Creaven P J, Raghavan D, Perez R P, Pendyala L, Berghorn E J, Loewen G, Meropol N J
Department of Investigational Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Semin Oncol. 1996 Dec;23(6 Suppl 16):26-31.
In preparation for the design of phase II studies in lung cancer, low-dose carboplatin, fixed at a target area under the concentration-time curve (AUC) of 4.0 or 4.5 mg x min/mL, has been combined with escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in a series of studies to establish the maximum tolerated dose of the combination. In patients who had received prior chemotherapy, the maximum tolerated paclitaxel dose was 135 mg/m2 (carboplatin target AUC 4.0); the dose-limiting toxicity was febrile neutropenia. Without granulocyte colony-stimulating factor support in chemotherapy-naive patients (carboplatin target AUC 4.5), and with granulocyte colony-stimulating factor in chemotherapy-pretreated patients, the current paclitaxel dose is 290 mg/m2. The maximum tolerated dose has not been defined. In a study in which paclitaxel was given by 1-hour infusion with carboplatin (target AUC 4.5), a 205 mg/m2 dose was poorly tolerated. No evidence of pharmacokinetic interactions between paclitaxel and carboplatin was found. Twenty-one evaluable patients with lung cancer have been treated to date. There have been two partial responses, one minor response, and 10 patients with stable disease at paclitaxel doses of 100 to 270 mg/m2.
为开展肺癌II期研究做准备，在一系列研究中，固定低剂量卡铂的浓度-时间曲线下目标面积（AUC）为4.0或4.5mg·min/mL，并与递增剂量的紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）联合使用，以确定该联合用药的最大耐受剂量。在接受过先前化疗的患者中，紫杉醇的最大耐受剂量为135mg/m²（卡铂目标AUC为4.0）；剂量限制性毒性为发热性中性粒细胞减少。在未接受过化疗的患者中（卡铂目标AUC为4.5），化疗期间无粒细胞集落刺激因子支持，而在接受过化疗的患者中有粒细胞集落刺激因子支持的情况下，目前紫杉醇剂量为290mg/m²。最大耐受剂量尚未确定。在一项研究中，紫杉醇与卡铂（目标AUC为4.5）同时进行1小时输注，205mg/m²的剂量耐受性较差。未发现紫杉醇与卡铂之间存在药代动力学相互作用的证据。迄今为止，已有21例可评估的肺癌患者接受了治疗。在紫杉醇剂量为100至270mg/m²时，出现了2例部分缓解、1例轻微缓解，以及10例病情稳定的患者。
