Jae Ho Jeong1, Yong Sang Hong1, Yangsoon Park2, Jihun Kim2, Jeong Eun Kim1, Kyu-Pyo Kim1, Sun Young Kim1, Jin-Hong Park3, Jong Hoon Kim3, In Ja Park4, Seok-Byung Lim4, Chang Sik Yu4, Jin Cheon Kim4, Tae Won Kim5. 1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 2. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 3. Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 4. Department of Colorectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. 5. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address: twkimmd@amc.seoul.kr.
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(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 cTanyN1-2 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.
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(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 cTanyN1-2 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.
Authors: Jaime A. Oliver; Jaime Gómez-Millán; Jose A. Medina; Laura Cabeza; Gloria Perazzoli; Cristina Jimenez-Luna; Kevin Doello; Raúl Ortiz Journal: Balkan Med J Date: 2019-06-14 Impact factor: 2.021