Strauss G M, Lynch T J, Elias A D, Jacobs C, Herbst R, Leong T, Lynch C, Kwiatkowski D J, Carey R W, Grossbard M L, Skarin A T
Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Semin Oncol. 1997 Aug;24(4 Suppl 12):S12-73-S12-80.
The primary objective of this study was to define the maximum tolerated dose and toxicity profile of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), given as a 24-hour infusion, in conjunction with ifosfamide/carboplatin/etoposide (ICE) chemotherapy in patients with advanced lung cancer. Paclitaxel was escalated from 75 to 225 mg/m2 in 25-mg/m2 increments. All patients received granulocyte colony-stimulating factor 5 microg/kg/d from day 4 until the neutrophil count was > or = 10,000/microL. The study population consisted of 41 patients with a median age of 60 years and a median follow-up of 20.7 months. Stage distribution included 5% stage IIIA, 46% stage IIIB, and 49% stage IV. Histology consisted of 61% adenocarcinoma, 12% squamous cell carcinoma, 10% large cell carcinoma, 15% small cell carcinoma, and 2% mixed. The predominant toxicity was hematologic; 63% of patients experienced grade 4 neutropenia and 49% developed grade 4 thrombocytopenia. Fever and neutropenia occurred in 34% of patients. Hematologic toxicity was, in all cases, short-term and reversible and was not dose related. With few exceptions, nonhematologic toxicity was not clinically important. Among 39 patients evaluable for response, 36% achieved a remission (8% complete, 28% partial, 41% had stable disease, and 23% experienced disease progression). Among 33 patients with non-small cell lung cancer, the response rate was 27% (one complete response, eight partial responses, 15 had stable disease, and nine had progressive disease). Among six patients with small cell carcinoma, the response rate was 83% (two complete responses, three partial responses, and one had stable disease). The median survival of all 41 patients was 13.6 months. Survival was almost identical between stage IIIA and stage IV subsets. We conclude that it is possible to safely administer full-dose single-agent paclitaxel with granulocyte colony-stimulating factor support in conjunction with full-dose ifosfamide/carboplatin/etoposide chemotherapy. While response rates observed were not particularly notable, median survival is considerably longer than that usually achieved with combination chemotherapy in advanced lung cancer.
本研究的主要目的是确定在晚期肺癌患者中，将紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）以24小时输注的方式与异环磷酰胺/卡铂/依托泊苷（ICE）联合化疗时的最大耐受剂量和毒性特征。紫杉醇剂量从75mg/m²开始，以25mg/m²的增量递增至225mg/m²。所有患者从第4天起接受粒细胞集落刺激因子5μg/kg/d，直至中性粒细胞计数≥10,000/μL。研究人群包括41例患者，中位年龄60岁，中位随访时间20.7个月。分期分布为ⅢA期5%，ⅢB期46%，Ⅳ期49%。组织学类型包括腺癌61%、鳞状细胞癌12%、大细胞癌10%、小细胞癌15%、混合性2%。主要毒性为血液学毒性；63%的患者出现4级中性粒细胞减少，49%的患者出现4级血小板减少。34%的患者发生发热和中性粒细胞减少。所有病例的血液学毒性均为短期且可逆，与剂量无关。除少数例外，非血液学毒性在临床上并不重要。在39例可评估疗效的患者中，36%达到缓解（8%完全缓解，28%部分缓解，41%病情稳定，23%病情进展）。在33例非小细胞肺癌患者中，缓解率为27%（1例完全缓解，8例部分缓解，15例病情稳定，9例病情进展）。在6例小细胞癌患者中，缓解率为83%（2例完全缓解，3例部分缓解，1例病情稳定）。41例患者的中位生存期为13.6个月。ⅢA期和Ⅳ期亚组的生存期几乎相同。我们得出结论，在粒细胞集落刺激因子支持下，将全剂量单药紫杉醇与全剂量异环磷酰胺/卡铂/依托泊苷联合化疗安全可行。虽然观察到的缓解率并不特别显著，但中位生存期比晚期肺癌联合化疗通常达到的生存期长得多。
