Table 1.
Characteristics of Trials Included in the Review
| First Author, Year of Publication | Type of the Study | Treatment Regimen | Patients (N) | Median Age, y | Site of Primary Tumor | Histotypes (WHO) | Line of Treatment (I or > I Line) | Duration of Treatment |
|---|---|---|---|---|---|---|---|---|
| Fine, 200535 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 1500 mg/m2 1–14 | 10 ˜6 | -- | GI NET, panNET, lung, others | WD NET | >I line | -- |
| Isacoff, 200636 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 1000 mg/m2 BID 1–14 | 17 §16 | 54 | panNET | NET | >I line | -- |
| Strosberg 201137 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 30 | 58 | panNET | NET G1-G2 | >/= I line | 11 pts until PD, 15 until treatment break (non-specified) |
| Welin, 201138 | Retrospective | TEM 150 mg/m2 10–14 + CAP 750–1000 mg/m2 BID 1–14 | 25 | 55 | GI NET, panNET, lung, unknown | NEC, atypical carcinoid (ki-67>20%) | >I line | -- |
| Claringbold, 201274 | Phase I–II | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 35 *34 | 63 | GI NET, panNET, lung | WD NET | >/= I line | 4 cycles |
| Ganetsky, 201239 | Retrospective | -- | 20 | 64 | GI NET, panNET, lung, others | NET G1-G2-G3 | >I line | -- |
| Fine, 201340 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 600 mg/m2 BID 1–14 | 18 | 54 | GI NET, panNET | WD NET | >I line | Until PD |
| Oberstein, 201341 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 1000 mg/m2 BID 1–14 | 18 | 55 | GI NET, panNET, others | NET G1-G2 (Ki67<10%) | >I line | -- |
| Abbasi, 201442 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 600 mg/m2 BID 1–14 | 21 | 47 | panNET, GI NET | WD NET (Ki67<10) | >I line | Until PD or death |
| Fine, 201443 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 1500 mg/m2 1–14 | 28 | -- | GI NET, panNET, lung, others | WD NET (ki-67 ≤20%) | >I line | -- |
| Ramirez, 201544 | Retrospective | -- | 30 | 58.5 | GI NET, panNET, lung, others | NET | -- | > 1 cycle |
| Spada, 201523 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 1500 mg/m2 BID 1–14 | 58 | 58 | GI NET, panNET, lung, unknown | NET G1-G2-G3, typical, atypical carcinoid | >I line | -- |
| Chaves, 201645 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 10 | 59 | GI NET, panNET | NET G1-G2-G3 | >/= I line | -- |
| Cives, 201646 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 143 | 59 | panNET | NET G1-G2-G3 | >/= I line | 9 cycles (median number) |
| Claringbold, 201675 | Phase I–II | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 30 | 60 | panNET | NET G1-G2 | >I line | 4 cycles (8 weeks) |
| Crespo, 201647 | retrospective | -- | 25 †21 | 56 | GI NET, panNET, lung, others | NEN (60% Ki67≤50%) | >/= I line | -- |
| Ramirez, 201648 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 29 | 58 | GI NET, panNET, lung | NET G1-G2-G3 | -- | 1 cycle at least |
| Crespo, 201749 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 65 | 62 | GI NET, panNET, lung, others | NET G1-G2 | >/= I line | 1 cycle at least |
| Lamarca, 201750 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 60 | 63.6 | GI NET, panNET, lung, others | NET G1-G2-G3 | >/= I line | 6 cycles |
| Owen, 201751 | Retrospective | TEM 200 mg/m2 10–14 + CAP 1500 mg/m2 1–14 | 38 #29 | 53 | panNET | NET G1-G2-G3 | >/= I line | At least 1 cycle (median number 4 cycles) |
| Chauhan, 201852 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 12 | 62 | unknown | NET G1-G2-G3, NEC | >/= I line | 6 cycles (median number) |
| Campana, 201853 | Retrospective | TEM 10–14 + CAP 1–14 | 95 | 62 | panNET, lung, others | NET G1-G2, NEC | >/= I line | 6 (1–45) cycles (median number) |
