Held Gerhard, Schubert Joerg, Reiser Marcel, Pfreundschuh Michael
Innere Medizin I, Saarland University Medical School, Homburg, Germany.
Semin Hematol. 2006 Oct;43(4):221-9. doi: 10.1053/j.seminhematol.2006.07.003.
The introduction of the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen 30 years ago was the great breakthrough in the treatment of advanced-stage aggressive lymphomas. About 50% of all patients treated with CHOP achieved complete remission, and about one third experienced long-term disease-free survival and cure. Attempts to improve results by modifications of CHOP using escalated doses, additional drugs, or the alternative use of putatively non-cross-resistant chemotherapy regimens were not confirmed in randomized trials. With the availability of granulocyte colony-stimulating factor (G-CSF) and the tool of autologous stem cell support in the 1990s, dose escalation, dose densification (by interval reduction), or combinations thereof were pursued to increase dose intensity. While dose-escalation strategies, including high-dose approaches necessitating stem cell support, have not been demonstrated unequivocally yet to be superior to a baseline CHOP-21, dose-dense (biweekly) modifications improved the outcome of young and elderly patients with aggressive lymphomas compared to baseline CHOP-21. The challenges in the era of the monoclonal antibody rituximab are the identification of the ideal chemotherapy partner for rituximab both with respect to potential synergistic effects and to the lack of interference with its effector mechanisms. Finally, the issue of intensifying rituximab within such approaches must be addressed by appropriately designed randomized trials.
30年前CHOP（环磷酰胺、阿霉素、长春新碱和泼尼松）方案的引入是晚期侵袭性淋巴瘤治疗的重大突破。接受CHOP治疗的所有患者中约50%实现了完全缓解，约三分之一经历了长期无病生存并治愈。在随机试验中，通过增加剂量、添加其他药物或交替使用假定无交叉耐药的化疗方案来改进CHOP方案效果的尝试未得到证实。随着20世纪90年代粒细胞集落刺激因子（G-CSF）的出现以及自体干细胞支持手段的应用，人们采用剂量递增、剂量密集（通过缩短间隔时间）或两者结合的方法来提高剂量强度。虽然包括需要干细胞支持的高剂量方法在内的剂量递增策略尚未明确证明优于基线CHOP-21，但与基线CHOP-21相比，剂量密集（每两周一次）方案改善了侵袭性淋巴瘤年轻和老年患者的治疗结果。在单克隆抗体利妥昔单抗时代面临的挑战是，既要确定利妥昔单抗在潜在协同效应方面以及不干扰其效应机制方面的理想化疗搭档，最后，必须通过适当设计的随机试验来解决在这些方案中强化利妥昔单抗的问题。
