Navid Fariba, Furman Wayne L, Fleming Martin, Rao Bhaskar N, Kovach Sandra, Billups Catherine A, Cain Alvida M, Amonette Rex, Jenkins Jesse J, Pappo Alberto S
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Cancer. 2005 Feb 15;103(4):780-7. doi: 10.1002/cncr.20860.
It has been shown that induction high-dose interferon alpha-2b (IFN-alpha-2b) followed by maintenance therapy improves recurrence-free survival in adults with high-risk, resected melanoma. In this study, the feasibility and toxicity of this regimen were evaluated in newly diagnosed pediatric patients with Stage III melanoma involving regional lymph nodes.
Fifteen patients age <or=18 years with newly diagnosed Stage III melanoma were enrolled on an institutional protocol. Patients were treated with wide local excision, sentinel lymph node biopsy, lymph node dissection, and adjuvant biotherapy, consisting of induction therapy with 20 million IU/m2 per day IFN-alpha-2b intravenously 5 times per week for 4 weeks followed by maintenance therapy with IFN-alpha-2b 10 million IU/m2 per day subcutaneously 3 times per week for 48 weeks. Patients were monitored for toxicity and tumor recurrence.
All patients completed induction therapy, and nine patients completed maintenance therapy. Three patients currently are receiving maintenance, 2 patients developed recurrent disease on maintenance therapy, and 1 patient stopped maintenance therapy 5 weeks early. During induction therapy, Grade 3-4 toxicities included 14 episodes of neutropenia in 11 patients, 3 episodes of leukopenia in 2 patients, and 6 episodes of liver transaminase elevations in 5 patients. Dose modifications were required in four patients. During maintenance therapy, Grade 3-4 toxicities included 23 episodes of neutropenia in 10 patients and 2 episodes of liver transaminase elevations in 2 patients. Three patients required dose modifications. All toxicities were reversible with interruption or dose modification of therapy, and no patients were taken off study due to toxicity.
High dose IFN-alpha-2b for 4 weeks followed by a lower dose maintenance phase for 48 weeks was feasible in children with Stage III melanoma and was associated with tolerable toxicity.
已表明诱导性大剂量干扰素α-2b（IFN-α-2b）随后进行维持治疗可改善高危、已切除黑色素瘤成人患者的无复发生存率。在本研究中，评估了该方案在新诊断的伴有区域淋巴结转移的III期黑色素瘤儿科患者中的可行性和毒性。
15名年龄≤18岁新诊断为III期黑色素瘤的患者纳入一项机构方案。患者接受广泛局部切除、前哨淋巴结活检、淋巴结清扫及辅助生物治疗，包括诱导治疗，即每周5次静脉注射IFN-α-2b，每次2000万IU/m²，共4周，随后进行维持治疗，即每周3次皮下注射IFN-α-2b，每次1000万IU/m²，共48周。对患者进行毒性和肿瘤复发监测。
所有患者均完成诱导治疗，9名患者完成维持治疗。3名患者目前正在接受维持治疗，2名患者在维持治疗期间出现疾病复发，1名患者提前5周停止维持治疗。诱导治疗期间，3-4级毒性包括11名患者出现14次中性粒细胞减少、2名患者出现3次白细胞减少、5名患者出现6次肝转氨酶升高。4名患者需要调整剂量。维持治疗期间，3-4级毒性包括10名患者出现23次中性粒细胞减少和2名患者出现2次肝转氨酶升高。3名患者需要调整剂量。所有毒性通过中断治疗或调整剂量均可逆转，且无患者因毒性退出研究。
大剂量IFN-α-2b治疗4周后进行低剂量维持治疗48周，在III期黑色素瘤儿童患者中是可行的，且毒性可耐受。
