TABLE 1.
Study characteristics.
| Included studies | Study type | Country | Stage | Regimen | Sample n | History of prior chemotherapy n (%) | PPI n (%) | PPI use window | Age, mean or median (SD or IQR) | ECOG | Follow-up* (months) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Capecitabine-based | |||||||||||
| Bridoux et al (2022) | Retrospective | France | I ∼ III | CapeOx | 215 | 0 (0) | 25 (11.6) | During Rx | PPI+: 61 (56–71) PPI-: 62 (54–69) | N/A | 60 |
| Kitazume et al. (2022) | Retrospective | Japan | II ∼ III | Capecitabine CapeOx | 449,157 | N/A | 29 (6.5) 25 (15.9) | 20% overlapping Rx | PPI+: 63 (58–70) PPI-: 64 (57–71) PPI+: 61 (55–66) PPI-: 60 (51–67) | N/A | 60 |
| Wong et al. (2019) | Retrospective | Canada | II ∼ III | CapeOx | 214 | 0 (0) | 50 (23.4) | During Rx | 59.5 (10.1) | N/A | 36 |
| Rhinehart et al. (2019) | Retrospective | United States | I ∼ IV | Capecitabine | 70 | 23 (32.9) | 15 (21.4) | 20% overlapping Rx | PPI+: 65 (26) PPI-: 73 (24) | N/A | 72 |
| Wang et al. (2017) | Retrospective | China | IV | CapeOx | 364 | 0 (0) | 215 (59.1) | During Rx | PPI+: 51.9 (N/A) PPI-: 51.2 (N/A) | N/A | 60 |
| Zhang et al. (2017) | Retrospective | China | II ∼ III | CapeOx | 125 | 0 (0) | 63 (50.4) | During Rx | 55.8 (12) | N/A | 60 |
| Sun et al. (2016) | Retrospective | Canada | I ∼ III | Capecitabine | 298 | 0 (0) | 77 (26.0) | During Rx | PPI+: 68.1 (N/A) PPI-: 67.6 (N/A) | 0–2 | 60 |
| AXEPT (Xu et al., 2018) | RCT | China, Japan, and Korea | IV | mXELIRI | 239 | 239 (100) | 25 (10.5) | 20% overlapping Rx | 61 (52–67) | 0–2 | 36 |
| N016966 (Saltz et al., 2008) | RCT | Multiple a | IV | CapeOxCapeOx + BEV | 637,343 | 0 (0) 0 (0) | 96 (15.1) 52 (15.2) | During Rx | 61 (18–83) 61 (18–86) | 0–1 | 27.6 |
| Fluorouracil-based | |||||||||||
| Wong et al. (2019) | Retrospective | Canada | II ∼ III | FOLFOX | 175 | 0 (0) | 49 (28) | During Rx | 59.4 (11.3) | N/A | 36 |
| Wang et al. (2017) | Retrospective | China | IV | FOLFOX | 307 | 0 (0) | 259 (70.6) | During Rx | PPI+: 51.9 (N/A) PPI-: 51.3 (N/A) | N/A | 60 |
| HORIZON III (Schmoll et al., 2012) | RCT | Europe | IV | FOLFOX + BEV | 666 | 0 (0) | 87 (13.0) | During Rx | 60 (22–88) | 0–1 | N/A |
| N016966 (Saltz et al., 2008) | RCT | Multiple a | IV | FOLFOX FOLFOX + BEV | 629,329 | 0 (0) 0 (0) | 120 (19.1) 46 (14.0) | During Rx | 60 (26–83) 60 (19–82) | 0–1 | 27.6 |
| AXEPT (Xu et al., 2018) | RCT | China, Japan, and Korea | IV | FOLFIRI | 243 | 243 (100) | 24 (9.9) | 20% overlapping Rx | 60 (51–68) | 0–2 | 36 |
| Carrato et al. (2013) | RCT | Multiple b | IV | FOLFIRI | 348 | 0 (0) | 39 (11.0) | During Rx | PPI+: 59 (52–66) PPI-: 58 (51–65) | 0–1 | N/A |
| VELOUR (Van Cutsem et al., 2012) | RCT | Multiple | IV | FOLFIRI | 584 | 584 (100) | 105 (18.0) | During Rx | PPI+: 59 (52–66) PPI-: 58 (51–65) | 0–2 | 22.28 |
| RAISE (Tabernero et al., 2015) | RCT | Multiple d | IV | FOLFIRI FOLFIRI + RAM | 477,469 | 477 (100) 469 (100) | 124 (26.0) 108 (23.0) | During Rx | PPI+: 61 (55–70) PPI-: 61 (54–68) | 0–1 | 21.7 |
| AVF2107g (Hurwitz et al., 2004) | RCT | Multiple e | IV | IFL IFL + BEV | 394,386 | 0 (0) 0 (0) | 67 (17.0) 89 (23.1) | During Rx | PPI+: 59 (52–65) PPI-: 60 (52–69) | 0–1 | N/A |
| Post hoc analysis of RCTs | |||||||||||
| Kichenadasse et al. (2021) Post hoc analysis of trials of N016966, Carrato 2013, VELOUR, RAISE, and AVF2107g | |||||||||||
| Kim et al. (2021) | Post hoc analysis of AXEPT trial | ||||||||||
Abbreviations: PPI, proton pump inhibitors; SD, standard deviation; IQR, interquartile range; ECOG, eastern cooperative oncology group; CapeOx, capecitabine + oxaliplatin; Rx, treatment; N/A, non-available.
RCT, randomized controlled trial; mXELIRI, capecitabine + irinotecan; BEV, bevacizumab; FOLFOX, folinic acid, fluorouracil, and oxaliplatin; FOLFIRI, leucovorin, fluorouracil, and irinotecan.
RAM, ramucirumab; IFL, irinotecan, leucovorin, and fluorouracil.
United States, South America, Canada, Europe, Australia, New Zealand, China, Hong Kong, Taiwan Korea, Thailand, Turkey, South Africa, and Israel.
Europe, Asia-Pacific, Africa, South America, and Canada.
United States, South America, Europe, Russia, Turkey, and South Africa.
United States, South America, Europe, Australia, India, Israel, Korea, Japan, and Taiwan.
United States, Australia, and New Zealand.