Duvic Madeleine, Apisarnthanarax Narin, Cohen Deborah S, Smith Terry L, Ha Chul S, Kurzrock Razelle
Division of Internal Medicine, Department of Dermatology, University of Texas M. D. Anderson Cancer Center, Houston 77030-4095, USA.
J Am Acad Dermatol. 2003 Jul;49(1):35-49. doi: 10.1067/mjd.2003.449.
Although cutaneous T-cell lymphoma (CTCL), including mycosis fungoides (MF) and Sézary syndrome, is often responsive to treatment, few current therapies increase survival or consistently induce durable remissions, especially in advanced disease.
In an effort to improve treatment efficacy and outcome in CTCL, a combined modality protocol using 3 to 4 consecutive phases of therapy was initiated in 1987 at M.D. Anderson Cancer Center, Houston, Tex.
During a period of 15 years between 1987 and 2001, 95 patients with early-stage (Ia-IIa, n = 50) and late-stage (IIb-IVb, n = 45) MF were treated with subcutaneous interferon-alpha and oral isotretinoin, followed by total-skin electron beam therapy, and long-term maintenance therapy with topical nitrogen mustard and interferon-alpha. Patients with late-stage (IIb-IVb) disease also received 6 cycles of combination chemotherapy before electron beam therapy.
Combined modality therapy yielded a response rate of 85% with a 60% complete response rate. Among 38 patients with early-stage disease and 18 patients with late-stage disease achieving complete response, 9 (24%) patients with early-stage MF and 3 (17%) patients with late-stage MF achieved sustained remissions lasting more than 5 years. The median disease-free survival (DFS) for early and late stages of disease was 62 and 7 months, with 5-year Kaplan-Meier estimated rates of 50% and 27%, respectively. Current median overall survival times on combined modality are 145 months for patients with early-stage disease and 36 months for those with late-stage disease. Death was attributable to CTCL disease in 17 (55%) of 31 cases. The Kaplan-Meier estimates for 5-year survival are 94% for early-stage and 35% for late-stage disease. Univariate survival analysis in this patient population reveals statistically significant associations of clinical stage with overall response rates (P =.02), DFS (P =.03), and overall survival (P <.0001); age with DFS (P =.001) and overall survival (P =.04); and T stage (P <.0001) and lactate dehydrogenase (P =.007) with overall survival. By multivariate analysis using a Cox proportional hazards model, only age was significantly associated with DFS (hazard ratio 2.9), and only stage with overall survival (hazard ratio 18.2).
This nonrandomized and uncontrolled CTCL study gives supportive evidence that this multiphased combined modality regimen is well tolerated and may yield higher response rates and DFS than total-skin electron beam therapy alone, but provides no evidence for a change in survival.
尽管皮肤T细胞淋巴瘤（CTCL），包括蕈样肉芽肿（MF）和塞扎里综合征，通常对治疗有反应，但目前很少有疗法能提高生存率或持续诱导持久缓解，尤其是在晚期疾病中。
为了提高CTCL的治疗效果和预后，1987年在德克萨斯州休斯顿的MD安德森癌症中心启动了一项使用3至4个连续治疗阶段的联合治疗方案。
在1987年至2001年的15年期间，95例早期（Ia-IIa，n = 50）和晚期（IIb-IVb，n = 45）MF患者接受皮下注射α干扰素和口服异维甲酸治疗，随后进行全身电子束治疗，以及外用氮芥和α干扰素的长期维持治疗。晚期（IIb-IVb）疾病患者在电子束治疗前还接受了6个周期的联合化疗。
联合治疗产生了85%的缓解率，完全缓解率为60%。在38例早期疾病患者和18例晚期疾病患者达到完全缓解中，9例（24%）早期MF患者和3例（17%）晚期MF患者实现了持续缓解超过5年。疾病早期和晚期的无病生存（DFS）中位数分别为62个月和7个月，5年Kaplan-Meier估计率分别为50%和27%。目前联合治疗的早期疾病患者的总生存中位数时间为145个月，晚期疾病患者为36个月。31例病例中有17例（55%）死亡归因于CTCL疾病。早期疾病和晚期疾病的5年生存Kaplan-Meier估计分别为94%和35%。该患者群体的单因素生存分析显示，临床分期与总缓解率（P =.02）、DFS（P =.03）和总生存（P <.0001）；年龄与DFS（P =.001）和总生存（P =.04）；以及T分期（P <.0001）和乳酸脱氢酶（P =.007）与总生存之间存在统计学显著关联。通过使用Cox比例风险模型的多因素分析，只有年龄与DFS显著相关（风险比2.9），只有分期与总生存相关（风险比18.2）。
这项非随机、无对照的CTCL研究提供了支持性证据，表明这种多阶段联合治疗方案耐受性良好，可能比单独的全身电子束治疗产生更高的缓解率和DFS，但没有提供生存改变的证据。
