Consolidation mFOLFOX6 chemotherapy after chemoradiotherapy improves survival in patients with locally advanced rectal cancer: Final results of a multicenter phase II trial Journal Article
| Authors: | Marco, M. R.; Zhou, L.; Patil, S.; Marcet, J. E.; Varma, M. G.; Oommen, S.; Cataldo, P. A.; Hunt, S. R.; Kumar, A.; Herzig, D. O.; Fichera, A.; Polite, B. N.; Hyman, N. H.; Ternent, C. A.; Stamos, M. J.; Pigazzi, A.; Dietz, D.; Yakunina, Y.; Pelossof, R.; Garcia-Aguilar, J.; for the Timing of Rectal Cancer Response to Chemoradiation Consortium |
| Article 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. |
| Keywords: | treatment outcome; aged; disease-free survival; middle aged; clinical trial; fluorouracil; disease free survival; chemotherapy, adjuvant; cancer staging; follow up; follow-up studies; antineoplastic agent; neoplasm staging; phase 2 clinical trial; antineoplastic combined chemotherapy protocols; pathology; multicenter study; folinic acid; adjuvant chemotherapy; neoplasm invasiveness; platinum complex; oxaliplatin; rectal neoplasms; rectum tumor; organoplatinum compounds; infusions, intravenous; leucovorin; chemoradiotherapy; intravenous drug administration; rectum; controlled clinical trial (topic); tumor invasion; procedures; humans; human; male; female; non-randomized controlled trials as topic |
| Journal Title: | Diseases of the Colon and Rectum |
| Volume: | 61 |
| Issue: | 10 |
| ISSN: | 0012-3706 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2018-10-01 |
| Start Page: | 1146 |
| End Page: | 1155 |
| Language: | English |
| DOI: | 10.1097/dcr.0000000000001207 |
| PUBMED: | 30192323 |
| PROVIDER: | scopus |
| PMCID: | PMC6130918 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2018 -- Source: Scopus |
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