Fetscher S, Brugger W, Engelhardt R, Kanz L, Hasse J, Frommhold H, Lange W, Mertelsmann R
Department of Internal Medicine, University of Freiburg Medical Center, Freiburg im Breisgau, Germany.
Ann Oncol. 1999 May;10(5):561-7. doi: 10.1023/a:1026453922931.
We conducted a phase I-II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I-IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC).
Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. RESULTS OF STANDARD-DOSE VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC. RESULTS OF HIGH-DOSE VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC.
Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR > 2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.
我们开展了一项I-II期试验，以评估依托泊苷、异环磷酰胺、顺铂或卡铂及表柔比星联合化疗方案用于局限期（LD，I-IIIB期）和广泛期（ED，IV期）小细胞肺癌（SCLC）的可行性及活性。
100例SCLC患者接受了由依托泊苷（500mg/m²）、异环磷酰胺（4000mg/m²）、顺铂（50mg/m²）和表柔比星（50mg/m²）组成的标准剂量化疗（SDC）（VIP-E方案），随后给予粒细胞集落刺激因子（G-CSF）。30例对VIP-E方案有合格反应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方案）预处理后，进行高剂量化疗（HDC）及自体外周血干细胞移植（PBSCT）。标准剂量VIP-E方案的结果：97例患者可评估疗效。局限期SCLC的客观缓解率为81%（完全缓解率33%，部分缓解率48%；不包括手术完全缓解的患者），广泛期SCLC为77%（完全缓解率18%，部分缓解率58%）。SDC的治疗相关死亡率为2%。另外2例SCLC完全缓解的患者发生了继发性非小细胞肺癌（NSCLC），二者均通过手术治愈。局限期SCLC的中位生存期为19个月，广泛期SCLC为6个月。局限期SCLC的5年生存率为36%，广泛期SCLC为0%。高剂量VIC-E方案的结果：HDC在16%的广泛期患者和58%的局限期患者中可行。所有接受HDC的患者（n = 30）病情改善或维持了之前的反应。4例患者死于早期治疗相关并发症（治疗相关死亡率13%）。另外有2例SCLC完全缓解的患者发生了继发性恶性肿瘤（食管癌、继发性慢性粒细胞白血病）。局限期SCLC的中位生存期为26个月，广泛期SCLC为8个月。局限期SCLC的5年生存率为50%，广泛期SCLC为0%。
尽管缓解率较高，但广泛期SCLC患者接受VIP-E SDC和VIC-E HDC后的生存期并不优于毒性较低的传统方案。这些方案在局限期SCLC中实现的高5年生存率可能既反映了患者选择（既往手术切除患者比例高），也反映了我们的化疗方案联合放疗的高活性。需要开展一项研究，比较同时使用放疗和化疗的方案以及其他剂量递增形式的SDC与HDC，以进一步明确这种治疗方式在SCLC中的作用。鉴于在我们的研究中，完全缓解超过2年的患者中观察到较高的继发性恶性肿瘤发生率，对这些肿瘤进行密切随访和早期治疗可能有助于维持SCLC患者的总体生存期。
