Table 5.
Temozolomide-containing combination trials for recurrent or progressive glioblastomaa
| Reference | Study Design/Population | TMZ Pretreatment | Regimen | n | Radiographic Response (%) | PFS6* (%) | mPFS* (mo) | mOS* (mo) | WHO Grades 3/4 Toxicities (n) |
|---|---|---|---|---|---|---|---|---|---|
| Temozolomide + Bevacizumab Combinations | |||||||||
| Desjardins et al.85 | Phase II. Median age: 56 y; 1st progression: n = 15; 2nd progression: n = 15; 3rd progression: n = 2 |
Yes (prior BEV 4 pts) | TMZ 50 mg/m2/d + BEV 10 mg/kg i.v. q2wk | 32 |
CR: 0 PR: 9 SD: 16 PD: 7 |
18.8 | 3.7 | 8.7 |
Hematologic:0 Nonhematologic: 11 (including 1 grade 5 infection) |
| Verhoeff et al.70 | Phase Median age: 55 y | Yes | TMZ 50 mg/m2/d q3wk + BEV 10 mg/kg i.v. q3wk | 15 | NA | 6.7 | 2.4 | 3.7 | NA |
| Temozolomide + Nitrosourea Combinations | |||||||||
| Gaviani et al.73 | Noncomparative, single-arm | Yes | TMZ 150 mg/m2 on days 1–7 and 15–21 of 28-d cycles + FOT single i.v. infusion 110 mg/m2 monthly on day 15 | 20 (only 10 evaluable) | NA | 40 | 4.3 | NA |
Hematologic: Severe Nonhematologic: NA |
| Temozolomide + Interferon Combinations | |||||||||
| Groves et al.74 | Two phase II noncomparative studies. Short-acting IFN: median age: 55 y; median KPS: 80. PEG-IFN: Median age: 56 y; median KPS: 90 |
No | TMZ 150–200 mg/m2/d for 5 days every month + short-acting IFN-α2b: 4 MU/m2 s.c. 3×/wk and TMZ 150–200 mg/m2/d × 5 days every month + long-acting PEG-IFN-α2b s.c. 0.5 µg/kg/wk |
29 26 |
CR: 0 PR: 4 SD: 18 CR: 0 PR: 1 SD: 17 |
31 38 |
3.6 4.4 |
7.2 10.0 |
Hematologic: 18 Nonhematologic: 10 Hematologic: 17 Nonhematologic: 23 |
| Temozolomide + Miscellaneous Chemotherapy Combinations | |||||||||
| Reardon et al.75 | Phase II. single-arm; Median age: 53.6 y; |
Yes | TMZ continuous daily 50 mg/m²/d + sorafenib 400 mg 2×/d | 32 |
CR: 0 PR: 1 SD: 15 PD: 16 |
9.4 | 1.5 | 9.7 |
Hematologic: 1 Nonhematologic: 27 |
| Eisenstat et al.82 | Phase II. median age: 58 y; 1st recurrence: 100% |
Yes (prior chemoradiotherapy) | TMZ 75 mg/m2 for 21 d per 28-d cycle + afatinib 40 mg/d or afatinib 40 mg/d or TMZ 75 mg/m2 for 21 d per 28-d cycle |
39 41 39 |
CR: 1 PR: 2 SD: 14 PD: 17 CR: 0 PR: 1 SD: 14 PD: 23 CR: 0 PR: 4 SD: 21 PD: 13 |
10 3 23 |
1.5 1.0 1.9 |
NA |
Hematologic: 0 Nonhematologic: 11 Hematologic: 5 Nonhematologic: 10 Hematologic: 3 Nonhematologic: 17 |
| Quinn et al.83 | Phase II, open-label | Yes | TMZ 472 mg/m2 p.o. on day 1 of 28-d cycle + O6-BG 1-h infusion of 120 mg/m2, followed immediately by a 48-h infusion of 30 mg/m2 on day 1 of 28-d cycle | 34 |
CR: 0 or 1 PR: 0 or 1 SD: NA PD: NA |
9 | 1.8 | 4.5 | NAb |
| Stockhammer et al.84 | Retrospective analysis. 1st recurrence: n = 24; 2nd recurrence: n = 4 |
Yes (except 4 pts) | TMZ 10 mg/m2 b.i.d. + CEL 200 mg/d | 28 |
CR: 0 PR: 3 SD: 15 PD: 10 |
43 | 4.2 | 16.8 |
Hematologic: 1 Nonhematologic: NA |
| Boiardi et al.76 | Nonrandomized, retrospective | No | TMZ 200 mg/m2 days 1–5 every 28 days + resection + mitoxantrone, delivered through Rickam reservoir (4 mg/d on days 1–5 q28d) or TMZ + resection or TMZ 200 mg/m2 days 1–5 q28d alone |
65 50 161 |
NA | 70.7 64 39.3 |
NA | 11 8 5 |
NA |
| Reardon et al.77 | Phase I | No | TMZ 200 mg/m2/d days 1–5 + CPT-11 40 mg/m2 to 375 mg/m2 i.v. on weeks 1, 2, 4, and 5 of each 6-wk cycle | 91 | NAb | 27.3 | 12.8 | NAb | NAb |
| Chua et al.78 | Phase II, open-label. Median age: 55 y; 1st relapse |
No (prior chemotherapy: 9%) | TMZ 200 mg/m2 p.o. on days 1–5 q4wk + liposomal DOX 40 mg/m2 i.v. on day 1 q4wk | 22 |
CR: 1 PR: 3 SD: 11 PD: 7 |
32 | 3.6 | 8.2 |
Hematologic: 8 Nonhematologic: 9 |
| Silvani et al.79 | Phase II, single-center. Median time from 1st diagnosis: 8 mo |
No | TMZ 200 mg/m2 on days 2–6 q4wk + CIS 40 mg/m2, on days 1 and 2 q4wk | 20 |
CR: 0 PR: 2 SD: NA PD: NA |
35 | NA | NAb | NAb |
| Brandes et al.80 | Phase II, multicenter. median age: 53.4 y; Median KPS: 80 |
No (chemotherapy-naive) | TMZ 130 mg/m2 bolus followed by 9 doses of 70 mg/m2 q12h (total of 5 d) from day 2 q4wk (if no hematologic toxicity dose, increased to 100 mg/m2) + CIS 75 mg/m2 on day 1 q4wk | 50 |
CR: 1 PR: 9 SD: NA PD: NA |
34 | 4.3 | 11.2 |
Hematologic: 13 Nonhematologic: 4 |
Abbreviations: BEV, bevacizumab; CEL, celecoxib; CIS, cisplatin; CPT-11, irinotecan; CR, complete response; DOX, doxorubicin; FOT, fotemustine; IFN, interferon; KPS, Karnofsky performance score; mOS, median overall survival; mPFS, median progression-free survival; NA, not available; O6-BG, O6-benzylguanine; PD, progressive disease; PEG-IFN, PEGylated interferon; PFS6, 6-month PFS rate; PR, partial response; SD, stable disease.
For the most part, only glioblastoma data are presented in the table. We have reported enrollment numbers for different patient populations only when all data in a paper are presented for combined patient populations.
*Disease PFS and OS were calculated from beginning of retreatment with TMZ.
aData are presented for glioblastoma patients only.
bData are not available because not presented separately for glioblastoma and other glioma patients.