Hoffman P C, Masters G A, Drinkard L C, Krauss S A, Samuels B L, Golomb H M, Vokes E E
Department of Medicine, University of Chicago, IL, USA.
Ann Oncol. 1996 Mar;7(3):314-6. doi: 10.1093/oxfordjournals.annonc.a010578.
Ifosfamide and paclitaxel are active drugs in the management of non-small-cell lung cancer. We have performed a phase I study using a fixed dose of ifosfamide with escalating doses of paclitaxel, with G-CSF support, in an effort to determine the maximum tolerated dose (MTD) of paclitaxel in this combination, and to describe the dose-limiting toxicities of the combination at the recommended phase II dose of paclitaxel. We also studied the feasibility of delivering the paclitaxel as a one-hour infusion at the recommended phase II dose.
Thirty-one patients were treated, 25 with stage IV disease, and 6 with stage IIIB disease. Ifosfamide was administered at a dose of 1.6 g/m2 i.v. bolus daily x 3 days, with mesna uroprotection. Paclitaxel was administered as a 24-hour infusion at dose levels of 135, 170, 200, 250, and 300 mg/m2; six patients were treated with a one-hour infusion, at a dose of 250 mg/m2. G-CSF, 5 micrograms/kg, was administered subcutaneously on days 4 through 10, or until the absolute neutrophil count exceeded 4000/microliters. Cycles were repeated every 21 days.
The dose-limiting toxicity was granulocytopenia, which increased with increasing dose levels of paclitaxel. The MTD was 300 mg/m2 of paclitaxel, and the recommended phase II dose 250 mg/m2 administered as a 24-hour infusion. Other toxicities were generally mild, with only 5 patients demonstrating grade 3 neurotoxicity and 5 with grade 3 thrombocytopenia. Partial responses were seen in seven patients (23%), all in the 18 patients who received dose levels of 250 mg/m2 or higher.
Ifosfamide plus paclitaxel is an active treatment regimen in advanced non-small-cell lung cancer, and compares favorably with the results of cisplatin-based chemotherapy. A phase II study is in progress by the Cancer and Leukemia Group B, in an effort to better characterize the tolerance of the regimen, as well as its effect on tumor response and survival.
异环磷酰胺和紫杉醇是治疗非小细胞肺癌的有效药物。我们进行了一项I期研究，使用固定剂量的异环磷酰胺与递增剂量的紫杉醇，并给予粒细胞集落刺激因子（G-CSF）支持，以确定该联合方案中紫杉醇的最大耐受剂量（MTD），并描述在推荐的II期剂量下该联合方案的剂量限制性毒性。我们还研究了以推荐的II期剂量静脉输注1小时给予紫杉醇的可行性。
31例患者接受治疗，其中25例为IV期疾病，6例为IIIB期疾病。异环磷酰胺以1.6 g/m²静脉推注，每日1次，共3天，并给予美司钠尿路保护。紫杉醇以24小时输注方式给药，剂量水平分别为135、170、200、250和300 mg/m²；6例患者以250 mg/m²的剂量静脉输注1小时。在第4至10天皮下给予G-CSF，5微克/千克，或直至绝对中性粒细胞计数超过4000/微升。每21天重复一个周期。
剂量限制性毒性为粒细胞减少，随着紫杉醇剂量水平的增加而增加。MTD为紫杉醇300 mg/m²，推荐的II期剂量为250 mg/m²，以24小时输注方式给药。其他毒性一般较轻，只有5例患者出现3级神经毒性，5例出现3级血小板减少。7例患者（23%）出现部分缓解，均为接受250 mg/m²或更高剂量水平的18例患者。
异环磷酰胺加紫杉醇是晚期非小细胞肺癌的一种有效治疗方案，与基于顺铂的化疗结果相比具有优势。癌症与白血病B组正在进行一项II期研究，以更好地描述该方案的耐受性及其对肿瘤反应和生存的影响。
