Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02. Issue 2 (February 2023)

• Record Type: Journal Article
• Authors: Oh, C.R.; Kim, J.E.; Lee, J.S.; Kim, S.Y.; Kim, T.W.; Choi, J.; Kim, J.; Park, I.J.; Lim, S.-B.; Park, J.-h.; Kim, J.H.; Choi, M.K.; Cha, Y.; Baek, J.Y.; Beom, S.-H.; Hong, Y.S.
• Is Part Of: Clinical oncology. Volume 35:Issue 2(2023)
• Page Start: e143
• Page End: e152
• Publication Date: 2023-02
• Subjects: MGMT -- neoadjuvant chemoradiotherapy -- rectal cancer -- temozolomide; MGMT O6-methylguanine DNA methyltransferase.; Oncology -- Periodicals; Tumors -- Periodicals; Cancer -- Treatment -- Periodicals; Radiotherapy -- Periodicals; Neoplasms -- Periodicals; Cancer -- Radiotherapy; Cancer -- Treatment; Oncology; Medical radiology; Radiotherapy; Tumors; Electronic journals; Periodicals; 616.994
• DOI: 10.1016/j.clon.2022.10.016
• Languages: English
• ISSNs: 0936-6555

Abstract

Abstract: Aims: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O 6 -methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. Materials and methods: LARC patients with clinical stage II (cT3-4N0) or III (cTany N+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. Results: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively ( P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1–2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. Conclusion: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy. Highlights: Achievement of pCR after CRT is associated with long-term survival in patients with LARC. We evaluated whether the addition of TMZ to fluoropyrimidine-based CRT can enhance the pCR rate. Adding TMZ tended to enhance the pCR rate and the benefit was greater in patients with MGMT methylation.