Citation: Lancet Oncology. 16(8):957-66, 2015 Aug..Journal: The Lancet. Oncology.ISSN: 1470-2045.Full author list: Garcia-Aguilar J; Chow OS; Smith DD; Marcet JE; Cataldo PA; Varma MG; Kumar AS; Oommen S; Coutsoftides T; Hunt SR; Stamos MJ; Ternent CA; Herzig DO; Fichera A; Polite BN; Dietz DW; Patil S; Avila K; Timing of Rectal Cancer Response to Chemoradiation Consortium.UI/PMID: 26187751.Subject(s): Adenocarcinoma/pa [Pathology] | *Adenocarcinoma/th [Therapy] | Adult | Aged | Aged, 80 and over | Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects] | *Antineoplastic Combined Chemotherapy Protocols/tu [Therapeutic Use] | Canada | Chemoradiotherapy, Adjuvant/ae [Adverse Effects] | *Chemoradiotherapy, Adjuvant | Disease Progression | Drug Administration Schedule | Female | Fluorouracil/ad [Administration & Dosage] | Humans | Infusions, Intravenous | Intention to Treat Analysis | Leucovorin/ad [Administration & Dosage] | Logistic Models | Male | Middle Aged | Multivariate Analysis | Neoadjuvant Therapy/ae [Adverse Effects] | *Neoadjuvant Therapy | Neoplasm Staging | Odds Ratio | Organoplatinum Compounds/ad [Administration & Dosage] | Rectal Neoplasms/pa [Pathology] | *Rectal Neoplasms/th [Therapy] | Remission Induction | Time Factors | Treatment Outcome | United StatesInstitution(s): MedStar Washington Hospital CenterDepartment(s): Surgery/Colorectal SurgeryActivity type: Journal Article.Medline article type(s): Clinical Trial, Phase II | Journal Article | Multicenter Study | Research Support, N.I.H., ExtramuralOnline resources: Click here to access onlineDigital Object Identifier: http://dx.doi.org/10.1016/S1470-2045(15)00004-2 (Click here)Abbreviated citation: Lancet Oncol. 16(8):957-66, 2015 Aug.Local Holdings: Available online from MWHC library: 2001 - present.Abstract: BACKGROUND: Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response.Abstract: METHODS: We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 450 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 54 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816.Abstract: FINDINGS: Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=00036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 349, 95% CI 139-875; p=0011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients).Abstract: INTERPRETATION: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials.Abstract: FUNDING: National Institutes of Health National Cancer Institute.Copyright � 2015 Elsevier Ltd. All rights reserved.