13017 Background: The mechanism of paclitaxel (PXL) resistance has been investigated. P-glycoprotein (P-gp) on cell membrane could be an important target for improving efficacy of PXL. Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. To determine safety and efficacy of PXL and TOR, we conducted a pharmacokinetic study for a combination chemo-endocrine treatment of PXL plus TOR for metastatic breast cancer. Methods: Patients with metastatic breast cancer, who were previously treated with a standard chemotherapy without PXL, were eligible. Patients received PXL 80 mg/m2(i.v.) weekly on days 1, 8, and 15 in a cycle. Concurrently, toremifene 120mg/body (p.o.) was given dairy from day 1–28 in a cycle. For pharmacokinetic study, single agent of PXL was initially administrated on day 1, 8, and 15. From day 18, TOR 120mg/body was given dairy. On day 22, PXL administration in second cycle was skipped. On day 32, blood samples were collected from the patients received PXL 80 mg/m2 + TOR 120 mg/day/body. Samples were analyzed by HPLC (Unisil Q 5CN). Response was evaluated by WHO criteria and adverse events were evaluated by NCI•CTC Ver.2. Results: Nineteen patients were enrolled. Out of 19, 15 patients had measurable disease, and 1 partial response, 8 stable disease, and 6 progressive disease were observed. The addition of TOR caused in no specific adverse events more than grade 3 and toxic profile in combination was similar that in PXL monotherapy. Pharmacokinetic profile of PXL was similar with/without TOR. In addition, Cmax of TOR was 1.85±0.71 mg/mL. Tmax was 2.9±1.8 hr were observed. AUC0–8 of TOR was not affected in the presence of PXL. AUC0- 8 of TOR-1, metabolite of TOR, also demonstrated the similar pharmacokinetic profile. Pharmacokinetic parameters of PXL did not reveal intra-patient variability in previously treated metastatic breast cancer patients. Conclusions: Pharmacokinetic profile in a combination of PXL and TOR was similar that in PXL monotherapy. The addition of TOR to PXL for previously treated metastatic breast cancer patients might be safety. No significant financial relationships to disclose.
Clinical Effect of Irinotecan in Advanced and Metastatic Breast Cancer Patients Previously Treated with Doxorubicin- and Docetaxel-containing Regimens