Background
Methods
Search methodology
Data extraction
Results
Search results
Study characteristics
Clinical trial | Yr | Country | Sites | Study type Treatment years | Treatments/arms | ND HGG (n) | Gliadel wafer plus RT/TMZ (n) | GBM (n) | Other HGG (n) |
---|---|---|---|---|---|---|---|---|---|
Aoki et al. [27] | 2014 | Japan | 10 | Phase I/II study 2009 to 2012 | Resection + Gliadel wafer + RT/TMZ | 16 | 16 | 9 | 7 |
Bock et al. [28] | 2010 | Germany | 7 | Retrospective analysis for safety risks 2005 to 2008 | Resection + Gliadel wafer + RT/TMZ | 44 | 44 | 44 | 0 |
Burri et al. [29] | 2015 | USA | 4 | Phase II/2003 to 2008 | Resection + Gliadel wafer + early TMZ (day 4) + RT/TMZ | 46 | 46 | 43 | 3 |
Duntze et al. [30] | 2012 | France | 17 | Prospective, observational 2007 to 2009 | Resection + Gliadel wafer + RT/TMZ | 92 | 65 | 74 | 18 |
McGirt et al. [31] | 2009 | USA | 1 | Retrospective analysis 1997 to 2006 | (1) Resection + Gliadel wafer + RT/TMZ | 33 | 33 | 33 | 0 |
(2) Resection + Gliadel wafer + RT | 78 | 78 | 0 | ||||||
(3) Resection/biopsy + RT/TMZ | 45 | 45 | 0 | ||||||
Menei et al. [32] | 2010 | France | 26 | Retrospective analysis 2005 to 2006 | (1) Resection + Gliadel wafer + RT/TMZ | 43 | 43 | 72 | 11 |
(2) Resection + Gliadel wafer + other regimens | 40 | ||||||||
Miglierini et al. [33] | 2012 | France | 1 | Retrospective analysis 2006 to 2010 | Resection + Gliadel wafer + RT/TMZ | 24 | 22 | 16 | 8 |
Noel et al. [34] | 2012 | France | 1 | Retrospective analysis 2007 to 2008 | (1) Resection + Gliadel wafer + RT/TMZ | 28 | 28 | 20 | 8 |
(2) Resection/biopsy + RT/TMZ | 37 | 16 | 21 | ||||||
Pan et al. [35] | 2008 | USA | 1 | Retrospective analysis 2003 to 2005 | Resection + Gliadel wafer + RT/TMZ | 21 | 21 | 21 | 0 |
Pavlov et al. [36] | 2015 | France | 1 | Retrospective analysis 2004 to 2012 | Resection + Gliadel wafer + RT/TMZ | 83 | 61 | 83 | 0 |
Salvati et al. [37] | 2011 | Rome | 1 | Retrospective analysis 2006 to 2008 | Resection + Gliadel wafer + RT/TMZ | 32 | 32 | NA | NA |
Patient characteristics
Clinical trial | Treatments/arms | ND HGG (n) | Gliadel wafer plus RT/TMZ (n) | Mean age (range) | % male | KPS score | EOR | MGMT status | # Gliadel wafers |
---|---|---|---|---|---|---|---|---|---|
Aoki et al. [27] | Resection + Gliadel wafer + RT/TMZ | 16 | 16 | 50 (21–63) | 50.0 % | 87.5 % >80 | Mean 91.9 % | No | ≤8 |
Bock et al. [28] | Resection + Gliadel wafer + RT/TMZ | 44 | 44 | 57 (28–74) | 63.6 % | 81 ± 15.3 | 86 % total | No | 7.3 ± 1.3 |
