Table 1.
Summary of octreotide LAR studies in acromegaly: study parameters and biochemical endpoints
| Publication | n | Trial design | Trial duration | Patient population | Dose titration | GH and IGF-1 entry criteria | Target threshold values for GH and IGF-1 | Biochemical control rates | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Previous treatment | Prior response to SSA | GH n (%) |
IGF-1 n (%) |
GH + IGF-1 n (%) |
|||||||
| Lancranjan et al. [8] | 101 | OL, P | 30 mo | TSS + oct sc (n = 101) | 83 pts were considered good responders to oct sc | Dose-ranging study: suppression of GH and IGF-1 assessed Biochemical control not defined |
55 (55)a | 66 (65)b | – | ||
| Davies et al. [7] | 13 | OL, P | 1–3 yr | TSS (n = 2); RT (n = 1); TSS + RT (n = 4); Y implant (n = 1); de novo (n = 5) | Pts not selected for prior response | Dose-ranging study: suppression of GH and IGF-1 assessed Biochemical control not defined |
6 (46)c | 7 (54)d | – | ||
| Lancranjan et al. [9] | 151 | OL, P | 12 mo | Oct sc (n = 49); TSS + oct sc (n = 56); RT + oct sc (n = 8); TSS + RT + oct sc (n = 38) | Only pts with GH < 10 µg/L during ≥4 wk treatment with oct sc were selected | Individualized according to the mean GH after the second dose | GH > 2 µg/L after OGTT and elevated IGF-1 | GH ≤ 2.5 µg/L IGF-1 normal |
104 (69) | 98 (65) | – |
| Colao et al. [5] | 36 | OL, P | 24 mo | TSS (n = 5); TSS + oct sc (n = 5); TSS + oct LAR (n = 3); TSS + lan SR (n = 8); de novo (n = 15) | 16/21 pts with previous surgery received oct sc | Uptitrated in 15 pts with GH > 5 µg/L | GH > 2 µg/L after OGTT and elevated IGF-1 for age | GH ≤ 2.5 µg/L IGF-1 normal |
20 (56) | 19 (53) | – |
| Cozzi et al. [6] | 110 | OL, Ret | 18–54 mo | TSS + oct LAR (n = 29); RT + oct LAR (n = 7); TSS + RT + oct LAR (n = 23); oct sc (n = 39); de novo (n = 12) | Pts had to have a GH and/or IGF-1 decrease of at least 20 % after a 6-month trial with oct LAR | Individualized to achieve normal age-adjusted IGF-1 levels and GH <2.5 µg/L | GH > 1 µg/L after OGTT and elevated IGF-1 for age | GH < 2.5 µg/L IGF-1 normal |
79 (72)e | 83 (75)e | – |
| Ayuk et al. [24] | 91f | OL, Ret | 48 wk | Oct sc (n = 34); TSS + oct sc (n = 29); RT + oct sc (n = 5); TSS + RT + oct sc (n = 23) | Only patients who completed 48 wk treatment were considered | Individualized according to the mean GH after the second dose | GH > 2 µg/L after OGTT and elevated IGF-1 | GH < 2.0 µg/L | 61 (67) | 48 (72) | – |
| Jallad et al. [25] | 80 | OL, P | 12 mo | TSS + oct LAR (n = 24); TSS + RT + oct LAR (n = 28); lan (n = 14); DA (n = 1); de novo (n = 13) | Pts not selected for prior response | Individualized to achieve normal age-adjusted IGF-1 levels | GH > 1 µg/L after OGTT and elevated IGF-1 for age and sex | GH < 2.5 µg/L IGF-1 normal |
34 (43) | 20 (25) | – |
| Cozzi et al. [12] | 67 | OL, P | 6–108 mo | De novo (n = 67) | Pts not selected for prior response | Individualized at 3- to 6-mo intervals if GH or IGF-1 levels remained elevated | GH > 1 µg/L after OGTT and elevated IGF-1 for age | GH < 2.5 µg/L IGF-1 normal |
46 (69)e | 47 (70)e | 38 (57)e |
| Colao et al. [11] | 56 | OL, Ret | 24 mo | De novo (n = 56) | 16 pts were excluded from the efficacy analysis because of lack of response before 24 mo | Uptitration in pts with IGF-1 levels above the normal range and/or GH > 2.5 mg/L | GH > 1 µg/L after OGTT and elevated IGF-1 for age | GH ≤ 2.5 µg/L IGF-1 normal |
