TY - JOUR
T1 - Consolidation mFOLFOX6 chemotherapy after chemoradiotherapy improves survival in patients with locally advanced rectal cancer
T2 - Final results of a multicenter phase II trial
AU - Marco, Michael R.
AU - Zhou, Lihong
AU - Patil, Sujata
AU - Marcet, Jorge E.
AU - Varma, Madhulika G.
AU - Oommen, Samuel
AU - Cataldo, Peter A.
AU - Hunt, Steven R.
AU - Kumar, Anjali
AU - Herzig, Daniel O.
AU - Fichera, Alessandro
AU - Polite, Blase N.
AU - Hyman, Neil H.
AU - Ternent, Charles A.
AU - Stamos, Michael J.
AU - Pigazzi, Alessio
AU - Dietz, David
AU - Yakunina, Yuliya
AU - Pelossof, Raphael
AU - Garcia-Aguilar, Julio
N1 - Publisher Copyright:
© The ASCRS 2018.
PY - 2018
Y1 - 2018
N2 - 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 followup. 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.
AB - 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 followup. 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.
KW - Adjuvant chemotherapy
KW - Chemotherapy
KW - Chemotherapy compliance
KW - Consolidation chemotherapy
KW - Disease-free survival
KW - FOLFOX
KW - Interval
KW - Neoadjuvant chemoradiation
KW - Neoadjuvant chemotherapy
KW - Overall survival
KW - Pathological response
KW - Preoperative chemoradiation
KW - Preoperative chemotherapy
KW - Rectal cancer
KW - Surgery
KW - Survival
KW - Time
KW - Timing
KW - Total mesorectal excision
KW - Total neoadjuvant therapy
KW - YpTNM stage
UR - http://www.scopus.com/inward/record.url?scp=85053318425&partnerID=8YFLogxK
U2 - 10.1097/DCR.0000000000001207
DO - 10.1097/DCR.0000000000001207
M3 - Article
C2 - 30192323
AN - SCOPUS:85053318425
SN - 0012-3706
VL - 61
SP - 1146
EP - 1155
JO - Diseases of the Colon and Rectum
JF - Diseases of the Colon and Rectum
IS - 10
ER -