Burri et al. [29] | Resection + Gliadel wafer + early TMZ (day 4) + RT/TMZ | 46 | 46 | 56 (19–73) | 60.9 % | 80 | 70 % total | Yes, performed on 22 pts | 8 |
Duntze et al. [30] | Resection + Gliadel wafer + RT/TMZ | 92 | 65 | 58 (34–76) | 69.6 % | Median 80 | 86 % >90 % | No | 6.5 |
McGirt et al. [31] | (1) Resection + Gliadel wafer + RT/TMZ | 33 | 33 | 57 (50–81) | 60.0 % | 80 | 77 % total | No | 8 |
(2) Resection + Gliadel wafer + RT | 78 | NA | NA | ||||||
(3) Resection/biopsy + RT/TMZ | 45 | (18–70) | NA | ||||||
Menei et al. [32] | (1) Resection + Gliadel wafer + RT/TMZ | 43 | 43 | 60 (18–80) | 58.1 % | Median 80 | 84.3 % >90 % | No | 8 |
(2) Resection + Gliadel wafer + other regimens | 40 | ||||||||
Miglierini et al. [33] | Resection + Gliadel wafer + RT/TMZ | 24 | 22 | Mean 60.25 Median 63 5 pts >70 | 70.8 % | 75 % PS 0–1 | 50 % total | No | 8 |
Noel et al. [34] | (1) Resection + Gliadel wafer + RT/TMZ | 28 | 28 | 61 (17–82) | 53.6 % | 92.8 % ≥80 | 35.7 % total | Yes | 8 |
(2) Resection/biopsy + RT/TMZ | 37 | 61 (17–82) | 40.5 % | 81.1 % ≥80 | 24.3 % total | ||||
Pan et al. [35] | Resection + Gliadel wafer + RT/TMZ | 21 | 21 | 60 (48–83) | 66.7 % | Median 80 | 67 % total | No | 8 |
Pavlov et al. [36] | Resection + Gliadel wafer + RT/TMZ | 83 | 61 | 59.9 (21–78) | 60.2 % | 94 % ≥70 | 49.1 % total | No | 7.1 (3–13) |
Salvati et al. [37] | Resection + Gliadel wafer + RT/TMZ | 32 | 32 | Median 58.5 (35–72) | 50.0 % | Mean 80.6 | 100 % total | No | 8 (5–10) |
Efficacy results
Median overall survival
Clinical trial | Treatments/arms | ND HGG (n) | Gliadel wafer plus RT/TMZ (n) | Median OS (months) | OS, 1 year (%) | OS, 2 years (%) | Median PFS (months) | PFS, 6 months (%) | PFS, 1 year (%) |
---|---|---|---|---|---|---|---|---|---|
Aoki et al. [27] | Resection + Gliadel wafer + RT/TMZ | 16 | 16 | 20.2a
| 100.0 % | 68.8 %, 44.4%a
| NA | 75.0 % | 62.5 % |
Bock et al. [28] | Resection + Gliadel wafer + RT/TMZ | 44 | 44 | 12.7 | 58.0 % | 13.0 % | 7 | 63.0 % | 35.0 % |
Burri et al. [29] | Resection + Gliadel wafer + early TMZ (day 4) + RT/TMZ | 46 | 46 | 18 | 76.0 % | 33.0 % | 8.5 | 72.0 % | 33.0 % |
Duntze et al. [30] | Resection + Gliadel wafer + RT/TMZ | 92 | 65 | 18.8 | 70.0 % | 37.0 % | 10.5 | 74 % | 41.0 % |
McGirt et al. [31] | (1) Resection + Gliadel wafer + RT/TMZ | 33 | 33 | 21.3 | NA | 36.0 % | NA | 93.0 % | NA |
(2) Resection + Gliadel wafer + RT | 78 | 12.4b
| NA | NA | NA | NA | NA | ||
(3) Resection/biopsy + RT/TMZ | 45 | 14.7c
| NA | NA | NA | NA | NA | ||
Menei et al. [32] | (1) Resection + Gliadel wafer + RT/TMZ | 43 | 43 | 17 | NA | NA | NA | NA | NA |
