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

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• 作者：Jae Ho Jeong ; MD^&lowast ; ; Yong Sang Hong ; MD ; PhD^&lowast ; ; Yangsoon Park ; MD ; PhD^&dagger ; ; Jihun Kim ; MD ; PhD^&dagger ; ; Jeong Eun Kim ; MD ; PhD^&lowast ; ; Kyu-pyo Kim ; MD ; PhD^&lowast ; ; Sun Young Kim ; MD ; PhD^&lowast ; ; Jin-hong Park ; MD ; PhD^&Dagger ; ; Jong Hoon Kim ; MD ; PhD^&Dagger ; ; In Ja Park ; MD ; PhD^§ ; ; Seok-Byung Lim ; MD ; PhD^§ ; ; Chang Sik Yu ; MD ; PhD^§ ; ; Jin Cheon Kim ; MD ; PhD^§ ; ; Tae Won Kim ; MD ; PhD^&lowast ; ; ^{twkimmd@amc.seoul.kr" class="auth_mail" title="E-mail the corresponding author}
• 刊名：International Journal of Radiation Oncology*Biology*Physics
• 出版年：2016
• 出版时间：1 October 2016
• 年：2016
• 卷：96
• 期：2
• 页码：289-295
• 全文大小：267 K

文摘

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 O⁶-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_anyN1-2 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.