Celsing F, Widell S, Merk K, Bernell P, Grimfors G, Hedlund A, Liliemark J, Svedmyr E, Osby E, Björkholm M
Department of Hematology and Infectious Diseases, Karolinska Hospital, Stockholm, Sweden.
Ann Oncol. 1998 Nov;9(11):1213-7. doi: 10.1023/a:1008446430765.
Second- and third-generation chemotherapy protocols for the treatment of aggressive non-Hodgkin's lymphomas (NHL) have considerable, and age-related, toxic effects. In addition, they do not seem to prolong overall survival in comparison to standard CHOP chemotherapy. In this phase II study we investigated the feasibility and efficacy of the addition of etoposide to the conventional CHOP regimen.
Toxicity and clinical efficacy were determined in 132 patients with previously untreated high-grade NHL. There were 51 patients in clinical stage I and II and 81 patients in stage III and IV, with a median age of 54 years (range 17-85). Patients received standard-dose CHOP plus etoposide 100 mg/m2 i.v. on day 1 and 200 mg/m2 p.o. on days 2-3.
The overall response rate was 84%, with 70% complete and 14% partial responses. The predicted three- and five-year survivals for the group as a whole were 60% and 53%, respectively, and the corresponding disease-free survivals for patients achieving complete remissions were 65% and 56%, respectively. Outcome was not different from that of CHOP-treated patients in a recently completed Nordic study performed during the same time period. Myelosuppression (WHO grade 3-4), observed in 87% of patients and infectious complications (WHO grade 3-4) in 33%, dominated the toxicity profile of this regimen. Fifty-seven of 92 complete responders (62%) received 6-8 CHOP-E cycles with no reductions in planned dose intensity. LDH level higher than normal, extranodal sites = 2, stage III-IV at diagnosis were all indicators of a poor survival.
We conclude that CHOP-E treatment is effective in high-grade NHL. However, mainly due to severe myelosuppression frequent schedule modifications were required and the results are not obviously superior to those of conventional CHOP.
用于治疗侵袭性非霍奇金淋巴瘤（NHL）的第二代和第三代化疗方案具有相当大的且与年龄相关的毒性作用。此外，与标准CHOP化疗相比，它们似乎并未延长总生存期。在这项II期研究中，我们调查了在传统CHOP方案中加入依托泊苷的可行性和疗效。
对132例既往未接受治疗的高级别NHL患者的毒性和临床疗效进行了测定。临床I期和II期患者有51例，III期和IV期患者有81例，中位年龄为54岁（范围17 - 85岁）。患者接受标准剂量CHOP加依托泊苷，第1天静脉注射100 mg/m²，第2 - 3天口服200 mg/m²。
总缓解率为84%，其中完全缓解率为70%，部分缓解率为14%。该组总体的预计3年和5年生存率分别为60%和53%，达到完全缓解的患者相应的无病生存率分别为65%和56%。结果与同期完成的一项北欧研究中接受CHOP治疗的患者的结果无差异。87%的患者出现骨髓抑制（WHO 3 - 4级），33%的患者出现感染并发症（WHO 3 - 4级），这在该方案的毒性特征中占主导地位。92例完全缓解者中有57例（62%）接受了6 - 8个CHOP - E周期治疗，计划剂量强度未降低。乳酸脱氢酶水平高于正常、结外部位≥2个、诊断时为III - IV期均为生存不良的指标。
我们得出结论，CHOP - E治疗在高级别NHL中是有效的。然而，主要由于严重的骨髓抑制，需要频繁调整治疗方案，且结果并不明显优于传统CHOP方案。
