Bergmann L, Karakas T, Lautenschlager G, Jager E, Knuth A, Mitrou P S, Hoelzer D
Medical Clinic III, Hematology/Oncology, J.W. Goethe University, Frankfurt, Germany.
Ann Oncol. 1995 Dec;6(10):1019-24. doi: 10.1093/oxfordjournals.annonc.a059066.
Patients with high-grade non-Hodgkin's lymphoma (NHL) can potentially be cured by intensive chemotherapy. However, many patients still die of their disease, which underscores the need to define patient groups with different long-term prognoses and for more effective and possibly risk-adapted treatment approaches.
In this phase II study we investigated the feasibility and efficacy of a polychemotherapy consisting of 2 mg vincristine (V) on day 1, 25 mg/m2 doxorubicin (A) days 1-3, 800 mg cyclophosphamide (C) day 1, 60 mg/m2 prednisone (P) days 1-7 and 120 mg/m2 etoposide (E) days 1-3. This cycle (VACPE) was repeated on day 22 for up to 5 cycles in stages I-III and 6 cycles in stage IV, respectively, followed by consolidating radiotherapy in 38/73 patients. A total of 75 patients with high-grade NHLs according to the Kiel classification were eligible, and 73 patients are evaluable for response. The predominant histological subtypes were centroblastic, pleomorphic T-cell and large-cell anaplastic lymphomas, 60% of the patients presented with stage III/IV, 55% with a poor performance status (ECOG > or = 2), 53% with B symptoms and 60% with a LDH level >200 U/l.
57/73 patients achieved CR (78%), and the overall response rate (CR-PR) was 95%. The median observation time is 40 months (10+-74+). The 1-, 3- and 5-year overall survivals for the entire VACPE group were 79%, 64% and 61%, respectively. Forty-one patients are in ongoing CR with a continuous complete remission rate (CCR) of 67%. Fourteen of the 16 patients who relapsed (88%) did so within the first 24 months. The predicted 1-, 3- and 5-year DFS for those patients who achieved CR is 83%, 67% and 67%, respectively. The early mortality was 3/73 (4.1%). In patients with reduced performance status the overall survival (OS) (ECOG > or = 2) was significantly reduced, with a predicted 1-, 3- and 5-year survival of 62%, 49% and 49% versus 100%, 84% and 77% in patients with favorable performance status, respectively (p = 0.001). The predicted overall survival in stages III/IV is worse than in early stages with a 1-, 3- and 5-year probability of 73%, 52% and 52% versus 90%, 86% and 78%, respectively (p = 0.02). Comparison of patient groups with cumulative risk factors shows a significant decrease in overall survival. Especially in patients with 0-2 risk factors versus those presenting with >2 risk factors, there is a significantly better 3- and 5-year survival (p = 0.002). In contrast to overall survival, there were no differences between the listed risk groups concerning the disease-free survival of complete responders.
In conclusion, the VACPE regime is feasible and effective in high-grade NHLs and may also be administered on an outpatient basis. Despite encouraging data, however, a prospective randomized trial is warranted to define a possible superiority to standard CHOP. However, this regimen may be the basis for further randomized and risk adapted innovative approaches for high-grade NHLs.
高级别非霍奇金淋巴瘤（NHL）患者有可能通过强化化疗治愈。然而，许多患者仍死于该疾病，这突出表明需要明确具有不同长期预后的患者群体，并采用更有效且可能根据风险调整的治疗方法。
在这项II期研究中，我们调查了一种联合化疗方案的可行性和疗效，该方案包括第1天使用2mg长春新碱（V）、第1 - 3天使用25mg/m²阿霉素（A）、第1天使用800mg环磷酰胺（C）、第1 - 7天使用60mg/m²泼尼松（P）以及第1 - 3天使用120mg/m²依托泊苷（E）。此周期（VACPE）分别在第22天重复，I - III期最多重复5个周期，IV期重复6个周期，随后38/73例患者接受巩固性放疗。根据基尔分类，共有75例高级别NHL患者符合条件，73例患者可评估疗效。主要组织学亚型为中心母细胞性、多形性T细胞和大细胞间变性淋巴瘤，60%的患者为III/IV期，55%的患者体能状态较差（ECOG≥2），53%的患者有B症状，60%的患者乳酸脱氢酶水平>200U/L。
57/73例患者达到完全缓解（CR）（78%），总缓解率（CR + PR）为95%。中位观察时间为40个月（10±74+）。整个VACPE组的1年、3年和5年总生存率分别为79%、64%和61%。41例患者持续完全缓解，持续完全缓解率（CCR）为67%。16例复发患者中有14例（88%）在最初24个月内复发。达到CR的患者预计1年、3年和5年无病生存率分别为83%、67%和67%。早期死亡率为3/73（4.1%）。体能状态较差的患者（ECOG≥2）总生存期（OS）显著降低，预计1年、3年和5年生存率分别为62%、49%和49%，而体能状态良好的患者分别为100%、84%和77%（p = 0.001）。III/IV期患者的预计总生存期比早期患者差，1年、3年和5年生存率分别为73%、52%和52%，而早期患者分别为90%、86%和78%（p = 0.02）。对具有累积风险因素的患者组进行比较，总生存期显著降低。特别是0 - 2个风险因素的患者与>2个风险因素的患者相比，3年和5年生存率显著更高（p = 0.002）。与总生存期不同，在列出风险组的完全缓解者的无病生存期方面没有差异。
总之，VACPE方案在高级别NHL中可行且有效，也可在门诊实施。然而，尽管有令人鼓舞的数据，但仍需要进行前瞻性随机试验以确定其相对于标准CHOP方案的可能优势。然而，该方案可能是进一步针对高级别NHL进行随机和根据风险调整的创新方法的基础。
