Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer

Jeong, Jae Ho; Hong, Yong Sang; Park, Yangsoon; Kim, Jihun; Kim, Jeong Eun; Kim, Kyu-Pyo; Kim, Sun Young; Park, Jin‐Hong; Kim, Jong Hoon; Park, In Ja; Lim, Seok‐Byung; Yu, Chang Sik; Kim, Jin Cheon; Kim, Tae Won

doi:10.1016/j.ijrobp.2016.05.009

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…Pathologic complete response was observed in 37.5% and 16.7% of the hypermethylated and unmethylated MGMT groups, respectively (P = 0.616). To this author’s knowledge, there have not been subsequent published studies building off these results [38] .…”

Section: Discussionmentioning

confidence: 86%

Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer

Jensen

Pourfarrokh²,

Volz³

et al. 2023

Clinical and Translational Radiation Oncology

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Section: Discussionmentioning

confidence: 86%

Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer

Jensen

Pourfarrokh²,

Volz³

et al. 2023

Clinical and Translational Radiation Oncology

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“…Sinha et al (10) observed that MGMT methylation was associated with stage III in sporadic colorectal cancer cases. Recently, the methylation status of MGMT has been correlated with pathologic complete response in colorectal cancer patients (11).…”

Section: Discussionmentioning

confidence: 99%

MGMT Promoter Methylation in Patients with Rectal Adenocarcinoma After Chemoradiotherapy Treatment: Clinical Implications

et al. 2019

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Aims: To analyze the clinical relevance of O6-methylguanine-DNA methyltransferase in rectal adenocarcinoma treated with chemoradiotherapy followed by surgery. Methods: Tissue samples from 29 rectal adenocarcinoma patients were obtained after chemoradiotherapy. O6-methylguanine-DNA methyltransferase promoter methylation status was established by methylation-specific polymerase chain reaction. O6-methylguanine-DNA methyltransferase protein levels were determined by immunohistochemistry. Clinicopathologic variables, including treatment regression grade, recurrence, lymph node invasion, and stage and differentiation grade of the tumor, were determined. Results: The O6-methylguanine-DNA methyltransferase gene promoter was methylated in 81.5% of samples. Most patients (88.9%) showed low O6-methylguanine-DNA methyltransferase protein expression. O6-methylguanine-DNA methyltransferase methylation status was not correlated with any of the clinicopathological variables determined in rectal adenocarcinomas selected for chemoradiotherapy. Conclusion: O6-methylguanine-DNA methyltransferase methylation status is not correlated with clinicopathologic variables examined in rectal adenocarcinoma selected for chemoradiotherapy, although its role as a biomarker awaits further investigation.

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“…A phase I study evaluated the efficacy of radiotherapy and TMZ plus capecitabine-based chemotherapy in patients with locally advanced rectal cancer. Of the 22 patients included in the study, a CR was observed in seven patients (31.8%), of which 6 presented MGMT promoter methylation, suggesting a possible predictive role of MGMT promoter methylation status for TMZ response [ 143 ]. The same researchers are currently recruiting participants for a new phase II study (NCT03156036) designed to assess the potential benefit achieved by adding TMZ to this treatment regimen and to validate the predictive value of MGMT status.…”

Section: Temozolomide: Clinical Usementioning

confidence: 99%

Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications

Ortíz

Perazzoli

Cabeza

et al. 2021

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: Temozolomide (TMZ), an oral alkylating prodrug which delivers a methyl group to purine bases of DNA (O6- guanine; N7-guanine and N3-adenine), is frequently used together with radiotherapy as part of the first-line treatment of high-grade gliomas. The main advantages are its high oral bioavailability (almost 100% although the concentration found in the cerebrospinal fluid was approximately 20% of the plasma concentration of TMZ), its lipophilic properties, and small size that confer the ability to cross the blood-brain barrier. Furthermore, this agent has demonstrated activity not only in brain tumors but also in a variety of solid tumors. However, conventional therapy using surgery, radiation, and TMZ in glioblastoma results in a median patient survival of 14.6 months. Treatment failure has been associated with the tumor drug resistance. This phenomenon has been linked to the expression of O6-methylguanine-DNA methyltransferase, but the mismatch repair system and the presence of cancer stem-like cells in tumors have also been related to TMZ resistance. The understanding of these mechanisms is essential for the development of new therapeutic strategies in the clinical use of TMZ, including the use of nanomaterial delivery systems and the association with other chemotherapy agents. The aim of this review is to summarize the resistance mechanisms of TMZ and the current advances to improve its clinical use.

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Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer

Cited by 8 publications

References 34 publications

Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer

Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer

MGMT Promoter Methylation in Patients with Rectal Adenocarcinoma After Chemoradiotherapy Treatment: Clinical Implications

Temozolomide: An Updated Overview of Resistance Mechanisms, Nanotechnology Advances and Clinical Applications

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