Retrospective Study
Copyright ©The Author(s) 2021.
World J Gastrointest Oncol. Apr 15, 2021; 13(4): 252-264
Published online Apr 15, 2021. doi: 10.4251/wjgo.v13.i4.252
Table 5 Summaries of studies on neoadjuvant chemotherapy followed by chemoradiotherapy
Study        
Design
n
Eligibility
NAC regimen
CRT regimen
AC regimen
Response
Compliance
Recurrence
Survival
Chau et al[3]Prospective single-arm36cT3N0-2; cT4N0-2MMC (× 2); PVI 5-FURT 54Gy/30Fx’s; PVI 5-FUMMC; PVI 5-FU27.8%1 after NAC; 80.6%1 after CRT NAC 100%; CRT 100%LR 2 pts; DM 9 pts1Y-OS 93.5%; 2Y-OS 70.3%
EXPERT[4,5] Phase II single-arm105MR defined disease: MRF involved or threatened, cT3 tumor at or below the levators, cT4, cN2, extramural extension ≥ 5 mmCAPOX (× 4)RT 54Gy/30Fx’s; capecitabinecapecitabine74%1 after NAC; 89%1 after CRT NAC 89%; CRT 91%LR 6 pts; DM 21 pts5Y-OS 75.0%
GCR-3[6,7] Phase II; RCT54MR defined disease: Distal edge within 12 cm from AV, lower third cT3, resectable cT4, cT3-4N+, MRF involved or threatenedCAPOX (× 4)RT 54Gy/27Fx’s; CAPOX-Downstaging 43.0%; pCR 14.0%NAC 94.0%; CRT 85.0%LR 5%; DM 23%5Y-OS 75.0%
49-RT 54Gy/27Fx’s; CAPOXCAPOX (× 4)Downstaging 58.0%; pCR 13.0%CRT 80.0%; AC 57.0%LR 2%; DM 21%5Y-OS 78.0%
COPERNICUS[8]Phase II single-arm60Inferior margin ≥ 4 cm from AV, superior margin < S1/2 interspace, tumor > 1 mm from MRF, cT3d, cT4, mrT3a-b with either EMV invasion or mesorectal lymph nodes Oxaliplatin/5-FU (× 4)RT 25Gy/5Fx’sOxaliplatin 5-FU (× 8)T down staging: 73.0%1 after NAC; 74.0% after surgery NAC 75.0%; AC 37.0%LR 2 pts; DM 6 pts2Y-PFS 86.2%
CONTRE[9]Prospective single-arm39cT3-4N0, cT1-4N+mFOLFOX6 (× 8)RT 50.4Gy/28Fx’s capecitabine-pCR 33.0%NAC 92.0%LR 2 pts; DM 6 pts-
Schou et al[10]Prospective single-arm84MR defined disease: MRF involved or threatened, cT3-4 N+CAPOX (× 2)RT 54Gy/27Fx’scapecitabine-T down staging 69% after surgerypCR 23.0%NAC 88.0%LR 1%DM 25%5Y-OS 67.0%
Dueland et al[11]Prospective single-arm97cT3 with < 3 mm from MRF, cT4, N+, resectable synchronous metastasisNordic FLOX (× 2)RT 50Gy/25Fx’s; CAPOX-pCR 17.3%NAC 91.0%LR 4 pts; DM 27 pts5Y-OS 83.0%
Koeberle et al[12]Phase II single-arm60cT3-4 with N- or N+CAPOX (× 1)RT 45Gy/25Fx’s; CAPOX-pCR 23.0%Oxaliplatin 87.0%--
Maréchal et al[13]Phase II RCT29cT2-4, cN+-RT 45Gy/25Fx’s; 5-FU-pCR 28%NAC 96.0%; CRT 98.0%--
28mFOLFOX6 (× 2)RT 45Gy/25Fx’s; 5-FU-pCR 25%
EXPERT-C[14]Phase II RCT81MR defined disease: Tumor within 1mm of MRF, cT3 tumor at or below the levators, cT4, presence of EMV invasion, extramural extension5mmCAPOX (× 4) cetuximabRT 54Gy/30Fx’s; capecitabine/ cetuximabCAPOX (× 4); cetuximab64.0%1 after NAC; 84.0%1 after CRT NAC 95.0%; CRT 91.0%LR 1 pt-
83CAPOX (× 4)RT 54Gy/30Fx’s; capecitabineCAPOX (x4)54.0%1 after NAC; 76.0%1 after CRT NAC 93.0%; CRT 90.0%LR 2 pts-
AVACROSS[15]Phase II single-arm47Distal edge ≤ 1 cm from AV, cT3N+, resectable cT4, cT3 tumor in lower third, tumor in middle third with ≤ 2 mm from MRF, N+ with ≤ 2 mm from MRFCAPOX/bevacizumab (× 4)RT 50Gy/25Fx’s; capecitabine/ bevacizumabCAPOX (x4)pCR 34.0%NAC 85.0%; CRT 83.0%DM 5 pts-
Eisterer et al[16] Phase II single-arm25MR defined disease: cT3 (< 5 mm from MRF), cT4CAPOX/bevacizumab (× 3)RT 45Gy/25Fx’s capecitabine-pCR 25.0%NAC 79.2%CRT 94.7%--
PRODIGE23[31]Phase III231cT3-4 mFOLFIRINOX (× 6)RT 50Gy25Fx’s; capecitabinemFOLFOX6 or capecitabinepCR 27.8%--3Y-DFS 75.7%
230-pCR 12%--3Y-DFS 68.5%
1Tumor response evaluation by imaging.
NAC: Neoadjuvant chemotherapy; CRT: Chemoradiotherapy; RT: Radiotherapy; AC: Adjuvant chemotherapy; OS: Overall survival; PFS: Progression-free survival; LR: Local recurrence; DM: Distant metastasis; MR: Magnetic resonse; AV: Anal verge; MRF: Mesorectal fascia; EMV: Extramural venous; MMC: Mitomycin C; PVI: Protracted venous infusion; CAPOX: Capecitabine/oxaliplatin; FLOX: Oxaliplatin/5-FU; FOLFIRINOX: Oxaliplatin/5-FU/Irinotecan; pCR: Pathological complete response; RCT: Randomized controlled trial.