Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Temozolomide · 9 trials · 12 indications
Overall Survival was defined as the time from the date of randomization to the date of death from any cause.
Complete Response (CR): \< 5% blasts in normocellular bone marrow (BM); Absolute Neutrophil Count (ANC) \> 1.0 x 10\^9/L, platelets \> 100 x 10\^9/L, and no extramedullary disease. CR with incomplete platelet recovery (CRp): All the criteria of CR but with platelets \< 100 x 10\^9/L but ≥ 50 x 10\^9/L and platelet transfusion independent. Morphologic leukemia-free state (MLFS): complete clearance of blasts from marrow and blood, but criteria for CR or CRp not met. Partial response (PR): decrease ≥ 50% BM blasts. Minimal Response (MR): decrease ≥ 25% but \<50% BM blasts.
An experimental assay was developed to measure MGMT levels.
Progression-free survival as determined by Kaplan-Meier method.
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy. Adverse events were classified under the system organ class using MedDRA-J Version 11.0.
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy.
Safety was assessed from the start of administration during the concomitant radiotherapy phase until 30 days after the completion of administration of monotherapy.
| Arm | Type | Description |
|---|---|---|
| Temodal group | EXPERIMENTAL | Subjects treated with temozolomide. |
| Semustine group | ACTIVE_COMPARATOR | Subjects treated with semustine. |
| A | EXPERIMENTAL | temozolomide 150 mg/m2/day PO, on 7 consecutive days every 14 days ("7 days on / 7 days off" continuously) |
| B | ACTIVE_COMPARATOR | dacarbazine 1000 mg/m2 IV, on Day 1 +/- 3 days every 3 weeks |
| Temozolomide | EXPERIMENTAL | Temozolomide capsules orally, once daily: 1 induction cycle (200 mg/m\^2/day for 7 days in 1 28 day cycle), 1 consolidation cycle (200 mg/m\^2/day for 7 days in 1 28 day cycle), then 200 mg/m\^2/day for 7 days each 28-day cycle or for 5 days each 28-day cycle (12 cycle maximum). Alternatively participants could have received 100 mg/m\^2/day for 21 days of each 28-day cycle (12 cycle maximum). |
| Temozolomide treatment | EXPERIMENTAL | - |
| No treatment | NO_INTERVENTION | - |
| Single arm | EXPERIMENTAL | It is the only arm of the study. Subjects receive a combination of radiotherapy and temozolomide, and then temozolomide monotherapy. |
| Subjects with melanoma | EXPERIMENTAL | - |
| Subjects with breast cancer | EXPERIMENTAL | - |
| Subjects with non-small cell lung cancer | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Temozolomide | DRUG | Temozolomide orally for 5 consecutive days (Day 1 through Day 5) every 28 days, at a dose of 150 mg/m2/day for subjects previously treated with chemotherapy, or 200 mg/m2/day for subjects who have not received previous chemotherapy. |
| Semustine | DRUG | Semustine orally once every 28 days at a dose of 150 mg/m2/day. |
| Dacarbazine | DRUG | intravenous solution; dacarbazine 1000 mg/m2 IV (in the vein), on Day 1 +/- 3 days every 3 weeks; one cycle of dacarbazine is defined as a 3-week period; treatment will continue until progression of the disease, unacceptable toxicity, subject refusal, or opinion of the treating physician that it is in the subject's best interest to stop. |
| Radiotherapy | RADIATION | Radiotherapy will be administered in combination with temozolomide during the concomitant radiotherapy phase. Radiotherapy will consist of a conventionally fractioned regimen, delivering a total dose of 60 Gy in 6 weeks, in a once daily schedule of 2 Gy per fraction, for a total of 30 fractions. Radiation will be provided by a linear accelerator of x ray energy of 4 MV or higher. |
Inclusion Criteria: * Prior histologic confirmation of glioblastoma, anaplastic astrocytoma. * Evidence of tumor progression or recurrence. * Age \>=18 years. * Karnofsky performance status \>=60%. * Absolute neutrophil count \>=1,500/mm\^3, platelet count \>=100,000/mm\^3, hemoglobin \>=8g/dL. * S...