Kay A C, Saven A, Carrera C J, Carson D A, Thurston D, Beutler E, Piro L D
Division of Hematology and Oncology, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
J Clin Oncol. 1992 Mar;10(3):371-7. doi: 10.1200/JCO.1992.10.3.371.
Because of the need to identify effective new agents in the treatment of non-Hodgkin's lymphoma and because of the high activity of the purine analog 2-chlorodeoxyadenosine (2-CdA) against chronic lymphocytic leukemia and hairy cell leukemia, a phase II trial of 2-CdA was initiated in patients with low-grade lymphocytic lymphomas.
Forty patients with low-grade lymphocytic lymphomas including diffuse small lymphocytic, follicular small-cleaved, and follicular mixed histologies were enrolled onto the study. Conventional therapies had failed in all patients, and six patients had lymph node biopsies showing evidence of histologic evolution to a higher-grade lymphoma. A total of 107 courses of 2-CdA were administered. There were 27 males and 13 females. The median age was 59 years (range, 37 to 80 years). Patients had received a median of three prior therapies (range, one to six therapies).
An overall response rate of 43% was achieved, with eight patients experiencing complete responses (CRs) and nine patients experiencing partial responses (PRs). The duration of responses ranged from 1 to greater than 33 months without maintenance therapy (median duration of response, 5 months). Histology and prior therapy history did not seem to correlate with responses. Significant toxicity was limited to bone marrow suppression; 18% of patients developed neutropenia, and 30% developed thrombocytopenia.
This phase II trial demonstrates that 2-CdA is an effective antilymphocyte, antineoplastic agent with significant activity as a single agent in patients with recurrent or refractory low-grade lymphocytic lymphoma. Responses were achieved with an acceptable toxicity profile. Further trials of this agent in previously untreated patients and in combination regimens are indicated and will be developed.
鉴于需要确定治疗非霍奇金淋巴瘤的有效新药物,且嘌呤类似物2-氯脱氧腺苷(2-CdA)对慢性淋巴细胞白血病和毛细胞白血病具有高活性,因此开展了一项针对低度淋巴细胞淋巴瘤患者的2-CdA II期试验。
40例低度淋巴细胞淋巴瘤患者入组本研究,包括弥漫性小淋巴细胞、滤泡性小裂细胞和滤泡性混合组织学类型。所有患者的常规治疗均失败,6例患者的淋巴结活检显示有组织学进展为高级别淋巴瘤的证据。共给予107个疗程的2-CdA。其中男性27例,女性13例。中位年龄为59岁(范围37至80岁)。患者既往接受治疗的中位数为3次(范围1至6次)。
总缓解率为43%,8例患者达到完全缓解(CR),9例患者达到部分缓解(PR)。在未进行维持治疗的情况下,缓解持续时间为1至超过33个月(中位缓解持续时间为5个月)。组织学类型和既往治疗史似乎与缓解情况无关。显著毒性仅限于骨髓抑制;18%的患者出现中性粒细胞减少,30%的患者出现血小板减少。
本II期试验表明,2-CdA是一种有效的抗淋巴细胞、抗肿瘤药物,作为单一药物对复发或难治性低度淋巴细胞淋巴瘤患者具有显著活性。缓解的同时毒性可接受。该药物在既往未治疗患者及联合治疗方案中的进一步试验是有必要的,且将会开展。