Fetscher S, Brugger W, Engelhardt R, Kanz L, Hasse J, Frommhold H, Wenger M, Lange W, Mertelsmann R
Department of Internal Medicine, University of Freiburg Medical Center, Freiburg im Breisgau, Germany.
Ann Oncol. 1997 Jan;8(1):57-64. doi: 10.1023/a:1008209713568.
We conducted a phase I/II trial to assess the feasibility and activity of combination chemotherapy with etoposide, ifosfamide, cisplatin, and epirubicin in limited-stage (LS, stage I-IIIB) and extensive-stage (ES, stage IV) non-small-cell lung cancer (NSCLC). End-points were treatment-related morbidity and mortality, response rate, duration of response, and survival.
Chemotherapy followed by granulocyte colony-stimulating factor was given at a dose of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2), and epirubicin (50 mg/m2) (VIP-E) to 107 patients with NSCLC. Twenty-five patients with qualifying responses proceeded to high-dose chemotherapy with autologous peripheral blood stem cell transplantation after etoposide (1500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. RESULTS OF CONVENTIONAL-DOSE VIP-E: 35 of 102 (34%) evaluable patients responded (2 CR's, 33 PR's), 33/102 patients (33%) showed no change (NC); the remainder of patients progressed with therapy (PD). Objective response rate was 68% (4% CR, 64% PR) in LS-NSCLC and 23% (1.4% CR, 21.4% PR) in ES-NSCLC. Median duration of survival was 13 months in LS-NSCLC and 5.5 months in ES-NSCLC. Two-year survival was 26% in LS and 2% in ES-NSCLC. RESULTS OF HIGH-DOSE VIC-E: 23 of 24 evaluable patients improved or maintained prior responses (92%), I patient showed NC. Treatment mortality was 4%. Median duration of survival was 17 months in LS-NSCLC and 10 months in ES-NSCLC. Two-year survival was 30% in LS and 8% in ES-NSCLC.
Response-rates and survival after conventional-dose VIP-E chemotherapy are comparable to other published trials of combination chemotherapy in NSCLC. Toxicity and mortality is acceptable in limited stage, but unacceptably high in extensive stage NSCLC. Although better response-rates were achieved in the high-dose arm, they did not translate into improved survival. Most stage IV NSCLC-patients will neither benefit from VIP-E conventional dose, nor from VIC-E high dose chemotherapy. Whether selected LS-patients with partial or complete responses to VIP-E induction chemotherapy could benefit from dose intensification in an adjuvant or neo-adjuvant setting remains to be determined.
我们开展了一项I/II期试验，以评估依托泊苷、异环磷酰胺、顺铂和表柔比星联合化疗用于局限期（LS，I-IIIB期）和广泛期（ES，IV期）非小细胞肺癌（NSCLC）的可行性和活性。终点指标为治疗相关的发病率和死亡率、缓解率、缓解持续时间和生存率。
对107例NSCLC患者给予化疗后再使用粒细胞集落刺激因子，化疗方案为依托泊苷（500mg/m²）、异环磷酰胺（4000mg/m²）、顺铂（50mg/m²）和表柔比星（50mg/m²）（VIP-E）。25例缓解合格的患者在接受依托泊苷（1500mg/m²）、异环磷酰胺（12000mg/m²）、卡铂（750mg/m²）和表柔比星（150mg/m²）（VIC-E）预处理后进行高剂量化疗及自体外周血干细胞移植。常规剂量VIP-E的结果：102例可评估患者中有35例（34%）缓解（2例完全缓解，33例部分缓解），33/102例患者（33%）病情稳定（NC）；其余患者治疗进展（PD）。局限期NSCLC的客观缓解率为68%（4%完全缓解，64%部分缓解），广泛期NSCLC为23%（1.4%完全缓解，21.4%部分缓解）。局限期NSCLC的中位生存期为13个月，广泛期NSCLC为5.5个月。局限期NSCLC的两年生存率为26%，广泛期NSCLC为2%。高剂量VIC-E的结果：24例可评估患者中有23例改善或维持了先前的缓解（92%），1例病情稳定。治疗死亡率为4%。局限期NSCLC的中位生存期为17个月，广泛期NSCLC为10个月。局限期NSCLC的两年生存率为30%，广泛期NSCLC为8%。
常规剂量VIP-E化疗后的缓解率和生存率与其他已发表的NSCLC联合化疗试验相当。毒性和死亡率在局限期是可接受的，但在广泛期NSCLC中高得不可接受。尽管高剂量组获得了更好的缓解率，但并未转化为生存率的提高。大多数IV期NSCLC患者既不能从常规剂量的VIP-E中获益，也不能从高剂量的VIC-E化疗中获益。部分或完全缓解于VIP-E诱导化疗的特定局限期患者是否能在辅助或新辅助治疗中从剂量强化中获益仍有待确定。
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