Chiarion-Sileni Vanna, Del Bianco Paola, Romanini Antonella, Guida Michele, Paccagnella Adriano, Dalla Palma Maurizio, Naglieri Emanuele, Ridolfi Ruggero, Silvestri Barbara, Michiara Maria, De Salvo Gian Luca
Department of Medical Oncology, University Hospital, Padua, Italy.
BMC Cancer. 2006 Feb 27;6:44. doi: 10.1186/1471-2407-6-44.
High-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described.
Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m2/d intravenously (IV) 5 days/week x 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IFNalfa-2b 20 MU/m2/d IV 5 days/week x 4 weeks followed by 10 MU/m2 subcutaneously (SC) three times per week x 48 weeks (High Dose Interferon, HDI, arm). Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle.
The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psychiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9%) (p = 0.0074), yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m2/week) was statistically higher than that delivered in the HDI arm (30.7 MU/m2/week) (p = 0.003).
Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited.
根据东部肿瘤协作组（ECOG）1684方案，高剂量干扰素α-2b（IFNα-2b）是美国食品药品监督管理局（FDA）和欧洲药品管理局（EMEA）批准的唯一用于III期黑色素瘤患者的辅助治疗药物。然而，其风险/获益情况受到质疑，限制了其在全球范围内的使用。在九十年代后期，意大利黑色素瘤协作组启动了一项自发随机临床试验（RCT），以验证一种比ECOG 1684方案更强化但疗程更短的方案是否能在不增加毒性的情况下提高生存率。本文描述了完成治疗的前169例患者的安全性分析。
III期黑色素瘤患者被随机分为两组，一组接受IFNα-2b 20 MU/m²/d静脉注射（IV），每周5天，共4周，在第9至12周、17至20周、25至28周重复三次（剂量密集/剂量强化，DD/DI组）；另一组接受IFNα-2b 20 MU/m²/d静脉注射，每周5天，共4周，随后皮下注射（SC）10 MU/m²，每周三次，共48周（高剂量干扰素，HDI组）。根据世界卫生组织（WHO）标准记录毒性并分级，以每个周期中出现的最严重级别为准。
两组中最常见的毒性反应为流感样症状、胃肠道症状、白细胞减少、肝脏及神经精神疾病；关于严重毒性反应，仅白细胞减少在DD/DI组中的发生率在统计学上高于HDI组（24%对9%）（p = 0.0074），然而，这并未导致感染风险增加。DD/DI组和HDI组分别有13%和17%的患者因毒性反应而停药。DD/DI组实际递送的中位剂量强度（36.4 MU/m²/周）在统计学上高于HDI组（30.7 MU/m²/周）（p = 0.003）。
四个周期的静脉高剂量IFNα-2b可以安全给药，且中位剂量强度有所增加。热切期待该试验的疗效结果。
