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

Timing of Rectal Cancer Response to Chemoradiation Consortium

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1146-1155
Number of pages10
JournalDiseases of the Colon and Rectum
Volume61
Issue number10
DOIs
StatePublished - Oct 1 2018

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Consolidation Chemotherapy
Chemoradiotherapy
Rectal Neoplasms
Survival
Disease-Free Survival
oxaliplatin
Adjuvant Chemotherapy
Fluorouracil
Outcome Assessment (Health Care)
Radiation Dosage
Drug Therapy
Leucovorin

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer : Final Results of a Multicenter Phase II Trial. / Timing of Rectal Cancer Response to Chemoradiation Consortium.

In: Diseases of the Colon and Rectum, Vol. 61, No. 10, 01.10.2018, p. 1146-1155.

Research output: Contribution to journalArticle

@article{2275383bef4948bfa2e1a10ddf8c8d3b,
title = "Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial",
abstract = "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.",
author = "{Timing of Rectal Cancer Response to Chemoradiation Consortium} and Marco, {Michael R.} and Lihong Zhou and Sujata Patil and Marcet, {Jorge E.} and Varma, {Madhulika G.} and Samuel Oommen and Cataldo, {Peter A.} and Hunt, {Steven R.} and Anjali Kumar and Daniel Herzig and Alessandro Fichera and Polite, {Blase N.} and Hyman, {Neil H.} and Ternent, {Charles A.} and Stamos, {Michael J.} and Alessio Pigazzi and David Dietz and Yuliya Yakunina and Raphael Pelossof and Julio Garcia-Aguilar",
year = "2018",
month = "10",
day = "1",
doi = "10.1097/DCR.0000000000001207",
language = "English (US)",
volume = "61",
pages = "1146--1155",
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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 - Timing of Rectal Cancer Response to Chemoradiation Consortium

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

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

PY - 2018/10/1

Y1 - 2018/10/1

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 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.

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 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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DO - 10.1097/DCR.0000000000001207

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JO - Diseases of the Colon and Rectum

JF - Diseases of the Colon and Rectum

SN - 0012-3706

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