(2) Resection + Gliadel wafer + other regimens | 40 | NA | NA | NA | NA | NA | NA | ||
Miglierini et al. [33] | Resection + Gliadel wafer + RT/TMZ | 24 | 22 | 19.2 | 78.0 % | 24.0 % | 12.3 | 81.50 % | 52.0 % |
Noel et al. [34] | (1) Resection + Gliadel wafer + RT/TMZ | 28 | 28 | 20.6 | 78.6 % | 40.9 % | 12.9 | NA | 52.0 % |
(2) Resection/biopsy + RT/TMZ | 37 | 20.8 | 78.4%d
| 33.3 % | 14 | NA | 55.0%e
| ||
Pan et al. [35] | Resection + Gliadel wafer + RT/TMZ | 21 | 21 | 17 | NA | 39.0 % | 8.5 | 71.0 % | NA |
Pavlov et al. [36] | Resection + Gliadel wafer + RT/TMZ | 83 | 61 | 19.5 | NA | NA | 8.5 | NA | NA |
Salvati et al. [37] | Resection + Gliadel wafer + RT/TMZ | 32 | 32 | NA | 100 % | NA | NA | 100 % | NA |
Overall 1- and 2-year survival rates
Progression-free survival
Subgroup analyses and prognostic factors
Safety results
Clinical trial | Number | CE | HA | IH | II | ND | S | LE | F | GI | MY | SK | TE | Total, n
|
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aoki et al. [27]a
| 24 | 2 | 5 | 1 | 2 | 1 | 4 | 15 | ||||||
Bock et al. [28] | 44 | 7 | 11 | 6 | 8 | 7 | 1 | 6 | 46 | |||||
Burri et al. [29] | 46 | 1 | 2 | 7 | 3 | 3 | 3 | 18 | 2 | 39 | ||||
Duntze et al. [30]b
| 92 | 3 | 2 | 5 | 12 | 7 | 29 | |||||||
Miglierini et al. [33] | 24 | 3 | 3 | 6 | ||||||||||
Noel et al. [34] | 28 | 4 | 4 | |||||||||||
Pan et al. [35] | 21 | 1 | 1 | 2 | ||||||||||
Pavlov et al. [36] | 61 | 2 | 3 | 1 | 6 | |||||||||
Salvati et al. [37] | 32 | 2 | 0 | |||||||||||
Total, n
| 372 | 10 | 16 | 11 | 18 | 29 | 11 | 5 | 1 | 1 | 38 | 1 | 8 | 147 |
Total, % | 2.7 % | 4.3 % | 3.0 % | 4.8 % | 7.8 % | 3.0 % | 1.3 % | 0.3 % | 0.3 % | 10.2 % | 0.2 % | 2.15 % | 39.5 % |
Discussion
Efficacy of Gliadel plus RT/TMZ
Safety review
Clinical trial | Number | CE | HA | IH | II | ND | S | LE | F | GI | MY | SK | TE | UI |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Grade 3 and 4 AEs, 9 Gliadel wafers + RT/TMZ, % | 372 | 2.7 % | 4.3 % | 3.0 % | 4.8 % | 7.8 % | 3.0 % | 1.3 % | 0.3 % | 0.3 % | 10.2 % | 0.2 % | 2.15 % | |
287 | 7.0 % | 13.0 % | 2.0 % | 16.0 % | 3.0 % | 6.0 % | ||||||||
120 | 23.0 % | 16.0 % | 9.0 % | 5.0 % | 16.0 % | 33.0 % | 27.0 % | 700 % | 18.0 % | |||||
120 | 19.0 % | 12.0 % | 2.0 % | 6.0 % | 10.0 % | 38.0 % | 15.0 % | 47.0 % | 17.0 % | |||||
AEs, Attenello et al., [46] Gliadel wafer arm, % | 288 | 2.3 % | 2.8 % | 1.2 % | 14.6 % | 0.3 % | 11.2 % | |||||||
AEs, Attenello et al., [46] placebo arm, % | 725 | 2.1 % | 2.2 % | 0.7 % | 15.7 % | 0.3 % | 8.9 % |