Background: Cisplatin is widely used in combination chemotherapy against a variety of tumors; however, the optimal administration schedule of cisplatin is still controversial. To clarify the pharmacokinetic differences according to the administration schedules of cisplatin, we compared three different administration schedules of cisplatin such as single short-term infusion, daily short-term infusion and daily continuous infusion in combination with 5-fluorouracil. Preliminary clinical responses and toxicities were also investigated. Methods: A total of 12 courses in combination of cisplatin and 5-fluorouracil therapy was studied. The schedules of cisplatin tested were as follows: single short-term infusion (80 mg/m 2 , day 1,2 h div., n =4),daily short-term infusion (20mg/m 2 , days 1 to 5, 2 h div., n =4), daily continuous infusion (100 mg/m 2 , 120 h, n = 4). In all schedules, 5-fluorouracil was continuously administered at a dose of 800 mg/m 2/day on days 1 to 5. The area under the time-concentration curve (AUC) and the maximum concentration (C max ) of total and free Pt were investigated. Results: The highest AUC of total and free Pt and the lowest C max of free Pt were observed in the daily continuous infusion (total AUC; 162.53± 18.39~g h/ml, free AUC; 5.50±0.9~g h/ml, free Cmax; 0.07±0.01 Ilg /ml, mean ± SEM).Two patients in the single short-term infusion and one patient in the daily continuous infusion indicated partial responses clinically. No nephrotoxicity or ototoxicity was observed. All toxicities were mild and tolerable in all regimens; however, the incidence of GI toxicity in daily continuous infusion seemed to be relatively higher. Conclusions: Daily continuous infusion of cisplatin gave the best pharmacokinetic results and to evaluate the clinical advantage of this schedule a prospective randomized trial should be conducted with sufficient numbers of patients.
10750 Background: Capecitabine (C) is administrated with other drugs to improve response rate of single agent and to extend time to progression for MBC expecting up-regulation of thymidine phosphorylase activity. Conversely, administration of CPT-11 (TOP) against MBC is less common while superiority of combination therapy C and TOP is established in metastatic setting of colorectal cancer. Therefore a phase I clinical trial was conducted to determine the recommended dose (RD) of TOP administrated with fixed dose of C (1,657 mg/m2/day) against MBC pre-treated with antracycline and taxane. Methods: Five dose level of CPT-11 (80, 90, 100,110 and 120 mg/m2) on Day 1 and 15 and C (1,657 mg/m2/day) on Day 1–21 were given every 28 days. A standard “3+3” design is used and dose limiting toxicity is defined in cycle 1. Results: To date, five patients were enrolled from October 2005 to January 2006 and 8 cycles were administrated without grade 3–4 toxicities as followed: 3 pts in Level I (TOP: 80 mg/m2), 2 pts in Level II (TOP: 90mg/m2). 5 pts have archived a response: PR in 1, SD in 2. Conclusions: Combination therapy C and TOP against MBC pre-treated antracycline and taxane is well-tolerated. Enrollment will continue until the RD is identified for further phase II clinical trial. No significant financial relationships to disclose.
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