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Author 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
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword RADIOLOGY AND NUCLEAR MEDICINE ♦ CHEMOTHERAPY ♦ GY RANGE 01-10 ♦ GY RANGE 10-100 ♦ NEOPLASMS ♦ PATIENTS ♦ RADIATION DOSES ♦ RADIOTHERAPY ♦ RECTUM ♦ TOXICITY
Abstract Purpose: Preoperative chemoradiation therapy (CRT) with capecitabine is a standard treatment strategy in patients with locally advanced rectal cancer (LARC). Temozolomide improves the survival of patients with glioblastoma with hypermethylated O{sup 6}-methylguanine DNA methyltransferase (MGMT); MGMT hypermethylation is one of the colorectal carcinogenesis pathways. We aimed to determine the dose-limiting toxicity (DLT) and recommended dose (RD) of temolozomide in combination with capecitabine-based preoperative CRT for LARC. Methods and Materials: Radiation therapy was delivered with 45 Gy/25 daily fractions with coned-down boost of 5.4 Gy/3 fractions. Concurrent chemotherapy comprised fixed and escalated doses of capecitabine and temozolomide, respectively. The MGMT hypermethylation was evaluated in pretreatment tumor samples. This trial is registered with (ClinicalTrials.gov) with the number (NCT01781403). Results: Twenty-two patients with LARC of cT3-4N0 or cT{sub any}N1-2 were accrued. Dose level 3 was chosen as the RD because DLT was noticeably absent in 10 patients treated up to dose level 3. An additional 12 patients were recruited in this group. Grade III adverse events were noted, and pathologic complete response (pCR) was observed in 7 patients (31.8%); MGMT hypermethylation was detected in 16. The pCR rate was 37.5% and 16.7% in the hypermethylated and unmethylated MGMT groups, respectively (P=.616). Conclusions: There was a tendency toward higher pCR rates in patients with hypermethylated MGMT. Future randomized studies are therefore warranted.
ISSN 03603016
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-10-01
Publisher Place United States
Journal International Journal of Radiation Oncology, Biology and Physics
Volume Number 96
Issue Number 2


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