Phase II trial of interferon-alpha in locally recurrent or metastatic squamous cell carcinoma of the head and neck: immunological and clinical correlates.
Phase II trial of interferon-alpha in locally recurrent or metastatic squamous cell carcinoma of the head and neck: immunological and clinical correlates.
复制标题
干扰素-α 在头颈局部复发或转移性鳞状细胞癌中的 II 期试验：免疫学和临床相关性。
DOI：
10.1097/00002371-199611000-00008
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Haselow,RE
中科院分区：
文献类型：
--
作者：
Vlock,DR;Andersen,J;Kalish,LA;Johnson,JT;Kirkwood,JM;Whiteside,T;Herberman,RB;Adams,GS;Oken,MM;Haselow,RE
本研究的目的是研究重组干扰素-α2b(IFN-α2b)对复发或转移性头颈部鳞状细胞癌(SCCHN)的抗肿瘤作用、宿主毒性和免疫调节作用。71名复发或转移的SCCHN患者进入了干扰素的II期非对照随机试验，按两个剂量方案进行。符合条件的SCCHN患者随机分为两组，小剂量干扰素6×10(6)U/m2，每日3次，每4周1次；大剂量干扰素12×10(6)U/m2，每周3次。观察治疗前自然杀伤细胞(NK)活性、CD3、CD4、CD5、CD8、CD16、CD19、CD56、DR和CD4/CD8比值与存活率的关系。接受低剂量干扰素治疗的患者的毒性大多为轻度至中度。大剂量干扰素的毒性更大，出现3级和4级毒性的次数明显更多。在接受大剂量干扰素治疗的大多数患者中，需要减少剂量。在四个致命的并发症中，只有一个被认为可能与治疗有关。在接受小剂量干扰素治疗的32例可评价患者中，1例完全缓解，1例病情稳定，24例进展，6例不可评价。在接受大剂量干扰素治疗的29例可评价患者中，2例完全缓解，7例病情稳定，16例进展，4例不可评价。两组的中位生存期相似(6.2个月)。由于假设干扰素可能需要更长时间的暴露才能有效，因此对接受>；或=6周治疗的患者进行了评估。接受低剂量和高剂量干扰素治疗的患者的中位生存期分别为10个月和12个月。在进入研究的所有病例中进行评估时，无论治疗时间长短，所测试的免疫参数都不是生存的显着预测因素。在接受-lt；6或>；或=6周干扰素治疗的患者之间，基线NK活性没有差异(p=0.90)。然而，在接受>；or=6周治疗的35名患者中，高基线NK活性是一个显著的生存期预测因素(p=0.04)。复发或转移性SCCHN患者对干扰素耐受性良好。大剂量组较高的毒性发生率可通过将剂量减少50%来改善。在接受6周或更长时间治疗的患者中，基线NK活性的升高与生存期的增加有关，这表明干扰素可能起到免疫调节作用。虽然总体应答率很低，但病情稳定，这表明干扰素在这组经过大量预治疗的患者中具有抗增殖、无细胞毒性的作用。
The objective of this study was to study the antitumor, host toxicity, and immunomodulatory effects of recombinant interferon-alpha 2b (IFN) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Seventy-one patients with recurrent or metastatic SCCHN were entered into a phase II noncomparative randomized trial of IFN at two dosage schedules. Eligible patients with histologically proven SCCHN were randomized to receive low-dose IFN, 6 x 10 (6) U/m2 daily x 3 every 4 weeks or high-dose IFN, 12 x 10 (6) U/m2, 3 x/week. Pretreatment levels of natural killer (NK) activity, CD3, CD4, CD5, CD8, CD16, CD19, CD56, DR, and the CD4/CD8 ratio were evaluated for any relationship with survival. The toxicity encountered in patients receiving low-dose IFN was for the most part mild to moderate. With high-dose IFN, toxicity was greater with significantly more episodes of grade 3 and 4 toxicity encountered. Dosage reduction was required in the majority of patients receiving high-dose IFN. Of the four lethal complications, only one was thought to be possibly associated with therapy. Of the 32 evaluable patients receiving low-dose IFN, there were 1 complete response, 1 stable disease, 24 patients with progressive disease, and 6 unevaluable. Of the 29 evaluable patients taking high-dose IFN, there were 2 complete responses, 7 with stable disease, 16 with progressive disease, and 4 patients were unevaluable. Median survival in the two arms was similar (6.2 months). Because it was postulated that a more prolonged exposure to IFN might be needed for it to be effective, patients receiving> or= 6 weeks of therapy were evaluated. Median survival in that subset was 10 and 12 months for patients receiving low-and high-dose IFN, respectively. None of the immune parameters tested was a significant predictor of survival when evaluated in all cases entered into study regardless of therapy duration. No difference in baseline NK activity was noted between patients who received< 6 or> or= 6 weeks of IFN (p= 0.90). However, among the 35 patients who received> or= 6 weeks of therapy, a high baseline NK activity was a significant predictor of the duration of survival (p= 0.04). IFN was well tolerated in patients with recurrent or metastatic SCCHN. The higher incidence of toxicity encountered in the high-dose arm could be ameliorated by reducing the dose 50%. In patients receiving 6 or more weeks of therapy, elevated baseline NK activity was associated with increases in survival, suggesting that IFN may play an immunomodulatory role. Although the overall response rates were low, disease stabilization was noted, suggesting an antiproliferative, noncytotoxic role of IFN in this group of heavily pretreated patients.