| Smiroldo, 201854 | Retrospective | TEM 75 mg/m2 BID 10–14 + CAP 600 mg/m2 BID 1–14 | 27 | 61 | GI NET, panNET, lung, others | NET | >/= I line | 6 (2–25) cycles (median number) |
| Soulen 201855 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 600 mg/m2 BID 1–14 | 21 °19 | 58 | GI NET, panNET, lung, unknown | NET G2 | >/= I line | -- |
| De Mestier, 201956 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 153 | 57.7 | GI NET, panNET | NET G1-G2-G3 | >/= I line | 6 cycles (median number) |
| Rogowski, 201957 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 600 mg/m2 BID 1–14 | 32 | 55 | GI NET | NET G3, NEC | >/= I line | -- |
| Sahu, 201958 | Retrospective | TEM 100 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 32 | 58 | GI NET, panNET, lung, unknown | NET G2-G3 | >/= I line | 6 (2–16) cycles (median number) |
| Yordanova, 201959 | Retrospective | TEM 150–250 mg/m2 10–14 + CAP 500–1000 mg/m2 BID 1–14 | 12 ‡ 11 | 54 | GI NET, panNET, others | NET G2-G3 | >/= I line | Until PD |
| Al Toubaah, 202060 | Retrospective | -- | 32 | -- | GI NET | -- | -- | 8 (0–73) months (median number) |
| Al Toubaah, 202061 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 20 | -- | lung | Typical, atypical NET, LCNEC | >/= I line | Until PD, max response, physician choice |
| Chatzellis, 202062 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 79 | 60 | GI NET, panNET, lung, tymic | NEN G1-G2-G3 | >/= I line | 12.1 (0.6–55.6) months (median number) |
| De Mestier, 202063 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 100 | 57 | panNET | NET G1-G2-G3 | >/= I line | 7 ± 4.5 cycles |
| Ostwal, 202064 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 29▯24 | 48 | GI NET, panNET | NET G2-G3 | >/= I line | 4 (1–15) cycles (median number) |
| Papaxoinis, 202065 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 33 | -- | lung | Typical, atypical carcinoid | >I line | 6 cycles (median number) |
| Squires, 202066 | Retrospective | TEM 200 mg/m2 10–14 + CAP 1500 mg/m2 1–14 | 30 | panNET | NET G1-G2-G3 | I line (neoadj) | ||
| Thomas, 202067 | Retrospective | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 116 | 56 | GI NET, panNET, lung, others, unknown | WD NET, NEC | >/= I line | 9.5 cycles (median number) |
| Wang W, 202068 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 750–850 mg/m2 BID 1–14 | 151 | 49 | GI NET, panNET, others, unknown | NET G1-G2-G3, NEC | >/= I line | 5 (2–44) cycles (median number) |
| Dogan, 202169 | Retrospective | -- | 43 | 59 | GI NET, panNET | WD NET, NEC | >I line | -- |
| Jeong, 202172 | Phase II | TEM 200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 30 | 55 | GI NET, panNET | NET G3, NEC | >/= I line | Until PD, max toxicity |
| Liu, 202170 | Retrospective | -- | 20 | 59.5 | GI NET, panNET, unknown | NET G3 | I line | -- |
| Spada, 202171 | Retrospective | TEM 150–200 mg/m2 10–14 + CAP 750 mg/m2 BID 1–14 | 114 | 59 | GI NET, panNET, lung, unknown | NET G1-G2-G3, NEC | >/= I line | Until PD, max toxicity |
| Zrajkowska, 202173 | Phase II | -- | 21“0 | 58.6 | panNET midgut |
NET G1-G2-G3 | >I line | -- |
Notes: *34 pts evaluated for response rate (RR); †21 pts evaluated for RR; ˜6 pts evaluated for RR; §16 pts evaluated for RR; ▯24 pts evaluated for RR; #29 pts evaluated for RR; °19 pts evaluated for RR; ‡ 11 pts evaluated for RR; “pts evaluated for RR.
Abbreviations: TEM, temozolomide; CAP, capecitabine; BID, bis in die; GI NET, gastrointestinal (non-pancreatic) neuroendocrine tumor; panNET, pancreatic neuroendocrine tumor; NEC, neuroendocrine carcinoma; G, histological grading; PD, progression disease; max, maximum.