Agelaki S, Bania H, Kouroussis C, Blazoyiannakis G, Souglakos J, Tsiafaki X, Harpidou A, Kalbakis K, Rapti A, Androulakis N, Sarra E, Georgoulias V, Papadakis E
Department of Medical Oncology, University General Hospital of Heraklion, Greece.
Oncology. 2001;60(3):235-41. doi: 10.1159/000055324.
Two parallel phase II trials were conducted in order to evaluate the efficacy and toxicity of vinorelbine-ifosfamide (VNB-IFX) and vinorelbine-carboplatin (VNB-C) combinations as salvage treatment in patients with advanced non-small cell lung cancer (NSCLC).
Patients failing platinum-based front-line chemotherapy were enrolled in the VNB-IFX trial while patients failing non-platinum-containing chemotherapy were treated with VNB-C. Twenty-nine patients were treated with VNB-IFX [median age: 59 years; performance status, PS (WHO) 0--1: 72% and disease stage IV: 79%] and 37 with VNB-C [median age: 61 years; PS (WHO) 0--1: 51% and stage IV: 84%]. Patients received vinorelbine 25 mg/m(2) i.v. on days 1 and 8 and ifosfamide 1.6 g/m(2) i.v. on days 8--10 with uroprotective mesna, in cycles of 28 days. G-CSF (5 microg/kg/day s.c.) was administered prophylactically on days 11--16 or until hematological recovery. The VNB-C regimen consisted of carboplatin 300 mg/m(2) on day 1 and vinorelbine 30 mg/m(2) on days 1 and 8 every 28 days.
Twenty-six patients were evaluable for response in the VNB-IFX trial and 29 in the VNB-C. Overall response rates (intent-to-treat analysis) were 3% (1 patient; duration of response: 3 months) for the VNB-IFX and 16% (median duration of response: 7.5 months) for the VNB-C combination. The median time to progression and survival for patients receiving VNB-IFX were 4.5 and 6 months (1-year survival: 19%), respectively; the corresponding values for VNB-C were 9.0 and 8.5 months (1-year survival: 38%). The median survival of patients achieving stable disease was 10 (VNB-IFX) and 14.5 (VNB-C) months. Grade 3--4 neutropenia occurred in 4 (13%) of the patients treated with VNB-IFX; all cases were complicated with fever. Grade 3--4 neutropenia was documented in 13 (35%) patients in the VNB-C trial; 6 (16%) developed neutropenic fever. There were no treatment-related deaths. Non-hematologic toxicity for the VNB-IFX and VNB-C regimens was mild with grade 2--3 peripheral neurotoxicity occurring in 3 (10%) and 7 (19%) patients, and grade 2--3 asthenia in 11 (38%) and 18 (48%) patients, respectively.
Both combinations were associated with a tolerable toxicity profile. VNB-C demonstrated notable activity in patients previously treated with a taxane-based regimen, whilst VNB-IFX failed to produce a significant response rate in patients treated with platinum-containing chemotherapy. Stabilization of disease was associated with a favorable survival in both studies.
进行了两项平行的II期试验，以评估长春瑞滨-异环磷酰胺（VNB-IFX）和长春瑞滨-卡铂（VNB-C）联合方案作为晚期非小细胞肺癌（NSCLC）患者挽救治疗的疗效和毒性。
接受铂类一线化疗失败的患者纳入VNB-IFX试验，而接受不含铂化疗失败的患者接受VNB-C治疗。29例患者接受VNB-IFX治疗[中位年龄：59岁；体能状态，PS（WHO）0-1：72%，疾病分期IV期：79%]，37例患者接受VNB-C治疗[中位年龄：61岁；PS（WHO）0-1：51%，IV期：84%]。患者在第1天和第8天静脉注射长春瑞滨25mg/m²，在第8-10天静脉注射异环磷酰胺1.6g/m²，并使用尿路保护剂美司钠，每28天为一个周期。在第11-16天预防性给予G-CSF（5μg/kg/天，皮下注射）或直至血液学恢复。VNB-C方案包括第1天给予卡铂300mg/m²，第1天和第8天给予长春瑞滨30mg/m²，每28天一次。
VNB-IFX试验中有26例患者可评估疗效，VNB-C试验中有29例。总体缓解率（意向性分析）VNB-IFX为3%（1例患者；缓解持续时间：3个月），VNB-C联合方案为16%（中位缓解持续时间：7.5个月）。接受VNB-IFX治疗的患者的中位疾病进展时间和生存期分别为4.5个月和6个月（1年生存率：19%）；VNB-C的相应值为9.0个月和8.5个月（1年生存率：38%）。疾病稳定的患者的中位生存期VNB-IFX为10个月，VNB-C为14.5个月。接受VNB-IFX治疗的患者中有4例（13%）发生3-4级中性粒细胞减少；所有病例均伴有发热。VNB-C试验中有13例（35%）患者记录到3-4级中性粒细胞减少；6例（16%）发生中性粒细胞减少性发热。无治疗相关死亡。VNB-IFX和VNB-C方案的非血液学毒性较轻，分别有3例（10%）和7例（19%）患者发生2-3级周围神经毒性，11例（38%）和18例（48%）患者发生2-3级乏力。
两种联合方案的毒性均可耐受。VNB-C在先前接受紫杉烷类方案治疗的患者中显示出显著活性，而VNB-IFX在接受含铂化疗的患者中未能产生显著的缓解率。在两项研究中，疾病稳定均与良好的生存相关。
