Author | Year | Phase | Disease stage | n | RT dose | Conc. CHT | Adj. CHT | pCR rate (%) | downst | 3y-DFS | tox gr.3+ | postop. c |
|---|
Mehta [38] | 2003 | II | T3 or T2N+ | 32 | 50.4 | 5-FU ci + Iri | n.s | 38 | 71%1 | n.r | n.r | n.r |
Hofheinz [39] | 2005 | I | T3/4 | 19 | 50.4 | Cap (esc) + Iri | n.s | 21 | 75%1 | n.r | DLT 21% | 11%20 |
Klautke [40] | 2005 | II | T3/4 or T2N+ 2 | 37 | 50.4 | 5-FU ci + Iri | 5-FU +/− FA | 22 | n.r | 73%17 | n.r | n.r |
Klautke [41] | 2006 | I/II | T3/4 or T2N+ | 28 | 55.8 | Cap (esc) + Iri | 5-FU + / − FA | 16 | n.r | n.r | 20%19 | 4% |
Navarro [42] | 2006 | II | T3/4 | 74 | 45 | 5-FU ci + Iri | dis | 14 | 49% 1 | n.r | n.r | n.r |
Willeke [43] | 2007 | II | T3/4 or N+ | 36 | 50 | Cap + Iri | dis | 15 | n.r | n.r | DLT 19% | n.r |
Glynne-Jones [44] | 2007 | I/II | T3/43 | 57 | 45 | 5-FU/LV + Iri (esc) | n.s | 21 | 41%1 | n.r | DLT 12% | n.r |
Shin [45] | 2010 | II | T3/4 or N+ | 43 | 50.4 | S-1 + Iri | n.s | 21 | n.r | 72% | 23% | n.r |
Gollins [46] | 2011 | I/II | T3/44 | 110 | 45 | Cap + Iri | dis | 22 | n.r | 64% | n.r | n.r |
Sato [47] | 2011 | II | T3/4 or N+ | 67 | 45 | S-1 + Iri | S-1 + Iri12 | 35 | n.r | n.r | 15% | 3%20 |
Hong [48] | 2011 | II | T3/4 | 48 | 50.4 | Cap + Iri | Cap | 25 | n.r | 75%18 | no gr. 4 | 5%20 |
Wong [49, 50] | 2012 | II, rand | T3/4 | 1115 | 50.4 | Cap + Iri | FOLFOX | 12 | n.r | 68%17 | 27% | 19% |
RTOG 0247 | | | | | 50.4 | Cap + Ox | FOLFOX | 23 | n.r | 62%17 | 27% | 20% |
Mohiuddin [51, 52] | 2013 | II, rand | T3/4 | 106 | 55.2–6013 | 5-FU | rec.6 | 28 | n.r | n.r | 42% | n.r |
RTOG 0012 | | | | | 50.4–54 | 5-FU + Iri | rec.6 | 28 | n.r | n.r | 51% | n.r |
Zhu [53] | 2018 | I | T3-47 | 26 | 50 | Cap + Iri (esc)14 | n.s | 25 | n.r | n.r | DLT 20% | 4%20 |
Guan [54] | 2019 | II | T3/48 | 52 | 50 | Cap + Iri14 | Cap +/− Ox21 | 28 | n.r | n.r | 38% | n.r |
Zhang [55]9 | 2019 | III | T3/47 | 360 | 50 | Cap15 | n.r | 18 | n.r | n.r | Tox sig | n. sig |
CinClare | | | | | 50 | Cap + Iri10,14 | n.r | 34 | n.r | n.r | inc. w. Iri | |
Wang [56] | 2020 | Pooled | T3/4 or N+ | 371 | 50 | Cap + Iri (var)14 | XELOX16 | 2311 | n.r | n.r | n.r | n.r |
- n = number of patients, RT dose: radiation dose in Gy, conc. CHT: concurrent chemotherapy, adj. CHT: adjuvant chemotherapy (after surgery), pCR rate: percentage of patients with pathological complete remission, downst.: percentage of patients with major downstaging defined according to study protocol (only listed if combined T and N downstaging was reported), 3y-DFS: 3-year disease-free survival, tox gr.3+: acute toxicity during combined chemoradiation grade 3 or higher (only listed if an overall percentage was reported), postop. c.: postoperative complications grade 3 or higher (only listed if an overall percentage was reported), 5-FU: 5-Fluorouracil, ci: contineous infusion, Iri: Irinotecan, mg: milligram, n.s.: not specified, n.r.: not reported, Cap: capecitabine, esc: doses were escalated during study, FA: folinic acid, y: years, dis.: at discretion of the treating physician, LV: leucovorin, S-1: oral fluoropyrimidin prodrug, DLT: dose limiting toxicity as specified in the protocol, Ox: Oxaliplatin, rand.: randomized, FOLFOX: combination regimen including 5-Fluorouracil, Leucovorin and Oxaliplatin, RTOG: radiation therapy oncology group, XELIRI: combination regimen including capecitabine and Irinotecan, XELOX: combination regimen including capecitabine and Oxaliplatin, sig. significantly, inc.: increased, w.: with, gr.: grade, mFOLFOX6: FOLFOX: combination regimen including 5-Fluorouracil, Leucovorin and Oxaliplatin as specified in the protocol, 1: downstaging defined as reduction from clinical to pathological stage, 2: uncertain R0 resection or sphincter preservation, 3: fixed tumors or threated mesorectal fascia, 4: tumor threatening (≤ 2 mm) or exceeding mesorectal fascia, 5: only patients after study amendment evaluated, 6: adjuvant chemotherapy was recommended for all patients with residual disease, in patients without residual disease Chemotherapy was at the discretion of the treating physician, 7: limited to patients with UGT1A1*1*1 or *1*28 phenotype, 8: limited to patients with UGTA1*1*1 phenotype, 9: published as abstract only, 10: Irinotecan dose was based on UGTA1 phenotype, var: variable doses, 11: pCR rate significantly increaesd with > 4 cycles of Irinotecan, 12: in patients with ypN+, 13: hyperfractionated RT with 1.2 Gy 2 times per day, 14: one cycle consolidation chemotherapy (prior to surgery) with XELIRI, 15: one cycle of consolidation chemotherapy (prior to surgery) with XELOX, 16: mFOLFOX6 also allowed, 17: 4-year rates, 18: 5-year rates, 19: in phase II part, 20: re-operation rate, n. sig.: no signficant difference between arms, 21: 5-FU instead of Cap allowed, bold style: indicates significant difference
