Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial

被引:127
作者
Marco, Michael R. [1 ]
Zhou, Lihong [1 ]
Patil, Sujata [2 ]
Marcet, Jorge E. [3 ]
Varma, Madhulika G. [4 ]
Oommen, Samuel [5 ]
Cataldo, Peter A. [6 ]
Hunt, Steven R. [7 ]
Kumar, Anjali [8 ]
Herzig, Daniel O. [9 ]
Fichera, Alessandro [10 ]
Polite, Blase N. [11 ]
Hyman, Neil H. [12 ]
Ternent, Charles A. [13 ]
Stamos, Michael J. [14 ]
Pigazzi, Alessio [14 ]
Dietz, David [15 ]
Yakunina, Yuliya [1 ]
Pelossof, Raphael [1 ]
Garcia-Aguilar, Julio [1 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10021 USA
[3] Univ S Florida, Dept Surg, Tampa, FL USA
[4] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA
[5] John Muir Hlth, Dept Surg, Concord, CA USA
[6] Univ Vermont, Dept Surg, Burlington, VT 05405 USA
[7] Washington Univ, Dept Surg, St Louis, MO USA
[8] Washington State Univ, Dept Surg, Spokane, WA USA
[9] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA
[10] Univ N Carolina, Dept Surg, Chapel Hill, NC 27515 USA
[11] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA
[12] Univ Chicago, Dept Surg, 5841 S Maryland Ave, Chicago, IL 60637 USA
[13] Univ Nebraska, Coll Med, Creighton Univ, Dept Surg,Med Ctr, Omaha, NE 68198 USA
[14] Univ Calif Irvine, Dept Surg, Irvine, CA 92717 USA
[15] Univ Hosp Cleveland Med Ctr, Dept Surg, Cleveland, OH USA
关键词
Adjuvant chemotherapy; Chemotherapy; Chemotherapy compliance; Consolidation chemotherapy; Disease-free survival; FOLFOX; Interval; Neoadjuvant chemotherapy; Neoadjuvant chemoradiation; Overall survival; Pathological response; Preoperative chemoradiation; Preoperative chemotherapy; Rectal cancer; Surgery; Survival; Time; Timing; Total mesorectal excision; Total neoadjuvant therapy; ypTNM stage; DISEASE-FREE SURVIVAL; PREOPERATIVE CHEMORADIOTHERAPY; POSTOPERATIVE CHEMORADIOTHERAPY; ADJUVANT CHEMOTHERAPY; FOLFOX CHEMOTHERAPY; RADIATION-THERAPY; CHEMORADIATION; SURGERY; OXALIPLATIN; EXCISION;
D O I
10.1097/DCR.0000000000001207
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response. OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Four sequential study groups with stage II or III rectal cancer were included. INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received 1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03). LIMITATIONS: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients. CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.
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收藏
页码:1146 / 1155
页数:10
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