Table 5.
Clinical trials of cytotoxic chemotherapy for GEP-NEC
| Study | Primary sites | No. of pts | Regimen | ORR (%) | mPFS (months) | mOS (months) | Ref |
|---|---|---|---|---|---|---|---|
| First-line cytotoxic chemotherapy | |||||||
| Retro | Any | 41 | CDDP + ETP | 42 | 8.9 | 15 | [107] |
| Pros | Any | 18 | CDDP + ETP | 67 | 8 | 19 | [108] |
| Retro | HBP | 21 | CDDP + ETP | 14 | 1.8 | 5.8 | [109] |
| Retro | GEP | 19 | CBDCA + ETP | 47 | 7.0 | 12.7 | [110] |
| Retro | Extrapulmonary | 106 | CBDCA + ETP | 48 | 6.0 | 11.5 | [111] |
| Retro | GEP or UK | 21 | Platinum + ETP | 52 | 7 | 16 | [112] |
| Retro | GEP | 113 | Platinum + ETP | 35 | 5.0 | 16.4 | [19] |
| Pros | GEP | 152 | Platinum + ETP | 50 | 6.2 | 11.6 | [21] |
| Retro | GEP | 236 | Platinum + ETP | 27 | 4.6 | 13 | [83] |
| Phase II | Extrapulmonary | 78 | CDDP + ETP + PTX | 53 | 7.5 | 14.5 | [113] |
| Phase II | Any | 20 | CDDP + CPT-11 | 58 | 4 | - | [114] |
| Retro | Gastric | 22 | CDDP + CPT-11 | 75 | 7.1 | 22.6 | [115] |
| Retro | Extrapulmonary | 28 | CDDP + CPT-11 | 64 | 6.4 | 16 | [116] |
| Retro | Esophageal | 12 | CDDP + CPT-11 | 50 | 4.0 | 12.6 | [117] |
| Retro | GEP | 16 | CDDP + CPT-11 | 57 | 5.5 | 10.6 | [118] |
| Retro | Extrapulmonary | 28 | CDDP + CPT-11 | 46 | 3.7 | 11.7 | [119] |
| Phase II | GEP | 40 | CDDP + CPT-11 + Oct-LAR | 45 | 5.7 | 12.9 | [120] |
| Retro | Pancreatic | 29 | Platinum-based regimen | 37 | - | 10.1 | [121] |
| Retro | GEP | 160 | CDDP + CPT-11 | 50 | 5.2 | 13.0 | [82] |
| 46 | CDDP + ETP | 28 | 4.0 | 7.3 | |||
| Retro | GEP | 252 | Platinum-based regimen | 31 | 4 | 11 | [14] |
| 129 | CDDP + ETP | 31 | 4 | 12 | |||
| 67 | CBDCA + ETP | 30 | 4 | 11 | |||
| 28 | CBDCA + VCR | 44 | 4 | 10 | |||
| rPhase II | GEP | 33 | CDDP + ETP | 42 | 6.4 | 11.3 | [122] |
| 33 | CDDP + CPT-11 | 42 | 5.8 | 10.2 | |||
| Phase III | GEP | 84 | CDDP + ETP | 55 | 5.6 | 12.5 | [81] |
| 86 | CDDP + CPT-11 | 53 | 5.1 | 10.9 | |||
| Retro | GEP | 11 | FOLFIRI | 64 | 6.5 | 13.0 | [123] |
| Second- or later-line cytotoxic chemotherapy | |||||||
| Pros | GEP | 72 | FOLFIRI | 24 | 2.9 | 5.9 | [21] |
| Retro | GEP | 19 | FOLFIRI | 31 | 4 | 18 from diagnosis | [124] |
| Retro | GEP | 5 | FOLFIRI | 40 | 5.8 | 11 | [125] |
| Pros | GEP | 33 | FOLFOX | 16 | 2.3 | 3.9 | [21] |
| Retro | Any | 20 | FOLFOX | 29 | 4.5 | 9.9 | [126] |
| Phase II | Any | 13 | XELOX | 23 | 4 | 5 | [127] |
| Retro | GEP or UK | 28 | TEM | 0 | 2.4 | 3.5 | [128] |
| Retro | Any | 25 | TEM ± cape ± Bev | 33 | 6 | 22 | [129] |
| Retro | GEP | 12 | TEM + cape | 8 | 3.3 | 4.6 | [130] |
| Retro | GEP | 46 | TEM + cape or TEM mono | 26 | 2 | 13.1 | [87] |
| Retro | GEP | 84 | TEM-based or taxan-based | 18 | - | 19 from 1st line | [14] |
| Retro | GEP | 10 | AMR | 20 | 2.6 | 5.0 | [131] |
| Retro | GEP | 13 | AMR | 39 | 3.6 | 7.2 | [132] |
| Retro | GEP | 19 | AMR | 19 | 3.8 | 7.7 | [133] |
| Retro | GEP | 16 | AMR | 6 | 2.9 | 13.8 | [134] |
| Retro | Any | 30 | TPT | 7 | 2.1 | 4.1 | [135] |
| Retro | GEP | 22 | TPT | 0 | 2.1 | 3.2 | [136] |
| Phase II | GEP | 23 | Lipotecan | 0 | 1.8 | 4.3 | [137] |
| rPhase II | Extrapulmonary | 29 | nal-IRI/5-FU | 10 | 3 | 9 | [138] |
| 29 | DTX | 10 | 2 | 5 | |||
Some of studies included heterogeneous populations of well-differentiated G3 NET and poorly-differentiated G3 NEC
Abbreviations: GEP, gastro-entero-pancreatic; NEC, neuroendocrine carcinoma; HBP, hepatobiliary pancreatic; UK, unknown; ORR, overall response rate; mPFS, median progression-free survival; mOS, median overall survival; Pts, patients; Ref, reference; Retro, retrospective study; Pros, prospective study; rPhase II, randomized phase II; Oct-LAR, octreotide long acting release; CDDP, cisplatin; CBDCA, carboplatin; CPT-11, irinotecan; ETP, etoposide; VCR, vincristine; PTX, paclitaxel; FOLFOX, 5-fluorouracil + leucovorin + oxaliplatin; FOLFIRI, 5-fluorouracil + leucovorin + irinotecan; XELOX, capecitabine + oxaliplatin; TEM, temozolomide; Bev, bevacizumab; Cape, capecitabine; Mono, monotherapy; AMR, amrubicin; TPT, topotecan; DTX, docetaxel; nal-IRI, nanoliposomal irinotecan; Lipotecan, a novel camptothecin analog