Table 4.
The main phase I/II trials in gastric cancer that evaluate the postoperative therapy
| Trial | Year/type | N° of patients | Treatment schedule | Median FU | Severe toxicity | Clinical efficacy | Survival | Limits/ characteristics |
| Michel[37] | 2014/Phase I | 21 | FOLFIRIx4→RCT | 26.6 mo | During FOLFIRI (23.8) During RT (9.5) | Median PFS: 22.8 mo | Median OS: 32.9 mo | Parallel study with a neoadjuvant schedule (see above). Study closed for futility (42.9% completed the schedule) |
| Wang[41] | 2014/ Phase I | 18 | 5FU + RT→FOLFOX4 (8) FOLFOX4→5FU+RT (7) 5FU + RT (3) | 45 mo | Nausea (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 II | 30 | FOLFOX6x2→5FU + RT | 21 mo | Nausea (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 II | 110 | FOLFOXx1→FOLFOXd1, 22 + RT→FOLFOXx5 | 43 mo | Nausea 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 I | 21 | SOXx1→S-1 + RT | 26 mo | Nausea (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 II | 46 | SPx1→S-1 + RT→SPx2 | 56.5 mo | Nausea (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/II | 55 | 5FU-CDDP + RT | 36.4 mo | Hematological (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 II | 55 | mDCFx2→TXL + RT→ mDCFx2 | 61 mo | Nausea (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 II | 36 | mDCFx2→wTXL + RT→mDCFx2 | 35.6 mo | Nausea (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/II | 73 | S-1 + RT Various adjuvant CT before or after RT | 37.6 mo | Nausea (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 |
CRT: Chemoradiotherapy; RT: Radiotherapy; CR: Complete response; OS: Overall survival; NR: Not reported; MTD: Maximum tolerated dose; PD Progressive disease; DFS: Disease-free survival; PFS: Progression-free survival; LRC: Loco-regional control; RFS: Relapse-free survival; RR: Response rate; LRFS: Local relapse-free survival.