Georgiadis M S, Schuler B S, Brown J E, Kieffer L V, Steinberg S M, Wilson W H, Takimoto C H, Kelley M J, Johnson B E
National Cancer Institute-Navy Medical Oncology Branch, National Cancer Institute, Bethesda, MD, USA.
J Clin Oncol. 1997 Feb;15(2):735-43. doi: 10.1200/JCO.1997.15.2.735.
To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 96-hour continuous infusion in combination with cisplatin, to determine if the addition of granulocyte colony-stimulating factor (G-CSF) permits significant paclitaxel dose escalation, and to assess the toxicity and preliminary activity of this combination in patients with advanced lung cancer.
Fifty patients with untreated lung cancer were enrolled: 42 had advanced non-small-cell lung cancer (NSCLC) and eight had extensive-stage small-cell lung cancer (SCLC). Patients received paclitaxel doses of 100 to 180 mg/m2/96 hours and cisplatin doses of 60 to 80 mg/m2 as a single 30-minute bolus injection at the end of the paclitaxel infusion.
Two of six patients experienced dose-limiting neutropenia at a dose of paclitaxel 140 mg/m2/96 hours and cisplatin 80 mg/m2. With G-CSF support, one of three patients experienced both dose-limiting mucositis and fatal neutropenic sepsis at a dose of paclitaxel 180 mg/m2/96 hours and cisplatin 80 mg/m2. Significant peripheral neuropathy developed in five patients and occurred after six or more cycles of therapy. Thirty-three of 42 patients with NSCLC had measurable disease; the objective response rate was 55%, with two complete responses and 16 partial responses. For all 42 patients with NSCLC, the median time to progression and median survival duration were 5 months and 10 months, respectively. The actuarial 1-year survival rate was 41%. Of eight SCLC patients, four responded to therapy, and the median survival duration for all SCLC patients was 11 months.
The MTD without G-CSF is paclitaxel 120 mg/m2/96 hours and cisplatin 80 mg/m2, and the MTD with G-CSF is paclitaxel 160 mg/m2/96 hours and cisplatin 80 mg/m2. Infusional paclitaxel with cisplatin is well tolerated and active in patients with advanced NSCLC.
确定96小时持续输注紫杉醇联合顺铂的最大耐受剂量（MTD），确定添加粒细胞集落刺激因子（G-CSF）是否能使紫杉醇剂量显著增加，并评估该联合方案对晚期肺癌患者的毒性和初步活性。
纳入50例未经治疗的肺癌患者：42例为晚期非小细胞肺癌（NSCLC），8例为广泛期小细胞肺癌（SCLC）。患者接受的紫杉醇剂量为100至180mg/m²/96小时，顺铂剂量为60至80mg/m²，在紫杉醇输注结束时单次30分钟静脉推注。
6例患者中有2例在紫杉醇剂量为140mg/m²/96小时和顺铂剂量为80mg/m²时出现剂量限制性中性粒细胞减少。在G-CSF支持下，3例患者中有1例在紫杉醇剂量为180mg/m²/96小时和顺铂剂量为80mg/m²时出现剂量限制性粘膜炎和致命的中性粒细胞减少性败血症。5例患者出现显著的周围神经病变，且在六个或更多周期的治疗后发生。42例NSCLC患者中有33例有可测量的疾病；客观缓解率为55%，有2例完全缓解和16例部分缓解。对于所有42例NSCLC患者，中位进展时间和中位生存期分别为5个月和10个月。1年总生存率为41%。8例SCLC患者中有4例对治疗有反应，所有SCLC患者的中位生存期为11个月。
无G-CSF时的MTD为紫杉醇120mg/m²/96小时和顺铂80mg/m²，有G-CSF时的MTD为紫杉醇160mg/m²/96小时和顺铂80mg/m²。紫杉醇和顺铂联合输注对晚期NSCLC患者耐受性良好且有活性。
