Department of Dermatology, University of Pittsburgh, 200 Lothrop Street, Presby South Tower, Suite 3880, Pittsburgh, PA 15213, USA.
Br J Dermatol. 2012 Jul;167(1):194-7. doi: 10.1111/j.1365-2133.2012.10905.x.
Romidepsin is a structurally unique histone deacetylase inhibitor approved by the U.S. Food and Drug Administration for therapy of relapsed or refractory cutaneous T-cell lymphoma (CTCL). Localized electron beam radiation therapy (LEBT) is standard practice in the care of patients with chronically traumatized and painful lesions. Combination therapy of those two modalities may be beneficial for the therapy of CTCL.
To report observations on supportive LEBT utilized for isolated refractory lesions in patients on romidepsin.
Observations were made during a phase II clinical trial sponsored by the National Cancer Institute (NCI-1312) examining the efficacy of romidepsin for patients with relapsed, refractory or advanced CTCL, stage IB-IVA mycosis fungoides (MF) or Sézary syndrome. Skin responses were assessed by evaluation of five target lesions only. Patients with objective clinical responses in target lesions who had symptomatic nontarget lesions were allowed limited LEBT to isolated lesions for symptomatic relief. Patients who received localized radiation were not considered complete responders at any point.
Five patients with advanced MF (three stage IIB and two stage IVA2) received LEBT to symptomatic nontarget lesions while on a protocol with romidepsin. None of these patients experienced additional or unexpected toxicity. Four of the five patients demonstrated fast and durable responses. We noted that significantly lower than standard doses of LEBT effectively treated symptomatic lesions in these patients.
LEBT demonstrated significant responses at very low doses without additional toxicity in patients on protocol treatment with the histone deacetylase inhibitor romidepsin. This merits formal investigation in a clinical trial for potential synergy in patients with CTCL.
罗米地辛是一种结构独特的组蛋白去乙酰化酶抑制剂，已获美国食品药品监督管理局批准用于治疗复发性或难治性皮肤 T 细胞淋巴瘤（CTCL）。局部电子束放射治疗（LEBT）是治疗慢性创伤性和疼痛性病变患者的标准方法。这两种方法的联合治疗可能对 CTCL 的治疗有益。
报告在接受罗米地辛治疗的患者中，对孤立性难治性病变进行支持性 LEBT 治疗的观察结果。
在一项由美国国立癌症研究所（NCI-1312）赞助的 II 期临床试验中观察到这些结果，该试验检查了罗米地辛对复发性、难治性或晚期 CTCL、IB-IVA 期蕈样真菌病（MF）或 Sézary 综合征患者的疗效。仅通过评估五个靶病变来评估皮肤反应。在靶病变中有客观临床反应且有症状非靶病变的患者，允许对孤立性病变进行有限的 LEBT 治疗以缓解症状。在任何时候，接受局部放疗的患者均不被认为是完全缓解者。
五名患有晚期 MF（三名 IIB 期和两名 IVA2 期）的患者在接受罗米地辛治疗方案的同时，对有症状的非靶病变进行了 LEBT。这些患者均未出现额外或意外的毒性。五名患者中的四名迅速且持久地缓解。我们注意到，这些患者接受的 LEBT 剂量明显低于标准剂量，但对症状性病变的治疗效果显著。
在接受组蛋白去乙酰化酶抑制剂罗米地辛治疗方案的患者中，LEBT 以非常低的剂量表现出显著的反应，且没有额外的毒性。这值得在临床试验中进行正式研究，以探讨其在 CTCL 患者中的潜在协同作用。
