Cooper D L, Braverman I M, Sarris A H, Durivage H J, Saidman B H, Davis C A, Hait W N
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
Cancer. 1993 Apr 1;71(7):2335-41. doi: 10.1002/1097-0142(19930401)71:7<2335::aid-cncr2820710727>3.0.co;2-d.
Cyclosporine (cyclosporin A, CSA) prolongs the survival of transplanted organs by reducing the transcription of cytokines, especially interleukin-2, that are thought to mediate T-cell expansion and subsequent graft rejection. Recently, CSA has been suggested as a potentially effective agent in the treatment of T-cell neoplasms. As a result, a Phase II trial of CSA was done in patients with refractory T-cell lymphomas.
Patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who had disease progression after at least one previous therapy were eligible for participation. CSA was administered orally at a dose of 7.5 mg/kg twice daily, and the patients were followed for disease response and toxicity.
A total of 16 patients were treated. Five patients had PTCL, and 11 had CTCL. Most patients were pretreated extensively with chemotherapy and/or radiation therapy. No responses occurred in patients with PTCL. Two of 11 patients with CTCL responded to therapy. Both patients who responded to CSA had recurrent disease that approached baseline levels within 1 week of discontinuing therapy. A second response occurred in both patients after reinstitution of therapy. Although most patients were removed from the study because of disease progression, renal toxicity was significant.
Most patients with refractory T-cell lymphomas did not respond to CSA, suggesting that these malignancies are not interleukin-2 dependent or, alternatively, that CSA did not reach its intracellular target. In the two responding patients, the pattern of repeated rapid regression of disease after CSA administration and subsequent rapid recurrence after a temporary halt in therapy suggested that CSA was cytostatic rather than cytocidal or that the clinical remissions were mediated by the antiinflammatory effects of the drug.
环孢素（环孢菌素A，CSA）通过减少细胞因子的转录来延长移植器官的存活时间，尤其是白细胞介素-2，它被认为介导T细胞扩增及随后的移植物排斥反应。最近，CSA被认为是治疗T细胞肿瘤的一种潜在有效药物。因此，对难治性T细胞淋巴瘤患者进行了CSA的II期试验。
外周T细胞淋巴瘤（PTCL）或皮肤T细胞淋巴瘤（CTCL）患者，在至少一次先前治疗后疾病进展，符合参与条件。CSA口服给药，剂量为7.5mg/kg，每日两次，对患者进行疾病反应和毒性随访。
共治疗16例患者。5例为PTCL，11例为CTCL。大多数患者先前接受过广泛的化疗和/或放疗。PTCL患者无反应。11例CTCL患者中有2例对治疗有反应。对CSA有反应的两名患者均有复发性疾病，在停药1周内接近基线水平。再次治疗后两名患者均出现第二次反应。尽管大多数患者因疾病进展而退出研究，但肾毒性显著。
大多数难治性T细胞淋巴瘤患者对CSA无反应，提示这些恶性肿瘤不依赖白细胞介素-2，或者CSA未达到其细胞内靶点。在两名有反应的患者中，CSA给药后疾病反复快速消退，随后治疗暂时中断后迅速复发，这一模式表明CSA是细胞抑制性而非细胞杀伤性的，或者临床缓解是由药物的抗炎作用介导的。
