4月2日,在线发表在Journal of Clinical Oncology杂志上的一项多中心研究表明,将西妥昔单抗添加到新辅助化疗和放疗中,可提高高风险直肠癌切除术后的总体存活率。但是,没有提高完全缓解率。
虽然结果证实了新辅助化疗在治疗高风险局部直肠癌的疗效,但是作者说到,我们目前不推荐西妥昔单抗在该类病人中的常规应用。
David Cunningham博士指出,西妥昔单抗是一种有效的放射增敏剂,之前他们曾进行的II期试验表明,对于预后差的直肠癌患者在化疗和全直肠系膜切除之前实行奥沙利铂和卡倍他滨(CAPOX)新辅助化疗的可行性。
在目前的研究中,他们调查了每周加入西妥昔单抗到CAPOX疗程中的疗效,他们的分析集中在90个具有KRAS/BRAF野生型直肠癌的病人,这类病人对抗EGFR治疗易感。
主要终点是完全缓解率,加不加西妥昔单抗没有造成统计学差异,无进展生存率在两组中也类似。
西妥昔单抗确实提高了某些次要指标,两组的放射反应率新辅助化疗后分别为71% vs 51%(p=0.038),术前放化疗后分别为93% vs 75%(p=0.028)。此外,西妥昔单抗可带来更好的总体生存率。
他们得出结论,在这些成果的基础上,有足够的数据表明西妥昔单抗有一定的生物学活性,联合其他化疗方案的进一步评估可能会产生更可喜的成果。(生物谷Bioon.com)
doi:10.1200/JCO.2011.39.6036
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Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)
Alice Dewdney, David Cunningham?, Josep Tabernero, Jaume Capdevila, Bengt Glimelius, Andres Cervantes, Diana Tait, Gina Brown, Andrew Wotherspoon, David Gonzalez de Castro, Yu Jo Chua, Rachel Wong, Yolanda Barbachano, Jacqueline Oates and Ian Chau
Purpose To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer.
Patients and Methods Patients with operable magnetic resonance imaging–defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis.
Results One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX+C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX+C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX+C arm.
Conclusion Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.