamide and Cisplatin Compared with Paclitaxel and Cisplatin in Patients with Stage III and Stage IV Ovarian Cancer

Abstract

Incorporating paclitaxel into first-line therapy improves the duration of progression-free survival and of overall survival in women with incompletely resected stage III and stage IV ovarian cancer.

Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine

“…(The United States Adopted Name Council has given the name paclitaxel to refer to the registered trade name Taxol; Bristol-Myers Squibb.) Paclitaxel has become a very important drug in the treatment of cancer (20,21), and it is also a very good substrate of P-glycoprotein, as was shown by in vitro transport studies in polarized monolayers of an MDR1-transfected pig kidney epithelial cell line (LLC-PK1; unpublished results). Our pilot experiments confirmed an earlier study, reporting that the concentration of paclitaxel in plasma of mice remained very low after oral drug administration (22).…”

Therapy of ovarian cancers with targeted cytotoxic analogs of bombesin, somatostatin, and luteinizing hormone-releasing hormone and their combinations

“…Advanced epithelial ovarian cancer is currently treated by cytoreductive surgery and chemotherapy (2). The preferred systemic treatment for patients with advanced-stage disease is the paclitaxel͞carboplatin combination, which produces a significant improvement in both progression-free and overall survival rates (3). However, after an initial response (4), patients eventually experience a recurrence of the disease (5) due to secondary induction of chemoresistance of the cancer cells.…”

Aurora kinase inhibitor VE 465 synergistically enhances cytotoxicity of carboplatin in ovarian cancer cells through induction of apoptosis and downregulation of histone 3

“…Despite extensive efforts to prolong patient survival, the overall survival rates for patients with advanced epithelial ovarian cancer have improved only slightly during the past 20 years. [1][2][3] Combination chemotherapy consisting of a platinum and paclitaxelis the current standard of care. Although the cancer initially responds to this treatment in most patients, the disease usually relapses because of acquired resistance to the chemotherapeutic agents.…”

“…A better understanding of the molecular aspects of ovarian tumorigenesis and identification of novel molecular targets may lead to new and more effective therapeutic strategies. [2][3][4][5] Human Aurora kinases A, B and C are known to be involved in the regulation of centrosome function, bipolar spindle assembly and chromosome segregation processes. 6 Ectopic overexpression of Aurora kinases in mammalian cells induces centrosome amplification, 7 chromosome instability, 8 oncogenic transformation 8 and chemoresistance.…”