Department of Melanoma and Renal Cancer, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Eur J Cancer. 2011 Jul;47(10):1498-503. doi: 10.1016/j.ejca.2011.03.019. Epub 2011 Apr 13.
High-dose Interferon-α-2b (HD-IFN) is an adjuvant treatment for melanoma. However, clinical trials for HD-IFN have not been reported in acral melanoma (AM), the predominant subtype of cutaneous melanoma in Asian population.
Patients with resected high-risk (stage IIb-IIIc) AM were randomly assigned to a regimen of 4-week (arm A: 15 × 10(6)U/m(2)d1-5/w × 4w) or 1-year adjuvant HD-IFN (arm B: 15 × 10(6)U/m(2)d1-5/w × 4w+9 × 10(6)Utiw × 48w), respectively. The endpoints were relapse-free survival (RFS), overall survival (OS) and toxicities.
A total of 158 patients were enrolled in this study and 147 patients were eligible for survival analysis. With a median follow-up of 36.1 months, median RFS for arm A and arm B were 17.9 months and 22.5 months, respectively (P=0.72). Stratified analysis showed that RFS curves of patients in stage IIIb-IIIc were statistically different between arm A and arm B (P=0.02). The median RFS of patients with more nodal metastases (n⩾3) was shorter (P=0.004) in arm A (3.3 months) than that in arm B (11.9 months). Grade 1/2 adverse effects were observed in both groups. However, patients in arm B showed higher incidence of reversible Grade 3/4 hepatotoxicity (P=0.03).
The induction dose of 15 × 10(6)U/m(2) and the maintenance dose of 9 × 10(6)U were tolerable, which may be the optional dose intensity for adjuvant IFN-α-2b therapy in Chinese high risk AM population. No statistical significance was detected in RFS between the 4-week and 1-year regimen while a 1-year regimen may show clinical benefits in patients with stage IIIb-IIIc AM or with ≥ 3 nodal metastases.
高剂量干扰素-α-2b（HD-IFN）是黑色素瘤的辅助治疗方法。然而，在亚洲人群中皮肤黑色素瘤的主要亚型肢端黑色素瘤（AM）中，尚未报道 HD-IFN 的临床试验。
对接受高风险（IIb 期-IIIc 期）AM 切除术的患者进行随机分组，分别接受 4 周方案（A 组：15×10(6)U/m(2)d1-5/w×4w）或 1 年辅助 HD-IFN（B 组：15×10(6)U/m(2)d1-5/w×4w+9×10(6)Utiw×48w）治疗。终点是无复发生存率（RFS）、总生存率（OS）和毒性。
本研究共纳入 158 例患者，147 例患者可进行生存分析。中位随访 36.1 个月后，A 组和 B 组的中位 RFS 分别为 17.9 个月和 22.5 个月（P=0.72）。分层分析显示，IIIb-IIIc 期患者的 RFS 曲线在 A 组和 B 组之间存在统计学差异（P=0.02）。淋巴结转移较多（n⩾3）的患者 RFS 更短（P=0.004），A 组为 3.3 个月，B 组为 11.9 个月。两组均观察到 1/2 级不良事件。然而，B 组患者更易发生可逆性 3/4 级肝毒性（P=0.03）。
诱导剂量 15×10(6)U/m(2)和维持剂量 9×10(6)U 是可以耐受的，这可能是中国高危 AM 人群辅助 IFN-α-2b 治疗的可选剂量强度。4 周方案和 1 年方案的 RFS 无统计学差异，而 1 年方案可能对 IIIb-IIIc 期 AM 或淋巴结转移≥3 个的患者具有临床获益。
