Phase 1 trial of O<sup>6</sup>‐benzylguanine and BCNU in children with CNS tumors: A Children's Oncology Group study
Bibliographic record
Abstract
BACKGROUND: Efficacy of nitrosoureas is limited by host repair of drug-induced alkylation. O(6)-benzylguanine (O(6)-BG), an inhibitor of host alkylation repair, and BCNU were studied in children with refractory/untreatable central nervous system tumors to determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of BCNU administered following O(6)-BG. PROCEDURE: O(6)-BG (120 mg/m(2) IV over 1 hr) was followed by BCNU (IV over 1 hr). Cohorts of three to six patients were treated with escalating doses of BCNU. Courses were repeated every 6 weeks. Patients in Stage 1 were accrued irrespective of prior treatment. Once the MTD was exceeded, Stage II accrual was limited to less heavily pretreated patients (</= two prior chemotherapy regimens, no prior central axis radiation, no prior bone marrow transplant, and no bone marrow involvement). RESULTS: Twelve patients in Stage I and 13 in Stage II (less heavily pretreated patients only) were evaluable for toxicity. The MTD of BCNU administered with O(6)-BG (120 mg/m(2) IV) was 58 mg/m(2) in less-heavily pretreated patients. Myelosuppression, which was cumulative in some patients receiving multiple cycles of therapy, was the predominate DLT. Twenty-four patients were evaluable for response: after two courses of therapy, 6 had stable disease, 17 had progressive disease, and 1 patient had a minor response but progressed after four courses of therapy. CONCLUSIONS: Based on lack of activity of this combination in adult phase II studies, no further testing of O(6)-BG plus BCNU in children is planned. Strategies to decrease hematopoeitic toxicity of BCNU plus O(6)-BG are required.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".