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Copyright ©The Author(s) 2018.
World J Gastrointest Oncol. Sep 15, 2018; 10(9): 271-281
Published online Sep 15, 2018. doi: 10.4251/wjgo.v10.i9.271
Table 1 The main randomized trials in gastric cancer that evaluate the postoperative therapy
TrialYearRandomization schemeOSDFS, PFSLimits
SWOG/INT-0116[6]2001S-alone vs S + CRT3-yr: 50% vs 41% (P = 0.005)3-yr: 48% vs 31% (P < 0.001)Low rates of D2 node dissection, 2D RT technique
Update SWOG/INT-0116[7]2012S-alone vs S + CRTHR = 1.32 (95%CI: 1.10-1.60; P = 0.0046)HR = 1.51 (95%CI: 1.25-1.83; P < 0.001)Low rates of D2 node dissection, 2D RT technique
ARTIST[11] CRITICS[16]2012 2018S + CT + CRT + CT vs S + CT CT + S + CT vs CT + S + CRTNR Median OS 43 vs 37 mo (P = 0.09)3-yr: 78% vs 74% (P = 0.086)Planned events not reached, lower % of locally advanced tumors Poor postoperative patient compliance in both treatment arms
NCC, South Korea[17]2012S + CRT vs S + CTNR5-yr: 73.5% vs 54.6%, (P = 0.056)Poor accrual Sometimes 2D RT technique
Chinese Study[18]2012S + CRT vs S + CT5-yr: 48.4% vs 41.8% (P = 0.122)5-yr: 45.2% vs 35.8% (P = NS)Small series
ACTS-GC[19]2007S-alone vs S + CT3-yr: 80.1% vs 70.1% (P = 0.003)3-yr: 59.6% vs 72.2% (P < 0.001)Closed earlier due to significant survival benefit in the CT-arm
CLASSIC[20]2012S-alone vs S + CTNR3-yr: 59% vs 74% (P < 0.0001)Stopped after the interim efficacy analysis
Table 2 The main randomized trials in gastric cancer that evaluate the preoperative therapy
TrialYearRandomization schemeOSDFS, PFSLimits
MAGIC[25]2006S-alone vs CT + S + CT5-yr 23% vs 36% (P = 0.009)3-yr 26% vs 38% (P < 0.001)Low adherence to post-operative CT, inclusion of gastroesophageal junction or lower esophagus cancer
FNCLCC/ FFCD[26]2011S-alone vs CT + S + CT5-yr 24% vs 38% (P = 0.02)5-yr 19% vs 34% (P = 0.003)Inclusion of gastroesophageal junction or lower esophagus cancer, small series
MAGIC-B[28]2017CT/Beva + S + CT/ Beva vs CT + S + CT3-yr 48.1% vs 50.3% (P = 0.36)NRInclusion of gastroesophageal junction or lower esophagus cancer
POET trial[29]2009CT + S vs CT + CRT + S3-yr 27.7% vs 47.4% (P = NS)NRGastroesophageal junction tumors, closed earlier
Table 3 The main phase I/II trials in gastric cancer that evaluate the preoperative therapy
TrialYear/typeN° of patientsTreatment scheduleMedian FUSevere toxicityClinical efficacySurvivalLimits/characteristics
Matsuda[51]2014/ Phase I9SP q15 + RTNRDiarrhea (11.1) Anorexia (11.1)PR (78) SD (22)NRMTD: CDDP 25 mg/m2
Michel[37]2014/ Phase II42FOLFIRIx4→CRT38.1 moDuring FOLFIRI (26.2) During RT (19.1)CR (8.6) Median PFS: 12.3 moMedian OS: 26.4 moReduced feasibility, 73.8% of patients completed the schedule
Trip[38]2014/ Phase I/II25CBDCA-PTX + RTNRNausea (4) Anorexia (4) Esophagitis (4) Leukopenia (12) Febrile neutropenia (4) Thrombosis (4) Fatigue (4)CR (16) PR (52)Median OS: 15 mo
Wydmanski[40]2014/ Phase II135FU + RT30.1 moNausea (7.7) Vomiting (7.7) Thrombocytopenia (92.3) Leukopenia (7.7)NRMedian OS: 17.1 mo 3-yr OS: 48%Inoperable patients. High rate of severe thrombocytopenia, with 5FU 325 mg/m2 d1-5 and 29-33
