Paclitaxel steady-state plasma concentration as a determinant of disease outcome and toxicity in lung cancer patients treated with paclitaxel and cisplatin.
Paclitaxel steady-state plasma concentration as a determinant of disease outcome and toxicity in lung cancer patients treated with paclitaxel and cisplatin.
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发表时间：
1999-04
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通讯作者：
E. Rowinsky;E. Rowinsky;Micheal Jiroutek;Philip Bonomi;David C Johnson;S D Baker
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作者：
E. Rowinsky;E. Rowinsky;Micheal Jiroutek;Philip Bonomi;David C Johnson;S D Baker
The principal purpose of this study was to evaluate relationships between paclitaxel plasma steady-state concentration (Css) and both disease outcome and toxicity in patients with non-small cell lung cancer (NSCLC) treated with paclitaxel and cisplatin in an Eastern Cooperative Oncology Group (ECOG) Phase III study E5592. Chemotherapy-naive patients with stage IIIb and IV NSCLC were randomized to treatment with either 75 mg/m2 cisplatin i.v. on day 1 and 100 mg/m2 etoposide i.v. on days 1-3 (EC arm) or 75 mg/m2 cisplatin i.v. combined with either a low dose of paclitaxel (135 mg/m2, 24-h i.v. infusion; PC arm) or a higher dose of paclitaxel (250 mg/m2 i.v., 24-h i.v. infusion) with granulocyte colony-stimulating factor (PCG arm). End-of-24-h-infusion paclitaxel concentrations, which have been demonstrated to be nearly equal to CssS on this schedule, were obtained during the first and second courses in patients on the PC and PCG arms. Relationships between the average paclitaxel Css (Css,avg) and the best response to treatment, time to treatment failure (TTF), survival, and worst grade of leukopenia and neurotoxicity were evaluated by univariate analysis. A multivariate model was used to assess the influence of paclitaxel Css in conjunction with other potentially relevant patient variables that may affect disease outcome, including the paclitaxel treatment arm, age, sex, performance status, weight loss during the previous 6 months, and disease stage. Paclitaxel Css in both courses 1 and 2 were obtained in 71 patients treated with PC and 75 patients treated with PCG. Although Css,avgS in patients treated with PC and PCG were significantly different (median, 0.32 versus 0.81 micromol/liter; P 135 mg/m2 in combination with cisplatin, although highe
