Sarah Cannon Research Institute, Nashville, TN 37203, USA.
Clin Colorectal Cancer. 2012 Mar;11(1):45-52. doi: 10.1016/j.clcc.2011.04.002. Epub 2011 Aug 15.
We wanted to evaluate the efficacy, defined as 2-year disease-free survival (DFS), and safety of bevacizumab/chemoradiation in preoperative and adjuvant settings for patients with stage II/III rectal cancer.
Eligible patients had stage II/III rectal adenocarcinoma, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and adequate organ function, and received preoperative (cohort A) or adjuvant (cohort B) treatment at physician discretion. Patients received 5-fluorouracil (5-FU) as an intravenous infusion (IVCI) 225 mg/m(2)/d on days 1-42, bevacizumab 5 mg/kg intravenously (I.V.) on days 1 and 15 (cohort A), or every 2 weeks (cohort B), with radiation therapy to 50.4 Gy. After surgery (cohort A) or chemoradiation (cohort B), FOLFOX6 (5-fluorouracil, leucovorin, oxaliplatin) and bevacizumab were administered for 4 months and then bevacizumab was given alone for up to 1 year.
Sixty-six patients (cohort A = 35; cohort B = 31) were enrolled from August 2006-April 2009: median age was 57 years; male patients, 62%; ECOG PS 0, 75%; stage II/III, 31%/69%. In cohort A, the complete pathologic response (pCR) rate was 29% (11% microscopic residual disease, 49% gross disease). Four patients did not undergo surgery (toxicity, 2 patients; progressive disease, 1 patient; patient decision, 1 patient). One- and 2-year DFS for cohorts A/B were 85%/not reached and 97%/89%, respectively (median survival not reached for either cohort). Frequent grade 3/4 toxicity included diarrhea (A cohort, 14%; B cohort, 29%), neutropenia (A cohort, 14%, B cohort, 23%), mucositis (A cohort, 23%, B cohort, 0%), and fatigue (A cohort, 6%, B cohort, 10%). Other serious toxicity included bowel perforation and pelvic infection (cohort A, 1 patient each), bowel perforation (2 patients), anal wound dehiscence (1 patient), perianal infection (2 patients), and rectovaginal fistula (1 patient) (cohort B), without treatment-related death in either cohort.
Bevacizumab can be added to standard preoperative and adjuvant chemoradiation in most patients with expected and manageable toxicity and may increase treatment efficacy.
我们旨在评估贝伐单抗联合放化疗在术前和辅助治疗局部晚期 II/III 期直肠癌患者中的疗效（定义为 2 年无疾病生存率[DFS]）和安全性。
符合条件的患者为 II/III 期直肠腺癌，东部肿瘤协作组体能状态（ECOG PS）0-1 分，且器官功能良好，可接受术前（队列 A）或辅助（队列 B）治疗。患者接受 5-氟尿嘧啶（5-FU）静脉滴注（IVCI）225 mg/m²/天，连续 42 天；贝伐单抗 5 mg/kg 静脉注射（I.V.），第 1 天和第 15 天（队列 A），或每 2 周（队列 B）一次，同时行 50.4 Gy 放疗。手术后（队列 A）或放化疗后（队列 B），给予 FOLFOX6（5-氟尿嘧啶、亚叶酸钙、奥沙利铂）联合贝伐单抗治疗 4 个月，然后单独使用贝伐单抗治疗 1 年。
2006 年 8 月至 2009 年 4 月共纳入 66 例患者（队列 A = 35 例；队列 B = 31 例）：中位年龄 57 岁；男性患者占 62%；ECOG PS 0 分，占 75%；II/III 期患者，分别占 31%和 69%。在队列 A 中，完全病理缓解（pCR）率为 29%（11%为显微镜下残留疾病，49%为大体疾病）。4 例患者未行手术（毒性，2 例；疾病进展，1 例；患者决定，1 例）。队列 A/B 的 1 年和 2 年 DFS 率分别为 85%/未达到和 97%/89%（两组的中位生存时间均未达到）。常见的 3/4 级毒性包括腹泻（队列 A，14%；队列 B，29%）、中性粒细胞减少（队列 A，14%，队列 B，23%）、黏膜炎（队列 A，23%，队列 B，0%）和疲劳（队列 A，6%，队列 B，10%）。其他严重毒性包括肠穿孔和骨盆感染（队列 A，各 1 例）、肠穿孔（2 例）、肛门伤口裂开（1 例）、肛周感染（2 例）和直肠阴道瘘（1 例）（队列 B），两组均无治疗相关死亡。
贝伐单抗可联合标准术前和辅助放化疗，大多数患者的毒性反应可预期且可管理，可能提高治疗效果。
