skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

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 amore » tendency toward higher pCR rates in patients with hypermethylated MGMT. Future randomized studies are therefore warranted.« less

Authors:
;  [1]; ;  [2]; ; ;  [1]; ;  [3]; ; ; ;  [4];  [1]
  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
  2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
  3. Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
  4. Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)
Publication Date:
OSTI Identifier:
22645643
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; GY RANGE 01-10; GY RANGE 10-100; NEOPLASMS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; RECTUM; TOXICITY

Citation Formats

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, and Kim, Tae Won, E-mail: twkimmd@amc.seoul.kr. Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.05.009.
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, E-mail: twkimmd@amc.seoul.kr. Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer. United States. doi:10.1016/J.IJROBP.2016.05.009.
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, and Kim, Tae Won, E-mail: twkimmd@amc.seoul.kr. Sat . "Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer". United States. doi:10.1016/J.IJROBP.2016.05.009.
@article{osti_22645643,
title = {Phase 1 Study of Preoperative Chemoradiation Therapy With Temozolomide and Capecitabine in Patients With Locally Advanced Rectal Cancer},
author = {Jeong, Jae Ho and Hong, Yong Sang and Park, Yangsoon and Kim, Jihun and Kim, Jeong Eun and Kim, Kyu-pyo and Kim, Sun Young and Park, Jin-hong and Kim, Jong Hoon and Park, In Ja and Lim, Seok-Byung and Yu, Chang Sik and Kim, Jin Cheon and Kim, Tae Won, E-mail: twkimmd@amc.seoul.kr},
abstractNote = {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.},
doi = {10.1016/J.IJROBP.2016.05.009},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 96,
place = {United States},
year = {Sat Oct 01 00:00:00 EDT 2016},
month = {Sat Oct 01 00:00:00 EDT 2016}
}