Table 1.
Chemotherapy in P-NETs: results from phase III and selected phase II trials
| Author | Phase | N total (P-NETs*) |
Treatment | ORR (%) | mPFS (months) | mOS (months) |
|---|---|---|---|---|---|---|
| Classical regimens based on STZ, DOXO and DTIC | ||||||
|
Moertel et al 1980 [11] |
III | 84 | STZ + 5-FU vs STZ | 63.0 vs 36.0 | NR |
26.0 vs 16.5 (P = ns) |
|
Moertel et al 1992 [12] |
III | 105 |
STZ + DOXO vs STZ + 5-FU vs CTZ |
69.0 vs 45.0 vs 30.0 ( P = 0.005) |
20.0 vs 6.9 vs NR b ( P < 0.001) |
26.4 vs 16.8 vs 18 (P < 0.004) |
|
Meyer et al 2014 [13] |
II | 86 (41) |
STZ + CAP vs STZ + CAP + CDDP |
12 vs. 16 a |
10.2 vs 9.7 a (HR 0.74/P = NR) |
26.7 vs 27.5 a (HR 1.16/P = NR) |
| Ramanathan RK et al. 2001[15] | II | 52 | DTIC (high dose) | 34.0 | NR | 19.3 |
|
Bajetta E. et al 1998 [17] |
II | 30 (15) | DTIC + 5-FU + EPI | 27.0 | NR | Not reached |
| Bajetta E et al. 2002 [16] | II | 82 (28) | DTIC + 5-FU + EPI | 24.4 a | 21.0 a/b | 38.0 a |
|
Ducreux et al 2014 [14] |
II | 34 | BEVA + 5-FU + STZ | 52.0 | 26.3 | Not reached |
| Temozolomide and Capecitabine based regimens | ||||||
| Pamela L. Kunz et al. 2018 [31] | II | 144 | CAPTEM vs TEM | 33.3 vs 27.8 |
22.7 vs 14.4 (HR 0.58/P = 0.023) |
Not reached vs 38.0 (HR 0.41/P = 0.012) |
| Pavlakis N et al. 2020 [36] | II | 28 | CAPTEM vs 177Lu-Octreotate + CAPTEM | 33.3 vs 66.7 | NR | NR |
| Claringbold P.G et al. 2016 [35] | II | 30 | CAPTEM + 177Lu-Octreotate | 80.0 | 48.0 | Not reached |
|
Fine et al 2014 [50] |
II | 28 (11) | CAPTEM | 36.0 | Not reached | Not reached |
|
Kulke et al 2006 [20] |
II | 29 (11) | TEM + Thalidomide | 45.0 | Not reached | Not reached |
|
Chan JA et al 2012 [21] |
II | 34 (15) | TEM + BEVA | 33.0 | 14.3 | 41.7 |
|
Chan JA et al 2013 [22] |
I/II | 40 | TEM + EVE | 40.0 | 15.4 | Not reached |
| Platinum, 5-FU or other cytotoxic-based regimens | ||||||
|
Moertel et al 1991 [41] |
II | 45 (14) | CDDP + VP-16 | 14.0 | 4.0 | 15.5 |
| Fjällskog ML et al. 2001 [42] | II | 36 (11) | CDDP + VP-16 | 27.0 | NR | 13.0 (including 11 NETs + 4 NECs) |
|
Bajetta et al 2007 [43] |
II | 27 (11) | XELOX | 27.3 | 20.0 a/b | 40.0 a |
|
Kunz PL et al 2016 [44] |
II | 16 | XELOX + BEVA | 18.8 | 15.7 | 38.0 |
|
Kunz PL et al 2016 [44] |
II | 12 | FOLFOX + BEVA | 50.0 | 21.0 | 31.0 |
|
Berruti et al 2014 [51] |
II | 45 (19) | CAP + BEVA + OCT | 26.3 | 14.3 | Not reached |
|
Ducreux et al 2006 [39] |
II | 20 (10) | FOLFIRI | 10.0 | 5.0 a | 15.0 a |
| Brixi-Benmansour et al. 2011[38] | II | 20 | FOLFIRI | 5.0 | 9.1 | NR |
|
Grande et al 2019 [45] |
II | 17 | SUN + EVO | 17.6 | 10.38 | Not reached |
BEVA Bevacizumab, CAP capecitabine, CAPTEM capecitabine-temozolomide, CDDP cisplatin, CTZ chlorozotocin, DOXO doxorubicin, DTIC dacarbazine, EPI epirubicin, EVE everolimus, EVO Evofosfamide, FOLFIRI 5-fluorouracile- Irinotecan, FOLFOX 5-fluorouracile-oxaliplatin, m months, mOS median overall survival, mPFS median progression free survival, NETs neuroendocrine tumors, NECs neuroendocrine carcinomas, NR not reported, ns non signicant, OCT octreotide, ORR objective response rate, P-NETs pancreatic neuroendocrine tumors, STZ streptozocin, SUN, TEM temozolomide; VP-16 etoposide, y years, XELOX capecitabine-oxaliplatin
*If more histologies included
a In the entire cohort, not specific of P-NETs
bTTP time to tumor progression