Safety and efficacy of presurgical neoadjuvant low-dose temozolomide in glioma patients.
Bibliographic record
Abstract
e12510^ Background: Temozolomide (TMZ) has become the chemotherapy of choice for patients with malignant glioma. Activity has been demonstrated in a range of tumor histologies and tumor grades. A possible mechanism of resistance is the presence of high methylguanine methyltransferase (MGMT) in the tumor leading to reduced cytotoxic activity of TMZ. Experimental models have shown that continuous exposure to TMZ can deplete MGMT activity and possibly restore sensitivity to TMZ. Presurgical (neoadjuvant) treatment with TMZ may be beneficial in reducing MGMT activity and improving patient outcome. Methods: This phase II study assessed the safety and efficacy of TMZ at a dose of 75 mg/m2 administered daily for 14 days prior to surgery for treatment-naïve glioma. Results: 40 patients, median age 47 (18-76) with surgically resectable tumors were enrolled from December 2006 to December 2009. Ninteen male and 21 female patients self-selected to TMZ (34) or control (6) cohorts. Tumors were: oligodendrogliomas 37%, astrocytomas 28%, glioblastoma multiforme 18% and Mixed tumors 17%; 50% were high grade tumors. A majority of patients 63% had a partial resection; the remaining had a complete resection. MGMT promoter methylation was performed on fresh frozen tissue and significant levels were found in 60% of patients. All patients in the TMZ cohort completed 2 weeks of therapy. Treatment was well tolerated and toxicities were rare with 60% of patients not reporting any treatment related adverse events. Lymphopenia was the only grade 3 toxicity observed in TMZ treated patients. No grade 4 toxicities were reported. At histological examination, an increased number of apoptotic cells were observed in tumor from TMZ patients. Conclusions: Presurgical neoadjuvant TMZ is well tolerated with few toxicities observed. The increased number of apoptotic cells demonstrated action of TMZ on the tumors and suggest tumor cytoreduction could be performed before surgery. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Canada/Merck Schering-Plough Canada/Merck Merck Schering-Plough Canada/Merck Schering-Plough Canada/Merck In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.
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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 | 0.001 |
| 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".