Department of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, California.
City of Hope National Medical Center, Duarte, California.
Oncologist. 2020 Dec;25(12):e1879-e1885. doi: 10.1634/theoncologist.2020-0642. Epub 2020 Aug 27.
Neoadjuvant bevacizumab with modified FOLFOX7 without radiation failed to meet the goal of pathological complete response rate; however, the low number of recurrence and disease-free survival in this population, with predominantly stage III, is encouraging and worth further exploration. The racial distribution of the patient population, as well as a wait time of more than 4 weeks after last chemotherapy, may have contributed to the findings.
Combination chemotherapy in lieu of radiation in rectal adenocarcinoma is under exploration in multiple trials. We evaluated the efficacy of neoadjuvant FOLFOX + bevacizumab in patients (pts) with clinical stage II and III disease.
Pts received six cycles of bevacizumab (5 mg/kg) and modified FOLFOX7 (oxaliplatin 85 mg/m , leucovorin 20 mg/m , and fluorouracil [5-FU] 2,400 mg/m ). Surgical resection was performed 6-8 weeks after completion of treatment and upon confirmation of nonmetastatic disease. We employed a Simon two-stage design and required three pathological complete responses (pCR) in the first 18 pts, with a prespecified pCR rate of 25% before moving to the next stage.
Seventeen pts enrolled; 65% at stage III. Median age was 57 (35-79), 65% were male, 47% were Hispanic, 35% were white, and 18% were Asian. All pts but one completed six cycles of therapy. One pCR was observed (6%), and 11 of 17 (65%) pts had pathological downstaging. One patient experienced systemic recurrence and remains on treatment. Probability of disease-free survival (DFS) at 5 years is 0.94 (SE, 0.06).
The study failed to meet the required three pCRs in the first 18 pts. The DFS in this population is encouraging and supports the hypothesis that select pts with rectal cancer may be spared from radiation.
新辅助贝伐单抗联合改良 FOLFOX7 治疗未联合放疗未能达到病理完全缓解率的目标；然而，在以 III 期为主的人群中，复发和无病生存率低是令人鼓舞的，值得进一步探索。患者人群的种族分布以及末次化疗后等待时间超过 4 周可能促成了这些发现。
在多个临床试验中，正在探索替代放疗的联合化疗治疗直肠腺癌。我们评估了新辅助 FOLFOX + 贝伐单抗在 II 期和 III 期疾病患者中的疗效。
患者接受六周期贝伐单抗（5mg/kg）和改良 FOLFOX7（奥沙利铂 85mg/m²、亚叶酸 20mg/m²和氟尿嘧啶[5-FU]2400mg/m²）治疗。治疗完成后 6-8 周并在确认无转移疾病后进行手术切除。我们采用西蒙两阶段设计，在前 18 例患者中需要 3 例病理完全缓解（pCR），在进入下一个阶段之前规定 pCR 率为 25%。
17 例患者入组；65%为 III 期。中位年龄为 57 岁（35-79 岁），65%为男性，47%为西班牙裔，35%为白人，18%为亚裔。除 1 例患者外，所有患者均完成了六周期治疗。观察到 1 例 pCR（6%），17 例患者中有 11 例（65%）病理降期。1 例患者出现全身复发并仍在接受治疗。5 年无病生存率（DFS）的概率为 0.94（SE，0.06）。
该研究在前 18 例患者中未能达到所需的 3 例 pCR。该人群的 DFS 令人鼓舞，支持了这样一种假设，即选择的直肠癌患者可能可以避免放疗。
