Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer.

Autor: George S; Cleveland Clinic Foundation, Cleveland, OH 44195, USA. georges2@ccf.org, Kasimis BS, Cogswell J, Schwarzenberger P, Shapiro GI, Fidias P, Bukowski RM
Jazyk: angličtina
Zdroj: Clinical lung cancer [Clin Lung Cancer] 2008 May; Vol. 9 (3), pp. 160-5.
DOI: 10.3816/CLC.2008.n.024
Abstrakt: Purpose: The aim of this study was to evaluate the safety and tolerability of escalating doses of flavopiridol/ paclitaxel/carboplatin in patients with advanced-stage non-small-cell lung cancer (NSCLC) as well as the pharmacokinetics and activity of flavopiridol when used in combination with paclitaxel/carboplatin.
Patients and Methods: Eligible patients aged 18-75 years with previously untreated stage IIIB/IV NSCLC received paclitaxel 175 mg/m2 over 3 hours followed by carboplatin area under the curve (AUC) 5 over 1 hour and flavopiridol 30-85 mg/m2 over 24 hours every 3 weeks for 3 cycles.
Results: Eighteen patients were enrolled at 4 sites in the United States and received flavopiridol 30 mg/m2 (n = 3), 50 mg/m2 (n = 6), 70 mg/m2 (n = 3), or 85 mg/m2 (n = 6). No dose-limiting toxicities (DLTs) occurred at the 50-mg/m2 or 70-mg/m2 dose levels. Two patients treated at the 85-mg/m2 dose level experienced cardiovascular events that did not meet the criteria for DLT but were fatal in 1 case, prompting no further flavopiridol dose escalations and establishment of 70 mg/m2 as the maximum tolerated dose. The most frequently reported adverse events across all dose levels combined were nausea (89%), asthenia (67%), and diarrhea (56%). Flavopiridol concentrations increased rapidly, reached a plateau, and showed a multiphasic decline after the 24-hour infusion. Of 12 patients evaluable for efficacy, 8 achieved a partial response, and 4 had stable disease.
Conclusion: Flavopiridol in doses
Databáze: MEDLINE
Externí odkaz: