Table 2.
Chemotherapy in EP-NETs: results from phase III and selected phase II trials
| Author | Phase | N (GI/L) | Treatment | ORR (%) | mPFS (months) | mOS (months) |
|---|---|---|---|---|---|---|
| Classical regimens based on STZ, DOXO and DTIC | ||||||
|
Moertel et al 1979 [52] |
III | 118 (50/17) | STZ + 5-FU vs STZ + CTX | 33.0 vs 26.0 (GI: 36.4 vs. 37.5/L: 28.6 vs 0.0) | NR | 11.2 vs 12.5 |
| Engstrom et al.1984 [53] | II/III | 172 (85/18) | 5-FU + STZ vs DOXO | 22.0 vs 21.0 | NR |
16.0 vs 12.0 (P = ns) |
|
Sun et al 2005 [54] |
II/III | 176 (55/22) | DOXO + 5FU vs STZ + 5-FU |
15.9 vs 16.0 (P = ns) |
4.5 vs 5.3 (P = ns) |
15.7 vs 24.3 (P = 0.027) |
|
Sun et al 2005 [54] |
II/III | 61 (21/11) | DTIC | 8.2 | NR | 11.9 |
|
Dahan et al 2009 [55] |
III | 64 (42/3) | INFα-2A vs STZ + 5FU | 9.0 vs 3.0 |
14.1 vs 7.3 (HR 0.75/P = 0.25) |
44.3 vs 30.4 (P = 0.83) |
|
Bokowski et al 1994 [56] |
II | 56 (28/7) | DTIC | 15.0 | NR | 20.0 |
|
Bajetta E. et al 1998 [17] |
II | 30 (6/3) | DTIC + 5-FU + EPI | 30.0 (GI:17.0/L: NR) | Not reached | Not reached |
| Bajetta E et al. 2002 [16] | II | 82 (17/7) | DTIC + 5-FU + EPI | 24.4 (L:14.0) | 21.0 b | 38.0 |
|
Meyer et al 2014 [13] |
II | 86 (17/0) |
STZ + CAP vs STZ + CAP + CDDP |
12.0 vs 16.0 |
10.2 vs 9.7 (P = NR/HR 0.74) |
26.7 vs 27.5 (HR 1.16/P = NR) |
| Capecitabine and Temozolomide based combinations | ||||||
| Ferolla et al. 2020 [61] | II | 40 (0/36) | LAN + TEM | 2.5 | 9.2 | Not reached |
|
Kulke et al 2006 [20] |
II | 29 (11a) | TEM + Thalidomide | 25 (7.0 a) | Not reached | Not reached |
|
Chan JA et al 2012 [21] |
II | 34 (19 a) | TEM + BEVA | 15 (0.0 a) | 11.0 (7.3 a) | 33.3 (18.8 a) |
|
Mitry et al 2014 [59] |
II | 49 (49/0) | CAP + BEVA | 18.0 | 23.4 | Not reached |
| Claringbold P.G et al. 2012 [34] | II | 35 (15/2) | CAPTEM + 177-Lu-Octreotate | 53.0 | 31.0 | Not reached |
|
Fine et al 2014 [50] |
II | 28 (0/12) | CAPTEM |
43.0 (L:41.0) |
Not reached | Not reached |
|
Berruti et al 2014 [51] |
II | 26 (13/8) | CAP + BEVA + OCT | 11.5 |
14.9 (GI:14.3/L: 18.6) |
Not reached (L: 38.0) |
| Pavlakis et al. 2020 [36] | II | 47 (47/0) | CAPTEM + PRRT vs. PRRT | 31.3 vs 15.4 | Not reached | Not reached |
| Platinum-based regimens | ||||||
| Moertel et al. 1991 [41] | II | 27 (13a) | CDDP + VP-16 | 7.0 (0.0a) | NR (3.0a) | 15.0 (10.5a) |
| Fjällskog ML et al. 2001 [42] | II | 36 (3/18) | CDDP + VP-16 |
36.0 (GI:33.0/L: 39.0) |
NR |
19.0 (GI:10/L:26.0) |
|
Bajetta et al 2007 [43] |
II | 27 (8/5) | XELOX |
30,0 (GI:0.0/L: 60.0) |
20.0 b | 40.0 |
|
Kunz PL et al 2016 [44] |
II | 20 | XELOX + BEVA | 5.0 | 19.1 | 42.2 |
|
Kunz PL et al 2016 [44] |
II | 22 | FOLFOX + BEVA | 18.0 | 19.3 | 33.1 |
BEVA Bevacizumab, CAP capecitabine, CAPTEM capecitabine-temozolomide, CDDP cisplatin, CTX cyclophosphamide, DOXO doxorrubicin, DTIC dacarbazine, EPI epirubicin, EVE everolimus, FOLFOX 5-fluorouracile-oxaliplatin, GI gastrointestinal, L lung, LAN lanreotide autogel, m months, mOS median overall survival, mPFS median progression free survival, NR not reported, ns non signicant, OCT octreotide, ORR objective response rate, PRRT peptide receptor radionuclide therapy, STZ streptozocin, TEM temozolomide, VP-16 etoposide, XELOX capecitabine-oxaliplatin, 5-FU 5-fluorouracil
aEP-NETs or carcinoids not otherwise specify
bTTP time to tumor progression