Table 2.
Summary of selected clinical trials for unresectable or advanced NETs
| Drug tested | Key targets |
N=Total patients N=carcinoid/PNET |
Octreotide or LAR | PR carcinoid PNET | SD carcinoid PNET | PD carcinoid PNET | PFS (median) carcinoid PNET | Reference |
|---|---|---|---|---|---|---|---|---|
| Octreotide LAR | Somatostatin receptor | N=42 LAR N=43 placebo |
vs Placebo | N=1/85 | 38% LAR 5% placebo | 62% LAR 95% placebo | 14.3 months (LAR) vs 6 months | Rinke et al., 2009 |
| Octreotide with/without IFN-α | Somatostatin receptor IFN-αR | N=68 carcinoid only | All | 0% | 82% (27/33) combination 46% (16/35) Octreotide alone |
18% (6/33) combination 54% (19/35) Octreotide alone |
NA | Kolby et al., 2003 |
| IFN-γ | IFN-γR | N=48 | Not allowed | 6% (N=3) | 58% (N=28) | 31% (N=15) | 5.5 months | Stuart et al., 2004 |
| Bortezomib | 26S Proteasome | N=16 N=12/4 | Allowed N=6 | 0% | 69% (N=11) | 31% (N=5) | NA | Shah et al., 2006 |
| Thalidomide | TNF-α | N=18 N=9/5 | Allowed | 0% | 69% (N=11) | 31% (N=5) | 7 months | Varker et al., 2008 |
| Imatinib | Abl; c-kit; PDGFR-α/β | N=27 carcinoid only | Allowed N=17 | 3.7% (N=1) | 83% (N=17) | 33% (N=9) | 5.9 months | Yao et al., 2007 |
| Endostatin | Vascular endothelium | N=42 N=20/22 | Allowed | 0% | 80% (N=32) | 20% (N=8) | 7.6 months, 5.8 months | Kulke et al., 2006a, b, c |
| Temozolamide and thalidomide | Cytotoxic; TNF-α | N=26 N=15/11 | Allowed N=11 | 7% (N=1) 45% (N=5) |
68% (N=19) | 7% (N=2) | Not reached | Kulke et al., 2006a, b, c |
| Temsirolimus | MTOR |
N=36 N=21/15 |
Allowed N=9 | 4.8% (N=1) 6.7% (N=1) |
57% (N=12) 60% (N=9) |
29% (N=6) 27% (N=4) |
6 months, 10.6 months | Duran et al., 2006 |
| Everolimus | MTOR |
N=60 N=30/30 |
All | 17% (N=5) 27% (N=8) |
80% (N=24) 70% (N=18) |
3% (N=1) 13% (N=4) |
15.7 months, 12.5 months | Yao et al., 2008 |
| Sunitinib | VEGFR 1–3 PDGFR-α/β |
N=107 N=41/66 |
Allowed (N=22/18) | 2.4% (N=1) 17% (N=11) |
83% (N=34) 68% (N=45) |
2.4% (N=1) 7.6% (N=5) |
10.2 months, 7.7 months | Kulke et al., 2008 |
| Bevacizumab and IFN-α | VEGF; IFN-αR | N=44 carcinoid only | All | 18% (Bevacizumab) 0% (INF-α) | 77% (Bevacizumab) 68% (INF-α) | 5% | 15.7 months | Yao et al., 2008 |
Abbreviations: Abl, Abelson oncogene; IFN, interferon; LAR, long-acting repeatable; MTOR, mammalian target of Rapamycin; NA, not available; NETs, neuroendocrine tumors; PDGFR, platelet-derived growth factor receptor; PFR, progression-free rate; PNET, pancreatic neuroendocrine tumor; PR, partial remission; SD, stable disease; TNF, tumor necrosis factor; VEGFR, vascular endothelial growth factor receptor.