Hohloch Karin, Zwick Carsten, Ziepert Marita, Hasenclever Dirk, Kaiser Ulrich, Engert Andreas, Höffkes Heinz-Gert, Kroschinsky Frank, Mesters Rolf, Feller Andreas C, Löffler Markus, Trümper Lorenz, Pfreundschuh Michael
Department of Hematology and Oncology, Georg August University, 37099 Göttingen, Germany.
Department Internal Medicine I, University of Saarland, 66421 Homburg/Saar, Germany.
Springerplus. 2014 Jan 3;3:5. doi: 10.1186/2193-1801-3-5.
Dose escalation and modification of CHOP has improved the prognosis of patients with aggressive lymphoma; even in the rituximab era, dose escalation for high-risk patients is exploited and frequently limited by drug toxicity. Idarubicin (Id) is a 4-demethoxy anthracycline analogue of daunorubicin with activity against lymphoma and has been reported to cause less cardiotoxicity than other anthracylines. The aim of this study was to replace doxorubicine with idarubicin in the CHOEP regimen and to find the maximum tolerable dose (MTD) of idarubicin based on hematotoxicity.
Between 11/96 and 09/98, 64 patients (pts) aged 18-75 yrs (pts. 18-60, LDH not elevated, >60 years all risk groups) with newly diagnosed aggressive lymphoma received 6 cycles of CIVEP-14 with an escalating dose of idarubicin, consisting of idarubicin (11-16 mg/m(2) d1) and standard doses of cyclophosphamide, vincristine, etoposide, and prednisone with G-CSF support.
55 pts (median age 56 yrs) were evaluable for a final analysis with a median observation time of 9.3 years. The CR-rate was 77.4% ; the 5 and 8-year-EFS rates were 46.4% (95%CI 32.5-60.3%) and 43.5% (29.4-57.6%), respectively, and the 5- and 8 yr OS rates were 64.6% (51.7-77.5%) and 59.9% (46.4-73.4%). 14/55 patients have died due to lymphoma progression, and 2/55 patients (3.6%) due to treatment related toxicity, 4/55 due to other causes (3 infections, 1 acute heart failure). In a matched pair analysis comparing CHOEP-14 and CIVEP-14, CIVEP-14 had a higher hematotoxicity with no significant differences in the event free and overall survival for the two regimens.
Thus, idarubicin cannot be used instead doxorubicin even if its dose is escalated to achieve similar hematotoxicity. Doxorubicin remains the standard anthracycline for the treatment of aggressive NHL.
CHOP方案的剂量递增和调整改善了侵袭性淋巴瘤患者的预后；即使在利妥昔单抗时代，高危患者的剂量递增仍在应用，但常因药物毒性而受限。伊达比星（Id）是柔红霉素的4-去甲氧基蒽环类类似物，对淋巴瘤有活性，据报道其心脏毒性低于其他蒽环类药物。本研究的目的是在CHOEP方案中用伊达比星替代多柔比星，并基于血液毒性确定伊达比星的最大耐受剂量（MTD）。
1996年11月至1998年9月期间，64例年龄在18 - 75岁（18 - 60岁患者，乳酸脱氢酶未升高；>60岁为所有风险组）新诊断的侵袭性淋巴瘤患者接受了6个周期的CIVEP - 14方案，伊达比星剂量递增，该方案包括伊达比星（11 - 16mg/m²，第1天）以及标准剂量的环磷酰胺、长春新碱、依托泊苷和泼尼松，并给予粒细胞集落刺激因子（G - CSF）支持。
55例患者（中位年龄56岁）可进行最终分析，中位观察时间为9.3年。完全缓解率为77.4%；5年和8年无事件生存（EFS）率分别为46.4%（95%CI 32.5 - 60.3%）和43.5%（29.4 - 57.6%），5年和8年总生存（OS）率分别为64.6%（51.7 - 77.5%）和59.9%（46.4 - 73.4%）。14/55例患者死于淋巴瘤进展，2/55例患者（3.6%）死于治疗相关毒性，4/55例患者死于其他原因（3例感染，1例急性心力衰竭）。在比较CHOEP - 14和CIVEP - 14的配对分析中，CIVEP - 14血液毒性更高，两种方案在无事件生存和总生存方面无显著差异。
因此，即使伊达比星剂量递增以达到相似的血液毒性，也不能用其替代多柔比星。多柔比星仍然是治疗侵袭性非霍奇金淋巴瘤的标准蒽环类药物。
