A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX
A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX
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DOI：
10.1093/ajcn/nqaa227
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发表时间：
2020-12-01
影响因子：
7.1
通讯作者：
Senesse, Pierre
中科院分区：
文献类型：
--
作者：
Boisselier, Pierre;Kaminsky, Marie-Christine;Senesse, Pierre
背景资料：在先前的第二阶段研究中发现，免疫营养素补充剂，以减少严重的急性毒性头颈部鳞状细胞癌（HNSCC）患者治疗伴随顺铂和radiotherapy.Objectives：本研究的主要目的是评估疗效相同的免疫营养素补充剂对严重的粘膜炎。次要目标包括耐受性，遵守口服补充剂，化疗中断和延迟，生活质量，和无进展生存期（PFS）和总生存期（OS）在1.2年和3年。方法：2009年11月至2013年6月，180 HNSCC患者手术后辅助化疗治疗的目的，包括在我们的双盲III期多中心试验。他们被分配接受口服补充剂（3袋/天）的配方富含L-精氨酸和ω-3（n-3）脂肪和核糖核酸（实验组），或等热量等氮对照（对照组），前5天的顺铂的3个周期。进行意向治疗（ITT）和符合方案（PP）分析，沿着对依从性≥ 75%的患者进行亚组分析，以比较急性粘膜炎的发生率（放射治疗肿瘤组和WHO量表）和36个月生存率。在终止化放疗（CRT）后1个月，治疗组之间3-4级粘膜炎的发生率无差异，在ITT、PP（172例患者）和亚组（>= 75%依从性，n = 112）分析中。在ITT和PP分析中，免疫调节补充剂没有显著改善CRT后3年的生存率。然而，在依从性>= 75%的患者中，免疫调节配方奶粉组3年OS（81%; 95% CI：67%，89%）与对照组（61%; 95% CI：46%）相比显著改善。73%; P = 0.034），以及PPS（73%，95%CI：58%，83% vs. 50%，95%CI：36%，63%，P = 0.012）。结论：尽管这种免疫调节配方未能减少CRT期间严重的粘膜炎，但研究结果表明，依从性HNSCC患者的长期生存率得到改善。
Background: In a previous phase II study an immunonutrient supplement was found to reduce severe acute toxicities for head and neck squamous cell cancer (HNSCC) patients treated with concomitant cisplatin and radiotherapy.Objectives: The primary objective of the present study was to evaluate efficacy of the same immunonutrient supplement on severe mucositis. Secondary objectives included tolerance, compliance to oral supplementation, chemotherapy interruptions and delays, quality of life, and progression-free survival (PFS) and overall survival (OS) at 1.2, and 3 y.Methods: Between November 2009 and June 2013,180 HNSCC patients eligible for adjuvant chemotherapy after surgery with curative intent were included in our double-blind phase III multicenter trial. They were assigned to receive oral supplementation (3 sachets/d) of either a formula enriched with L-arginine and omega-3 (n-3) fatty and ribonucleic acids (experimental arm), or an isocaloric isonitrogenous control (control arm), for 5 d before each of 3 cycles of cisplatin. Intention-to-treat (ITT) and per-protocol (PP) analyses were undertaken, along with subgroup analyses of >= 75% compliant patients, to compare the incidence of acute mucositis (Radiation Therapy Oncology Group and WHO scales) and 36-mo survival.Results: At 1 mo after terminating chemoradiotherapy (CRT), no differences were observed in the incidence of grade 3-4 mucositis between treatment groups, in the ITT, PP (172 patients), and subgroup (>= 75% compliance, n = 112) analyses. The immunomodulating supplement did not significantly improve survival in the ITT and PP analyses at 3 y after CRT. Among >= 75% compliant patients, however, OS at 3 y was significantly improved in the immunomodulating formula group (81%; 95% Cl: 67%, 89%) compared with controls (61%; 95% CI: 46%. 73%; P = 0.034), as well as PPS (73%; 95% CI: 58%, 83% compared with 50%; 95% CI: 36%, 63%; P = 0.012).Conclusions: Although this immunomodulating formula failed to reduce severe mucositis during CRT, the findings suggest that the long-term survival of compliant HNSCC patients was improved.