48 (86) | 47 (84) | 45 (80) |
| Mercado et al. [18] | 98 | OL, P | 48 wk | De novo (n = 98) | Pts not selected for prior response | Uptitration in pts with GH > 2.5 μg/L or IGF-1 above the adjusted normal range at 4 and 6 mo | GH > 1 µg/L after OGTT and IGF-1 > 97th percentile of the normal range for age and sex | GH ≤ 2.5 µg/L IGF-1 normal |
30 (31) | 23 (23) | 17 (17) |
| Andries et al. [28] | 12 | OL, R, P, CO | 12 mo | TSS alone (n = 4); TSS + radiotherapy (n = 3); oct LAR (n = 11) | 4 pts had control of both GH and IGF-1 at study entry | – | – | GH < 0.38 µg/L IGF-1 normal |
5 (42) | 5 (42) | 4 (33) |
| Colao et al. [16] | 48 | OL, R, P | 48 wk | De novo (n = 48) | Pts not selected for prior response | Uptitration in pts with mean GH >2.5 μg/L and/or elevated IGF-1 at 3 and 6 mo | GH > 1 μg/L after OGTT and IGF-1 > 97th percentile for age and sex | GH ≤ 2.5 µg/L IGF-1 normal |
– | – | 13 (27) |
| Ghigo et al. [26] | 56 | OL, R, P | 12 mo | All pts naïve to medical therapy and RT; TSS in an unreported number of pts | Pts not selected for prior response | Uptitration in pts with IGF-1 within 20 % below ULN or > ULN every 16 wk | GH > 1 μg/L after OGTT and IGF-1 ≥ 1.3xULN | IGF-1 normal | – | 19 (34) | – |
| Oki et al. [27] | 30 | OL, Ret | 24 mo | TSS alone (n = 12); TSS + DA (n = 11); TSS + radiotherapy (n = 1); TSS + radiotherapy + DA (n = 5); de novo (n = 1) | Pts not selected for prior response | Uptitration in pts with mean GH >2.5 μg/L and/or elevated IGF-1 every 3 mo | – | GH ≤ 2.5 µg/L IGF-1 normal |
17 (57) | 16 (53) | 11 (37) |
| Karaca et al. [17] | 11 | R, P | 12 mo | De novo (n = 11) | Pts not selected for prior response | Dose titration according to biochemical response at 3, 6 and 12 mo | – | GH ≤ 2.5 µg/L IGF-1 normal |
9 (82) | 3 (27) | 3 (27) |
| Carlsen et al. [15] | 32 | R, P | 24 wk | De novo (n = 11) | Pts not selected for prior response | Fixed dose | GH > 5 mIU/L after OGTT | GH ≤ 2 mIU/L during OGTT IGF-1 ≤ ULN |
11 (34) | 10 (31) | 7 (22) |
| Tutuncu et al. [14] | 36 | OL, Ret | 18 mo | TSS (n = 36) | Pts not selected for prior response | Dose titration according to biochemical response at 6 mo | GH > 1 μg/L after OGTT or mean GH > 5 µg/L and IGF-1 > ULN for age and sex | GH ≤ 2.5 µg/L IGF-1 normal |
24 (67) | 24 (67) | 23 (64) |
| Colao et al. [19] | 182 | R, P, DB | 12 mo | TSS (n = 80); RT (n = 1); de novo (n = 101) |
Pts not selected for prior response | Optional uptitration in pts with mean GH ≥2.5 μg/L and/or IGF-1 > ULN at 3 and 7 mo | GH > 1 μg/L after OGTT or mean GH > 5 µg/L and IGF-1 > ULN for age and sex | GH < 2.5 µg/L IGF-1 normal |
94 (52) | 43 (24) | 35 (19) |
CO crossover, DA dopamine agonist, DB double blind, GH growth hormone, IGF-1 insulin-like growth factor 1, lan lanreotide, LAR long-acting release, mo month, oct octreotide, OGTT oral glucose tolerance test, OL open label, P prospective, pts patients, R randomized, Ret retrospective, RT radiotherapy, sc subcutaneous, SR slow release, SSA somatostatin analogues, TSS transsphenoidal surgery, ULN upper limit of normal, wk week, yr year, Y yttrium
aGH < 2 µg/L
bIGF-1 to within normal range
cGH < 5 mU/L
dIGF-1 < 65 nmol/L
eResponse at last follow-up
fOnly patients who completed 48 weeks of treatment in the Lancranjan et al. study [9] and had diagnostic GH (n = 91) or IGF-1 (n = 67) data were considered for this retrospective analysis