Combination procarbazine and temozolomide for temozolomide-resistant adult gliomas
Bibliographic record
Abstract
11503 Background: As Temozolomide has become incorporated in the first line treatment of glioblastoma multiforme as well as the salvage therapy of many low-grade gliomas, we are increasingly faced with Temozolomide failures. There is currently no standard second-line chemotherapy for Temozolomide-resistant tumors. In what is usually a palliative setting, toxicity and convenience are important considerations in the choice of a second-line regimen. Methods: We reviewed our experience with a combination oral regimen for Temozolomide failure. The regimen consisted of a 28-day cycle with Procarbazine given at 100–150mg/m2/d on days 1–5, and Temozolomide at 150mg/m2/d on days 1–5. This was initiated at the time of radiological and/or clinical progression while on Temozolomide, and continued until further progression or toxicity was documented. Results: 12 patients, median age 52 (range 38–68), were treated with concomitant Procarbazine and Temozolomide at our institution since November 2004. All patients had histologically confirmed gliomas (glioblastoma multiforme (10), grade II oligodendroglioma (1), grade II oligoastrocytoma (1)), and all had undergone prior maximal safe resection and external beam radiotherapy. All patients were receiving Temozolomide, either in the adjuvant setting (after concurrent chemo-radiotherapy in 6 of 12), or as salvage monotherapy for recurrence. No patient met the RECIST criteria for PR. Patients progressed after a median of 2 cycles (range: 1–10) but the 6-month actuarial progression-free survival was 40% (80% of patients with SD had glioblastoma multiforme). No Grade 3 or 4 toxicity was seen. No patient discontinued treatment because of toxicity. The Procarbazine dose was prophylactically reduced (75mg/m2/d) in one patient with poor hematological tolerance to prior chemotherapy. Conclusions: The combination of Procarbazine and Temozolomide given in a 28-day cycle is a well-tolerated oral second-line regimen for glioma patients failing Temozolomide. The activity of this regimen is modest but prolonged progression-free survival can be seen. [Table: see text]
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".