Itoh K, Ohtsu T, Fukuda H, Sasaki Y, Ogura M, Morishima Y, Chou T, Aikawa K, Uike N, Mizorogi F, Ohno T, Ikeda S, Sai T, Taniwaki M, Kawano F, Niimi M, Hotta T, Shimoyama M, Tobinai K
Division of Hematology and Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Ann Oncol. 2002 Sep;13(9):1347-55. doi: 10.1093/annonc/mdf287.
CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) is accepted as the best available standard treatment for first-line chemotherapy in aggressive non-Hodgkin's lymphoma (NHL). However, the therapeutic efficacy of CHOP remains unsatisfactory, particularly in high-intermediate risk and high risk patients, and a new strategy is warranted in this patient population. The aim of the present study was to explore a suitable therapeutic-intensified regimen for the treatment of aggressive NHL.
Between May 1995 and July 1998, a total of 70 patients with high-intermediate risk or high risk aggressive NHL, according to the International Prognostic Index, were enrolled and randomly assigned to receive either eight cycles of standard CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 2 weeks, or six cycles of dose-escalated CHOP (cyclophosphamide 1500 mg/m(2), doxorubicin 70 mg/m(2), vincristine 1.4 mg/m(2) and prednisolone 100 mg for 5 days) every 3 weeks. Lenograstim (glycosylated rHuG-CSF), at a dose of 2 micro g/kg/day s.c., was administered daily from day 3 until day 13 with biweekly CHOP and until day 20 with the dose-escalated CHOP. The primary endpoint was complete response rate.
The complete response rate was 60% [21 of 35; 95% confidence interval (CI) 42% to 76%] with biweekly CHOP and 51% (18 of 35; 95% CI 34% to 69%) with dose-escalated CHOP. The major toxicity was grade 4 neutropenia and was more frequent in the dose-escalated CHOP arm (86%) than in the biweekly CHOP arm (50%). Grade 4 thrombocytopenia was also more frequent in the dose-escalated CHOP arm (20%) than the biweekly CHOP arm (3%). Non-hematological toxicities were acceptable in both arms. One treatment-related death (due to cardiac arrhythmia) was observed in a dose-escalated CHOP patient. Progression-free survival at 3 years was 43% (95% CI 27% to 59%) in the biweekly CHOP arm and 31% (95% CI 16% to 47%) in the dose-escalated CHOP arm. Although seven patients were deemed ineligible by central review of the pathological diagnosis, the results for both eligible and all enrolled patients were similar.
Similar complete response rates and progression-free survival rates, but lower toxicity, indicated that biweekly CHOP was superior to dose-escalated CHOP in the treatment of aggressive NHL. Based on these results, the Lymphoma Study Group of the Japan Clinical Oncology Group is conducting a randomized phase III study comparing biweekly CHOP with standard CHOP in newly diagnosed patients with advanced-stage aggressive NHL.
CHOP（环磷酰胺、阿霉素、长春新碱和泼尼松）被公认为侵袭性非霍奇金淋巴瘤（NHL）一线化疗的最佳可用标准治疗方案。然而，CHOP的治疗效果仍不尽人意，尤其是在高中危和高危患者中，因此需要针对这一患者群体制定新的治疗策略。本研究的目的是探索一种适合治疗侵袭性NHL的强化治疗方案。
1995年5月至1998年7月，根据国际预后指数，共纳入70例高中危或高危侵袭性NHL患者，并随机分为两组，一组每2周接受8个周期的标准CHOP方案（环磷酰胺750mg/m²、阿霉素50mg/m²、长春新碱1.4mg/m²和泼尼松龙100mg，连用5天），另一组每3周接受6个周期的剂量递增CHOP方案（环磷酰胺1500mg/m²、阿霉素70mg/m²、长春新碱1.4mg/m²和泼尼松龙100mg，连用5天）。从第3天至第13天，每2周CHOP方案组每日皮下注射来格司亭（糖基化重组人粒细胞集落刺激因子），剂量为2μg/kg/天；剂量递增CHOP方案组则至第20天。主要终点为完全缓解率。
每2周CHOP方案组的完全缓解率为60%（35例中的21例；95%置信区间[CI]为42%至76%），剂量递增CHOP方案组为51%（35例中的18例；95%CI为34%至69%）。主要毒性为IV级中性粒细胞减少，在剂量递增CHOP方案组中更常见（86%），高于每2周CHOP方案组（50%）。IV级血小板减少在剂量递增CHOP方案组中也更常见（20%），高于每2周CHOP方案组（3%）。两组的非血液学毒性均可接受。在剂量递增CHOP方案组中有1例患者（因心律失常）发生与治疗相关的死亡。每2周CHOP方案组3年无进展生存率为43%（95%CI为27%至59%），剂量递增CHOP方案组为31%（95%CI为16%至47%）。尽管经中心病理诊断复查后有7例患者被判定为不符合入组标准，但符合标准患者和所有入组患者的结果相似。
相似的完全缓解率和无进展生存率，但毒性更低，表明每2周CHOP方案在治疗侵袭性NHL方面优于剂量递增CHOP方案。基于这些结果，日本临床肿瘤学会淋巴瘤研究组正在进行一项随机III期研究，比较每2周CHOP方案与标准CHOP方案在新诊断的晚期侵袭性NHL患者中的疗效。
