Su Po-Jung, Chen Jen-Shi, Liaw Chuang-Chi, Chang Hsien-Kun, Wang Hung-Ming, Yang Tsia-Sheng, Lin Yung-Chang, Liau Chi-Ting, Yang Hsin-Yi, Yeh Kun-Yun, Ho Ming-Mo, Chang Nai-Jun, Wang Cheng-Hsu, Chang John Wen-Chen
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Chang Gung Med J. 2011 Sep-Oct;34(5):478-86.
The toxicity and efficacy of biochemotherapy with low-dose interleukin-2 for patients with metastatic malignant melanoma (MM) were studied.
Metastatic chemo-naive MM patients were given biochemotherapy (BCDT regimen) with carmustine (BCNU), cisplatin (CDDP), dacarbazine (DTIC), and tamoxifen and interleukin-2 (IL-2) 18 Million International Units in divided doses by subcutaneous injection three times a week for four weeks. BCDT consisted of BCNU (150 mg/m2, day l every 8 weeks), CDDP (25 mg/m2, days l-3 every 4 weeks), DTIC (220 mg/m2, days 1-3 every 4 weeks) and tamoxifen 10 mg twice a day. Treatment was repeated for a total of 6 cycles, or until disease progression or unbearable toxicity.
From Nov 2001 to July 2005, 40 patients (20 men; 20 women) were enrolled. Their median age was 54 years (range 22-79 years). Subtypes of melanoma included 23 (57.5%) acral lentiginous, 11 (27.5%) nodular, 1 (2.5%) mucosal, and 5 (12.5%) others. Grade 3-4 toxicities included neutropenia (27.5%), anemia (45%), and thrombocytopenia (40%). Constitutional IL-2 toxicities included indurate injection site (57.5%), fever (60%), chills (55%), itchy skin (42.5%), bone pain (32.5%) and myalgia (45%). Grade 1-2 hypotension was noted in 12.5% of patients. Eosinophilia (range 5% to 71%) was evident in 72.5% of patients. The response rate was 32.5% including 5% with a complete response, 27.5% with a partial response, and 17.5% with stable disease. The median progression-free survival was 6.2 months (95% CI: 2.99.6 months). The median overall survival was 11.3 months (95% CI: 7.015.6 months). Five patients (12.5%) who presented with oligo-metastasis achieved five-year survivals.
Our data demonstrated that low-dose IL-2 plus BCDT is tolerable. A durable response and long-term survival can be achieved in a small subgroup of patients.
研究低剂量白细胞介素-2生物化疗对转移性恶性黑色素瘤（MM）患者的毒性和疗效。
对未经化疗的转移性MM患者给予生物化疗（BCDT方案），包括卡莫司汀（BCNU）、顺铂（CDDP）、达卡巴嗪（DTIC）、他莫昔芬以及白细胞介素-2（IL-2）1800万国际单位，分剂量皮下注射，每周3次，共4周。BCDT方案包括BCNU（150mg/m²，每8周第1天）、CDDP（25mg/m²，每4周第1 - 3天）、DTIC（220mg/m²，每4周第1 - 3天）以及他莫昔芬10mg，每日2次。治疗共重复6个周期，或直至疾病进展或出现无法耐受的毒性。
2001年11月至2005年7月，纳入40例患者（20例男性；20例女性）。他们的中位年龄为54岁（范围22 - 79岁）。黑色素瘤亚型包括23例（57.5%）肢端雀斑样、11例（27.5%）结节型、1例（2.5%）黏膜型以及5例（12.5%）其他类型。3 - 4级毒性包括中性粒细胞减少（27.5%）、贫血（45%）以及血小板减少（40%）。全身性IL - 2毒性包括注射部位硬结（57.5%）、发热（60%）、寒战（55%）、皮肤瘙痒（42.5%）、骨痛（32.5%）以及肌痛（45%）。12.5%的患者出现1 - 2级低血压。72.5%的患者出现嗜酸性粒细胞增多（范围5%至71%）。缓解率为32.5%，包括5%的完全缓解、27.5%的部分缓解以及17.5%的病情稳定。中位无进展生存期为6.2个月（95%CI：2.9 - 9.6个月）。中位总生存期为11.3个月（95%CI：7.0 - 15.6个月）。5例（12.5%）出现寡转移的患者实现了5年生存。
我们的数据表明低剂量IL - 2联合BCDT是可耐受的。一小部分患者可实现持久缓解和长期生存。
