Strauss G M, Lynch T J, Elias A D, Jacobs C, Kwiatkowski D J, Shulman L N, Carey R W, Grossbard M L, Jauss S, Sugarbaker D J
Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Semin Oncol. 1995 Aug;22(4 Suppl 9):70-4.
A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.
开展了一项I期研究，以确定异环磷酰胺/卡铂/依托泊苷/紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）（ICE-T）方案用于晚期肺癌时的最大耐受剂量和毒性特征。该化疗方案采用24小时持续输注紫杉醇，并联合全剂量ICE化疗及生长因子支持。紫杉醇剂量从75mg/m²逐步递增至225mg/m²。截至目前，已有34例患者入组该研究。由于血液学剂量限制性毒性定义为中性粒细胞减少和/或血小板减少持续超过7天，因此没有患者出现方案所定义的剂量限制性毒性。尽管如此，仍观察到明显的血液学毒性。总体而言，26%的患者出现发热伴中性粒细胞减少，56%的患者出现4级中性粒细胞减少，26%的患者出现4级血小板减少。所有病例中，血液学毒性均为短期且可逆。虽然经常观察到3级和4级骨髓抑制，但与剂量无关（就紫杉醇剂量而言）。非血液学毒性也与剂量无关，且仅有少数例外情况具有临床意义。在可评估疗效的27例患者中，41%获得客观缓解，其中15%为完全缓解。5例小细胞肺癌患者均有反应（包括2例完全缓解）。在22例非小细胞肺癌患者中，27%获得客观缓解（也包括2例完全缓解）。本研究结果表明，在生长因子支持下，有可能安全地将全剂量单药紫杉醇与全剂量ICE化疗联合应用。我们很快将启动一项II期研究，在晚期肺癌中采用225mg/m²的紫杉醇进行24小时持续输注的ICE-T方案。我们还将开展一项ICE-T的I期研究，采用3小时持续输注紫杉醇的方式。
