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 <or= 70 mg/m2 in a 24-hour infusion can safely be combined with a 3-hour infusion of paclitaxel 175 mg/m2 and a 1-hour infusion of carboplatin AUC 5.
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 <or= 70 mg/m2 in a 24-hour infusion can safely be combined with a 3-hour infusion of paclitaxel 175 mg/m2 and a 1-hour infusion of carboplatin AUC 5.
Authors: Mark Andrew Dickson; Dana E Rathkopf; Richard D Carvajal; Steven Grant; John D Roberts; Joel M Reid; Matthew M Ames; Renee M McGovern; Robert A Lefkowitz; Mithat Gonen; Lauren M Cane; Heather J Dials; Gary K Schwartz Journal: Invest New Drugs Date: 2010-05-12 Impact factor: 3.850
Authors: Mark A Dickson; Manish A Shah; Dana Rathkopf; Archie Tse; Richard D Carvajal; Nian Wu; Robert A Lefkowitz; Mithat Gonen; Lauren M Cane; Heather J Dials; Gary K Schwartz Journal: Cancer Chemother Pharmacol Date: 2010-02-21 Impact factor: 3.333
Authors: N Nitta; A Sonoda; A Seko; S Ohta; Y Nagatani; K Tsuchiya; H Otani; T Tanaka; S Kanasaki; M Takahashi; K Murata Journal: Br J Radiol Date: 2009-12-17 Impact factor: 3.039