Liu[52]2017/ Phase II40SOXx1→S-1 + RT → SOXx1 → surgery→SOXx426.5 moLeukopenia (10) Neutropenia (10) Thrombocytopenia (2.5)CR (7.5) PR (30) SD (40) PD (12.5) 2-yr DFS: 47%2-yr OS: 56%Treatment compliance: 87.5%
Table 4 The main phase I/II trials in gastric cancer that evaluate the postoperative therapy
TrialYear/typeN° of patientsTreatment scheduleMedian FUSevere toxicityClinical efficacySurvivalLimits/characteristics
Michel[37]2014/Phase I21FOLFIRIx4→RCT26.6 moDuring FOLFIRI (23.8) During RT (9.5)Median PFS: 22.8 moMedian OS: 32.9 moParallel study with a neoadjuvant schedule (see above). Study closed for futility (42.9% completed the schedule)
Wang[41]2014/ Phase I185FU + RT→FOLFOX4 (8) FOLFOX4→5FU+RT (7) 5FU + RT (3)45 moNausea (11.1) Vomiting (5.6) Esophagitis (5.6) Leukopenia (11.1) Neutropenia (5.6)4-yr LRC: 93.8%4-yr OS: 68.1%MTD: 5FU 800 mg/m2 twice daily
Zhai[42]2014/ Phase II30FOLFOX6x2→5FU + RT21 moNausea (33.3) Vomiting (33.3) Diarrhea (6.7) Hepatic (3.3) Cutaneous (3.3) Neutropenia (40) Sensory (23.3)3-yr DFS: 65%3-yr OS: 72.7%
Wang[43]2014/ Phase II110FOLFOXx1→FOLFOXd1, 22 + RT→FOLFOXx543 moNausea and vomiting (14.5) Diarrhea (0.9) Anorexia (11.8) Fatigue (6.4) Abdominal pain (2.7) Leuko-/neutropenia (9.1) Hemorrhage (0.9)3-yr RFS: 67.8%3-yr OS: 77.6%Stage ≤ IIIA significant factor predicting more favorable OS
Qiu[48]2015/ Phase I21SOXx1→S-1 + RT26 moNausea (19) Vomiting (19) Fatigue (4.7) Anorexia (14.2) Leukopenia (4.7)2-yr DFS: 66.7%2-yr OS: 90.4%MTD: S-1 70 mg/m2·d
Shim[49]2016/ Phase II46SPx1→S-1 + RT→SPx256.5 moNausea (17.4) Vomiting (8.7) Diarrhea (4.3) Anorexia (15.2) Fatigue (6.5) Neutropenia (28.2) Anemia (6.5) Thrombocytopenia (4.3)3-yr DFS: 65.2%3-yr OS:76.1%Treatment compliance: 73.9% Intestinal-type tumor showed better DFS and OS
Goody[46]2016/ Phase I/II555FU-CDDP + RT36.4 moHematological (36.3) Constitutional (9) Dermatologic (3.6) Gastrointestinal (18.1) Infection (5.4) Muscoloskeletal (1.8)2-yr LRR: 16.8% 2-yr RFS: 74%2-yr OS: 85%MTD: CDDP 40 mg/m2 w1,3,5,7 Treatment compliance: 85.5%
Liu[44]2017/ Phase II55mDCFx2→TXL + RT→ mDCFx261 moNausea (63) Vomiting (49) Diarrhea (12) Anorexia (34) Fatigue (31) Neutropenia (60) Thrombocytopenia (51) Thrombocytopenia (15) Anemia (13) Febrile neutropenia (10)3-yr PFS: 75% 5-yr PFS: 59%3-yr OS: 72% 5-yr OS:61%Treatment compliance 76%
Liu[45]2017/ Phase II36mDCFx2→wTXL + RT→mDCFx235.6 moNausea (63) Vomiting (48) Diarrhea (9) Anorexia (33) Stomatitis (44) Fatigue (27) Neutropenia (53) Thrombocytopenia (62) Thrombocytopenia (16) Anemia (13) Febrile neutropenia (9)RR: 83% CR: 36% 3-yr PFS: 32%3-yr OS: 42%Inoperable patients. RT was delivered with IMRT technique
Wang[50]2018/ Phase I/II73S-1 + RT Various adjuvant CT before or after RT37.6 moNausea (9.6) Vomiting (5.7) Anorexia (9.6) Esophagitis (3.8) Stomatitis (1.9) Fatigue (1.9) Leukopenia (11.5) Neutropenia (3.8)3-yr LRFS: 92.2%3-yr OS: 70%MTD: S-1 80 mg/m2