ArticleTargeted oncology2016
Dose-Dense Temozolomide in Patients with MGMT-Silenced Chemorefractory Colorectal Cancer.
Article in Targeted oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
NIVOLUMAB Plus IPILIMUMAB and TEMOZOLOMIDE in Combination in Microsatellite Stable (MSS), MGMT Silenced Metastatic Colorectal Cancer (mCRC): the MAYA Study
Phase 1b/2 Trial of 5-fluorouracil, Leucovorin, Irinotecan in Combination With Temozolomide (FLIRT) and Bevacizumab for the First-line Treatment of Patients With MGMT Silenced, Microsatellite Stable Metastatic Colorectal Cancer.
Temozolomide and Irinotecan Consolidation in Patients With MGMT Silenced, Microsatellite Stable Colorectal Cancer With Persistence of Minimal Residual Disease in Liquid Biopsy After Standard Adjuvant Chemotherapy: the ERASE-TMZ Study
Multicenter Phase II Study of Preoperative Chemoradiotherapy With CApecitabine Plus Temozolomide in Patients With MGMT Silenced and Microsatellite Stable Locally Advanced RecTal Cancer: the CATARTIC Trial
Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Temozolomide Followed by Combination With Low-Dose Ipilimumab and Nivolumab in Patients With Microsatellite-Stable, OJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- A phase 2 study of temozolomide in pretreated metastatic colorectal cancer with MGMT promoter methylation.British journal of cancer · 2017Trial
- Spatial predictors of response to chemo-immunotherapy in microsatellite stable metastatic colorectal cancer.Nature communications · 2026Article
- Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer.Clinical and translational radiation oncology · 2023Article
- Temozolomide combined with ipilimumab plus nivolumab enhances T cell killing of MGMT-expressing, MSS colorectal cancer cells.American journal of cancer research · 2023Article
- MGMT inactivation as a new biomarker in patients with advanced biliary tract cancers.Molecular oncology · 2022Article
- Article
- Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications.Current neuropharmacology · 2021Review
- Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors.Cancer research · 2019Article
- Constitutional mismatch repair-deficiency: current problems and emerging therapeutic strategies.Oncotarget · 2018Review
- Trifluridine/Tipiracil (TAS-102) in Refractory Metastatic Colorectal Cancer: A Multicenter Register in the Frame of the Italian Compassionate Use Program.The oncologist · 2018Article
- High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine.Familial cancer · 2016Review
- MGMT function determines the differential response of ATR inhibitors with DNA-damaging agents in glioma stem cells for GBM therapy.Neuro-oncology advancesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn a phase II study, we showed that temozolomide (TMZ) was tolerable and active in heavily pre-treated patients with advanced colorectal cancer (CRC) and MGMT methylation. A schedule of dose-dense TMZ may have enhanced activity due to the higher cumulative dose and induction of MGMT depletion, even in resistant tumors.
methodsThirty-two patients with chemorefractory MGMT-methylated CRC were treated with TMZ at a daily dose of 75 mg/m(2) for 21 consecutive days every 4 weeks, for up to six cycles or until the occurrence of progressive disease/unacceptable toxicity. The primary endpoint was treatment activity in terms of objective response rate (ORR). MGMT protein expression was tested by immunohistochemistry (IHC) on two pooled cohorts: patients from the previous study of standard-dose TMZ and those from the current investigation.
resultsFrom November 2013 to December 2014, 32 patients were treated at Fondazione IRCCS Istituto Nazionale dei Tumori. We observed only three episodes of grade 3 asthenia and no significant myelotoxicity. The ORR was 16 % (all partial responses occurring in RAS-BRAF-mutated tumors). Median progression-free survival (PFS) and overall survival (OS) were 2.3 and 6.7 months, respectively. Patients with MGMT-low expression by IHC had a significantly higher ORR (p < 0.0001) and PFS (p = 0.001) compared to those with MGMT-high expression, while no difference was observed in OS.
conclusionsOur data confirm the encouraging activity of TMZ in chemorefractory CRC patients selected for MGMT silencing, even in the RAS-BRAF-mutated population. The role of MGMT IHC as a biomarker for improving patient selection warrants further prospective confirmation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.