Preoperative Chemotherapy in Patients With Intermediate‐Risk Rectal Adenocarcinoma Selected by High‐Resolution Magnetic Resonance Imaging: The GEMCAD 0801 Phase II Multicenter Trial. (10th September 2014)

• Record Type: Journal Article
• Authors: Fernandez‐Martos, Carlos; Brown, Gina; Estevan, Rafael; Salud, Antonieta; Montagut, Clara; Maurel, Joan; Safont, Maria Jose; Aparicio, Jorge; Feliu, Jaime; Vera, Ruth; Alonso, Vicente; Gallego, Javier; Martin, Marta; Pera, Miguel; Sierra, Enrique; Serra, Javier; Delgado, Salvadora; Roig, Jose V.; Santos, Jesus; Pericay, Carles
• Is Part Of: Oncologist. Volume 19:Number 10(2014)
• Page Start: 1042
• Page End: 1043
• Publication Date: 2014-09-10
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2014-0233
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : Background: The need for preoperative chemoradiation or short‐course radiation in all T3 rectal tumors is a controversial issue. A multicenter phase II trial was undertaken to evaluate the efficacy and safety of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab in patients with intermediate‐risk rectal adenocarcinoma. Methods: We recruited 46 patients with T3 rectal adenocarcinoma selected by magnetic resonance imaging (MRI) who were candidates for (R0) resection located in the middle third with clear mesorectal fascia and who were selected by pelvic MRI. Patients received four cycles of neoadjuvant capecitabine and oxaliplatin combined with bevacizumab (final cycle without bevacizumab) before total mesorectal excision (TME). In case of progression, preoperative chemoradiation was planned. The primary endpoint was overall response rate (ORR). Results: On an intent‐to‐treat analysis, the ORR was 78% ( n = 36; 95% confidence interval [CI]: 63%–89%) and no progression was detected. Pathologic complete response was observed in nine patients (20%; 95% CI: 9–33), and T downstaging was observed in 48%. Forty‐four patients proceeded to TME, and all had R0 resection. During preoperative therapy, two deaths occurred as a result of pulmonary embolism and diarrhea, respectively, and one patient died after surgery as a result of peritonitis secondary to an anastomotic leak (AL). A 13% rate of AL was higher than expected. The 24‐month disease‐free survival rate was 75% (95% CI: 60%–85%), and the 2‐year local relapse rate was 2% (95% CI: 0%–11%). Conclusion: In this selected population, initial chemotherapy results in promising activity, but the observed toxicity does not support further investigation of this specific regimen. Nevertheless, these early results warrant further testing of this strategy in an enriched population and in randomized trials. Abstract : 摘要 背景 . 目前，关于是否所有T3期直肠癌患者都需要术前放化疗或短程放疗尚存争议。我们开展了一项多中心II期临床试验，旨在评价卡培他滨和奥沙利铂联合贝伐珠单抗新辅助治疗在中危直肠腺癌患者中的有效性和安全性。 方法 . 我们招募了46例T3期直肠腺癌患者。这些患者为经磁共振成像（MRI）选择的R0切除候选对象，肿瘤位于直肠中段且直肠系膜筋膜边界清晰。同时还使用盆腔MRI对患者进行了筛选。给予患者4个周期的卡培他滨和奥沙利铂联合贝伐珠单抗（最后一个周期不给予贝伐珠单抗）新辅助治疗，之后行全直肠系膜切除术（TME）。如发生疾病进展，则按计划给予术前放化疗。主要终点为总缓解率（ORR）。 结果 . 意向性治疗分析中ORR为78%[n = 36，95%可信区间（CI）：63% ∼ 89%]，未发现疾病进展。观察到9例患者出现病理学完全缓解（20%，95%CI：9% ∼ 33%），48%的患者发生T分期降期。44例患者继而接受TME，均为R0切除。在术前治疗期间，2例患者分别因肺栓塞和腹泻死亡，1例患者在手术后因吻合口瘘（AL）继发腹膜炎死亡。AL发生率为13%，高于我们的预期。24个月无病生存率为75%（95%CI：60% ∼ 85%），2年局部复发率为2%（95%CI：0% ∼ 11%）。 结论 . 本研究结果显示，起始化疗的活性在这一经选择的患者人群中颇有希望，但观察到的毒性事件不支持对这一特定方案进一步研究。尽管如此，我们获得的这些早期结果提示有必要在更丰富的人群和随机对照临床试验中对这一方案开展进一步检验。 The Oncologist 2014;19: 1042‐1043