Velasquez W S, McLaughlin P, Tucker S, Hagemeister F B, Swan F, Rodriguez M A, Romaguera J, Rubenstein E, Cabanillas F
Section of Lymphoma, M.D. Anderson Cancer Center, Houston, TX.
J Clin Oncol. 1994 Jun;12(6):1169-76. doi: 10.1200/JCO.1994.12.6.1169.
This study attempted to determine the efficacy of the combination of etoposide (VP-16), methyl-prednisolone, and cytarabine (Ara-C) with or without cisplatin in relapsing and refractory adult lymphoma patients.
The first 63 patients were randomized to receive VP-16 40 mg/m2/d for 4 days, methylprednisolone 500 mg intravenously daily for 5 days, and Ara-C 2 g/m2 intravenously over 2 to 3 hours on day 5 with or without cisplatin 25 mg/m2 IV administered by 24-hour infusion for 4 days (ESHA +/- P). Markedly different responses between ESHA (33%) and ESHAP (75%) led to deletion of the ESHA arm. A total of 122 patients on the ESHAP regimen were studied.
Forty-five patients (37%) attained a complete remission (CR) and 33 (27%) attained a partial remission (PR), for a total response rate of 64%. The median duration of CR was 20 months, with 28% of remitters still in CR at 3 years. The overall median survival duration was 14 months; the survival rate at 3 years was 31%. Overall time to treatment failure (TTF) showed 10% of all patients to be alive and disease-free at 40 months. Response and survival rates were similar in patients with low-grade (n = 34), intermediate-grade (n = 67), transformed (n = 18), and high-grade (n = 3) lymphoma. The most significant factors for response and survival by multivariate analysis were the serum lactic dehydrogenase (LDH) level, tumor burden, and age (when analyzed as a continuous variable), while prior CR was highly significant by univariate analysis. A significant difference in survival was noted for patients with normal LDH levels and low- or intermediate-tumor burden or patients with low tumor burden and elevated LDH levels (55% 3-year survival rate) versus patients with elevated LDH levels and intermediate or high tumor burden (< 20%). Major toxicities included myelosuppression, with a median granulocyte count of 500/microL and platelet count of 70,000/microL.
ESHAP was found to be an active, tolerable chemotherapy regimen for relapsing and refractory lymphoma. Applying a prognostic model based on tumor burden and serum LDH level shows significant differences in survival in this patient population.
本研究旨在确定依托泊苷（VP - 16）、甲泼尼龙和阿糖胞苷（Ara - C）联合或不联合顺铂治疗复发和难治性成人淋巴瘤患者的疗效。
最初的63例患者被随机分为两组，一组接受依托泊苷40mg/m²/d，连用4天；甲泼尼龙500mg静脉注射，每日1次，连用5天；在第5天，阿糖胞苷2g/m²静脉滴注2至3小时，同时联合或不联合顺铂25mg/m²静脉滴注24小时，连用4天（ESHA±P）。ESHA组（33%）和ESHAP组（75%）的反应明显不同，因此取消了ESHA组。共对122例接受ESHAP方案治疗的患者进行了研究。
45例患者（37%）达到完全缓解（CR），33例（27%）达到部分缓解（PR），总缓解率为64%。CR的中位持续时间为20个月，3年时28%的缓解者仍处于CR状态。总体中位生存时间为14个月；3年生存率为31%。总体治疗失败时间（TTF）显示，40个月时所有患者中有10%存活且无疾病。低级别（n = 34）、中级别（n = 67）、转化型（n = 18）和高级别（n = 3）淋巴瘤患者的缓解率和生存率相似。多因素分析中，反应和生存的最显著因素是血清乳酸脱氢酶（LDH）水平、肿瘤负荷和年龄（作为连续变量分析），而单因素分析中既往CR具有高度显著性。LDH水平正常且肿瘤负荷低或中级别的患者，或肿瘤负荷低但LDH水平升高的患者，其生存率（55%的3年生存率）与LDH水平升高且肿瘤负荷中级或高级别的患者（< 20%）存在显著差异。主要毒性包括骨髓抑制，粒细胞计数中位数为500/μL，血小板计数中位数为70,000/μL。
ESHAP被发现是一种用于复发和难治性淋巴瘤的有效且可耐受的化疗方案。应用基于肿瘤负荷和血清LDH水平的预后模型显示，该患者群体的生存率存在显著差异。
