Table 3.
Chemotherapy in NECs: Prospective and selected retrospective studies
| Author | Type of study | N | Primary site | Treatment | ORR (%) | mPFS (months) | mOS (months) |
|---|---|---|---|---|---|---|---|
| First line | |||||||
| Moertel et al. 1991 [41] | II | 18 | GEP (14)/L (1)/U(3) | CDDP + VP-16 | 67.0 | 11.0 | 19.0 |
| Hainsworth et al. 2006 [79] | II | 78 | GEP (15)/L (7)/U (48)/ other (8) | Paclitaxel + CBDCA + VP-16 | 53.0 | 7.5 | 14.5 |
| Bajetta et al. 2007 [43] | II | 13 | GEP (5)/L (5)/ other (3) | XELOX | 23.0 | 4.0 b | 5.0 |
| Mani et al. 2008 [86] | II | 20 | NEC (NR) | CDDP + IRI | 58.0 | 4.0 b | NR |
| Alifieris et al. 2020 [89] | II | 22 | GI | CAPOXIRI-BEVA PAZO + CAPE | 47.4 | 13.0 | 29.0 |
| Walter T et al. 2017 [75] | NTR(RENATEN, FFCD,TENpath) | 152 | GEP/U |
CDDP + VP-16 (113) CBDCA + VP-16 (39) |
50.0 | 6.2 | 11.6 |
| Mitry et al. 1999 [70] | Retrospective | 41 |
GEP (20)/L (10)/ HN (4)/ U (7) |
CDDP + VP-16 | 41.5 | 8.9 | 15.0 |
| Iwasa et al. 2010 [71] | Retrospective | 21 | P (10)/ HB (11) | CDDP + VP-16 | 14.0 | 1.8 | 5.8 |
| Sorbye et al. 2013 [69] |
NTR (NORDIC) |
252 | GEP (174)/ U (78) |
CDDP + VP-16 (129) CBDCA + VP-16 (67) CBDCA + VP-16 + VINC(28) |
31.0 30.0 44.0 |
4.0 4.0 4.0 |
12.0 11.0 10.0 |
| Yamaguchi, 2014 [74] | Retrospective | 206 | GEP |
CDDP + VP-16 (46) CDDP + IRI (160) |
28.0 50.0 |
4.0 5.2 |
7.3 13.0 |
| Frizziero et al. 2019 [76] | Retrospective | 98 | GEP (72)/ U (26)/ other a | CBDCA + VP-16 | 47.9 | 6.0 | 11.5 |
| Jimenez-Fonseca et al. 2020 [78,100] | NTR (RGETNE) | 279 | GEP (70%) U (16%) | CDDP/CBDCA + VP-16 | 73.0 | 6.1 | 14 |
| Okita et al. 2011 [82] | Retrospective | 12 | Gastric | CDDP + IRI | 75.0 | 7.0 | 22.6 |
| Nakano et al. 2012 [84] | Retrospective | 28 | GEP (9)/ U (12)/ others (23)a | CDDP + IRI | 64.0 | 7.3 | 16.0 |
| Ramella et al. 2013 [81] | Retrospective | 28 | GEP (19)/ U (6)/ others (2) |
CDDP + IRI (25) CBDCA + IRI (3) |
46.0 | 3.7 b | 11.7 |
| Lu et al. 2013 [85] | Retrospective | 16 | GEP | CDDP + IRI | 57.1 | 5.5 | 10.6 |
| Okuma et al. 2014 [83] | Retrospective | 12 | Esophageal | CDDP + IRI | 50.0 | 4.0 | 12.6 |
| Second line and beyond | |||||||
| Kobayashi et al. 2021 [95] | II | 13 | GEP (10)/ U (1)/ other (2) | TEM | 15.4 | 1.8 | 7.8 |
| Walter T et al. 2017 [75] | NTR(RENATEN, FFCD,TENpath) | 105 | GEP and U |
FOLFIRI (72) FOLFOX (33) |
24.0 16.0 |
2.9 2.3 |
5.9 3.9 |
| Welin T et al. 2011 [93] | Retrospective | 25 | GEP (17)/ L (3)/ U (5) | TEM ± CAPE ± BVZ | 33.0 | 6.0 | 22.0 |
| Olsen et al. 2012 [94] | Retrospective | 28 | GEP (18)/ L (1)/ U (6) | TEM | 0.0 | 2.4 | 3.5 |
| Hentic et al. 2012 [90] | Retrospective | 19 | GEP | FOLFIRI | 31.0 | 4.0 | 18.0 |
| Sorbye et al. 2013 [69] | Retrospective | 100 | GEP and U | Various (35% TEM, 20% taxanos…) | 18.0 | NR | 19.0 |
| Ferrarotto et al. 2013 [91] | Retrospective | 24 | GEP (18)/ L (4)/ U (2) | XELOX | 29.0 | 9.8 b | Not reached |
| Hadoux et al. 2015 [92] | Retrospective | 20 | GEP (12)/ L (4)/ U (2)/ other (2) | FOLFOX | 29.0 | 4.5 | 9.9 |
| Yamaguchi, 2014 [74] | Retrospective | 116 | GEP/ HB |
Amrubicin CCDP or CBDCA + VP-16 IRI S-1 CDDP + IRI |
4.0 17.0 5.0 27.0 40.0 |
1.9 1.9 2.2 2.4 4.8 |
8.0 5.0 6.0 12.0 9.0 |
|
Frizziero et al. 2019 [76] |
Retrospective | 17 | GEP/ U/ other a | CBDCA + VP-16 | 23.5 | 4.5 | 12.5 |
BEVA Bevacizumab, CAPE capecitabine, CAPOXIRI Capecitabine, Oxaliplatin Irinotecan, CBDCA carboplatin, CDDP cisplatin, FFCD Fédération Francophonede Cancérologie Digestive, FOLFIRI 5-Fluorouracile-irinotecan, FOLFOX 5- Fluorouracile-oxaliplatin, GI gastrointestinal, GEP gastroenteropancreatic, HB hepatobiliary, HN head and neck, IP Irinotecan-platinum, IRI Irinotecan, L lung, MANEC Mixed adenoneuroendocrine carcinoma, mOS median overall survival, mPFS median progression free survival, NEC neuroendocrine carcinoma, NR not reported, NTR national tumor registry, ORR overall response rate, OS overall survival, PAZO Pazopanib, PFS progression free survival, RENATEN Groupe d’étude des Tumeurs Endocrines [GTE], RGETNE Registro del grupo español de tumores neuroendocrinos, TENpath Réseau national d’expertise pour le diagnostic anatomopathologique des tumeurs neuroendocrines de l’adulte, familiales et sporadiques, TTP time to tumor progression, U unknown, VINC vincristine, VP-16 etoposide, XELOX capecitabine + Oxaliplatin
aData from the entire cohort, no specific of the subgroup
bTTP time to tumor progression