Riedel Richard F, Andrews Carolyn, Garst Jennifer, Dunphy Frank, Herndon James E, Blackwell Susan, Barbour Sally, Crawford Jeffrey
Ruth and Herman Albert Thoracic Oncology Program, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Thorac Oncol. 2007 Jun;2(6):520-5. doi: 10.1097/JTO.0b013e318060107c.
The impact of chemotherapy dose delivery has not been well studied in patients with non-small cell lung cancer (NSCLC). Overlapping hematologic toxicities commonly limit planned dose intensity of combination chemotherapy regimens. A phase II study investigating carboplatin and vinorelbine, supported by pegfilgrastim, in the treatment of patients with advanced NSCLC was performed.
Chemotherapy-naïve patients with locally advanced or metastatic NSCLC were treated with carboplatin area under the curve (AUC) 6 mg/ml per minute intravenously on day 1 and vinorelbine 30 mg/m2 intravenously on days 1 and 8 every 3 weeks for four planned cycles. Pegfilgrastim was administered on day 9 of each cycle as a 6-mg subcutaneous injection. The primary endpoint was incidence of cycle 1 febrile neutropenia. Secondary endpoints included incidence of grade 3/4 hematologic and nonhematologic toxicities, delivered dose intensity, and overall survival.
Thirty patients (21 men, 9 women) with a median age of 61 years (range, 43-79) were enrolled. Of 120 planned patient cycles, 101 (84%) were completed. There was one episode of cycle 1 febrile neutropenia. Overall response rate was 27%. Median dose delivered for vinorelbine was 17.2 mg/m2 per week, representing a delivered dose intensity of 86%. Median survival was 9.4 months (95% confidence interval: 6.1-18.0) with a 3-year survival rate of 20%.
This regimen of carboplatin and vinorelbine with pegfilgrastim support was associated with a low rate of febrile neutropenia and good maintenance of planned dose intensity. Although response and survival are similar to other chemotherapy regimens in advanced NSCLC, studies optimizing chemotherapy delivery in this setting may help inform treatment approaches in patients with earlier stage disease.
化疗剂量输送对非小细胞肺癌(NSCLC)患者的影响尚未得到充分研究。重叠的血液学毒性通常会限制联合化疗方案的计划剂量强度。开展了一项II期研究,调查培非格司亭支持下的卡铂和长春瑞滨治疗晚期NSCLC患者的疗效。
初治的局部晚期或转移性NSCLC患者,在第1天静脉注射卡铂,曲线下面积(AUC)为6mg/ml每分钟,在第1天和第8天静脉注射长春瑞滨30mg/m²,每3周进行4个计划周期。在每个周期的第9天给予培非格司亭6mg皮下注射。主要终点是第1周期发热性中性粒细胞减少的发生率。次要终点包括3/4级血液学和非血液学毒性的发生率、输送剂量强度和总生存期。
入组30例患者(21例男性,9例女性),中位年龄61岁(范围43 - 79岁)。在120个计划的患者周期中,101个(84%)完成。有1例第1周期发热性中性粒细胞减少。总缓解率为27%。长春瑞滨的中位输送剂量为每周17.2mg/m²,代表输送剂量强度为86%。中位生存期为9.4个月(95%置信区间:6.1 - ),3年生存率为20%。
这种卡铂和长春瑞滨联合培非格司亭支持的方案与发热性中性粒细胞减少率低和计划剂量强度的良好维持相关。尽管缓解率和生存期与晚期NSCLC的其他化疗方案相似,但在这种情况下优化化疗输送的研究可能有助于为早期疾病患者的治疗方法提供参考。 (注:原文中95%置信区间未完整给出上限数值)