Table 1.
Phase II trials of standard and dose dense temozolomide administration schedules for recurrent malignant gliomas
| Study | Dose mg/m2 | Dose intensity mg/m2/week | Schedule | Tumor type | No. of patients | RR % | 6PFS % | OS months | Grade 3–4 hematological toxicity (no. of patients) | Grade 3–4 nonhematological toxicity (no. of patients) |
|---|---|---|---|---|---|---|---|---|---|---|
| Standard treatment | ||||||||||
| Yung et al8 | 150–200 | 250 | 5/28 | AA | 111 | 35 | 46 | 5.4 | 1 anemia | 16 nausea |
| 3 neutropenia | 10 vomiting | |||||||||
| 3 leukopenia | 10 headache | |||||||||
| 10 thrombocytopenia | 9 asthenia | |||||||||
| 7 fatigue | ||||||||||
| Yung et al9 | 150–200 | 250 | 5/28 | GBM | 112 | 5.3 | 21 | 2.9 | 1 anemia | 3 nausea |
| 4 neutropenia | 3 vomiting | |||||||||
| 1 leukopenia | 2 headache | |||||||||
| 8 thrombocytopenia | 1 constipation | |||||||||
| 3 fatigue | ||||||||||
| Dose-dense dosing schedules | ||||||||||
| Wick et al28 | 150 | 525 | 7/14 | GBM | 39 | 5.1 | 43 | – | 1 grade 4 anemia | 2 nausea |
| 3 neutropenia | 4 fatigue | |||||||||
| 1 febrile neutropenia | ||||||||||
| 6 thrombocytopenia | ||||||||||
| Tosoni et al29 | 75 | 400 | 21/28 | GBM | 51 | – | – | – | 52% of patients any grade lymphocytopenia 1 grade 5 hematological toxicity |
1 herpes zoster concomitant with grade 2 lymphocytopenia 3 infections concomitant with grade 3 lymphocytopenia 1 fungal penumonia concomitant with grade 4 lymphocytopenia 1 grade 5 infection concomitant with grade 4 pancytopenia 1 grade 5 pulmonary thromboembolism |
| Chinot et al30 | 150 | 525 | 7/17 | GBM | 29 | 24 | – | 6,1 | 6 thrombocytopenia | 3 grade 3 febrile neumonitis with lymphocytopenia |
| 6 lymphocytopenia | ||||||||||
| 5 neutropenia | 2 grade 3 febrile neumonitis with neutropenia | |||||||||
| 5 leukopenia | ||||||||||
| 1 grade 3 febrile neutropenia | 1 grade 4 pulmonary embolism | |||||||||
| 2 grade 3 infection whitout neutropenia | ||||||||||
| 1 grade 3 constipation | ||||||||||
| 1 grade 3 asthenia | ||||||||||
| Wick et al31 | 150 | 525 | 7/14 | GBM, LGGs, AA, AOA, Other | 64 | 15 | 43,8 | – | 1.2% of patients neutropenia | – |
| 1.8% of patients lymphocytopenia | ||||||||||
| 10.4% of patients thrombocytopenia | ||||||||||
| Neyns et al32 | 100 | 525 | 21/28 | AA | 15 | 13 | 56 | 12,9 | 53% of patients lymphocytopenia | 1 herpes zoster concomitant with grade 3 lymphocytopenia |
| 47% of patients lymphocytopenia | 1 grade 5 P. carinii pneumonia concomitant with grade 4 lymphocytopenia | |||||||||
| Perry et al36 | 50 | 350 | 28/28 | GBM | 21 | – | 17 | – | lymphocytopenia | |
| GBM | 14 | – | 57 | – | ||||||
| AA | 14 | – | 42 | – | ||||||
| Berrocal et al33 | 85 | 446 | 21/28 | AA and GBM | 39 | 5.1 | 20 | 5.9 | 7% of patients thrombocytopenia | – |
| 3.5% of patients neutropenia | ||||||||||
Abbreviations: AA, anaplastic astrocytoma; AOA, anaplastic oligoastrocytomas; GBM, glioblastoma multiforme; LGG, low-grade gliomas; other, meningioma, ependimoma, sarcoma; OS, overall survival; 6PFS, progression-free survival at 6 months; RR, respone rate.