Open-Label, Multicenter, Randomized Phase III Trial of Adjuvant Chemoradiation Plus Interferon Alfa-2b Versus Fluorouracil and Folinic Acid for Patients With Resected Pancreatic Adenocarcinoma
Open-Label, Multicenter, Randomized Phase III Trial of Adjuvant Chemoradiation Plus Interferon Alfa-2b Versus Fluorouracil and Folinic Acid for Patients With Resected Pancreatic Adenocarcinoma
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DOI：
10.1200/jco.2011.38.2960
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发表时间：
2012-11-20
影响因子：
45.3
通讯作者：
Buechler, Markus W.
中科院分区：
文献类型：
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作者：
Schmidt, Jan;Abel, Ulrich;Buechler, Markus W.
目的：胰腺癌患者辅助化疗可提高生存率，但其益处有限。在II期试验中，辅助放化疗后长达44个月的长期生存时间激发了本研究。患者和方法在2004年至2007年期间，132例R 0/R1切除患者接受氟尿嘧啶（FU）、顺铂和干扰素α-2b（IFN α-2 B）加放疗，随后进行2个周期的FU（A组，n = 64）或6个周期的FU单药治疗（B组，n = 68）。110例患者（A组，n = 53; B组，n = 57）接受了至少一剂研究药物，这些患者构成符合方案（PP）人群。纵向分析生物标志物的预测value.ResultsMedian生存为所有随机分配的患者为26.5个月（95%CI，21.6至39.5个月），在A组和28.5个月（95%CI，20.4至38.6个月），在臂B。风险比为1.04（A组vs B组：95% CI，0.66 - 1.53; P = 0.99）。A组PP人群的中位生存期为32.1个月（95% CI，22.8 - 42.2个月），B组为28.5个月（95% CI，19.5 - 38.6个月）（P = 0.49）。A组85%的患者和B组16%的患者发生3级或4级毒性。A组的生活质量暂时受到负面影响。结论与FU单药治疗相比，FU、顺铂和IFN α-2b联合放疗方案并未改善生存率。鉴于严重的不良反应，目前不推荐这种治疗。然而，据我们所知，两组的结果都代表了胰腺癌切除患者在随机对照试验中的最佳生存率。未来的研究将证明对IFN α-2b攻击的免疫应答是否具有预测价值。
PurposeAdjuvant chemotherapy prolongs survival in patients with pancreatic cancer, but its benefit is limited. Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study.Patients and MethodsBetween 2004 and 2007, 132 R0/R1 resected patients received either fluorouracil (FU), cisplatin, and interferon alfa-2b (IFN alpha-2b) plus radiotherapy followed by two cycles of FU (arm A, n = 64) or six cycles of FU monotherapy (arm B, n = 68). One hundred ten patients (arm A, n = 53; arm B, n = 57) received at least one dose of the study medication, and these patients composed the per-protocol (PP) population. Biomarkers were analyzed longitudinally for their predictive value.ResultsMedian survival for all randomly assigned patients was 26.5 months (95% CI, 21.6 to 39.5 months) in arm A and 28.5 months (95% CI, 20.4 to 38.6 months) in arm B. The hazard ratio was 1.04 (arm A v arm B: 95% CI, 0.66 to 1.53; P = .99). Median survival for the PP population was 32.1 months (95% CI, 22.8 to 42.2 months) in arm A and 28.5 months (95% CI, 19.5 to 38.6 months) in arm B (P = .49). Eighty-five percent of patients in arm A and 16% of patients in arm B experienced grade 3 or 4 toxicity. The quality of life was temporarily negatively affected in arm A.ConclusionThe FU, cisplatin, and IFN alpha-2b plus radiotherapy regimen did not improve the survival compared with FU monotherapy. Given the substantial adverse effects, this treatment can currently not be recommended. Nevertheless, the outcome in both arms represents the best survival, to our knowledge, ever reported for patients with resected pancreatic cancer in randomized controlled trials. Future studies will demonstrate whether immune response to IFN alpha-2b challenge has a predictive value.