Department of Radiotherapy, Institute of Oncology, Ljubljana, Slovenia.
Eur J Surg Oncol. 2010 Mar;36(3):244-50. doi: 10.1016/j.ejso.2009.12.002. Epub 2009 Dec 29.
Neoadjuvant chemoradiotherapy (CRT) reduces local tumor recurrence in locally advanced rectal cancer (LARC). This phase II study assessed neoadjuvant cetuximab with capecitabine-based CRT in LARC.
Patients with stage II/III LARC received capecitabine 1250 mg/m(2) twice daily for 2 weeks followed by intravenous cetuximab 400 mg/m(2) at week 3, then weekly intravenous 250 mg/m(2) cetuximab plus CRT including capecitabine 825 mg/m(2) twice daily (including weekends during radiotherapy) with radiotherapy of 45 Gy (25 x 1.8 Gy), 5 days a week for 5 weeks. Total mesorectal excision was scheduled 4-6 weeks following completion of CRT. The primary endpoint was pathological complete response (pCR).
Thirty-seven patients were eligible for safety and efficacy. TMN staging at baseline was: T4N2, 11%; T3N2, 40%; T2N2, 3%; T3N1, 35%; T2N1, 3% and T3N0 8%. The most common adverse events included, grade 1/2 acneiform skin rash (86%), and grade 3 radiodermatitis, (16%), diarrhea (11%) and hypersensitivity (5%). pCR was achieved in 3 patients (8%). Overall-, T- and N-downstaging rates were 73%, 57% and 81% respectively. Total sphincter preservation rate was 76%, and 53% in 17 patients whose tumors were located within 5 cm from the anal verge. Non-fatal perioperative complications occurred in 13 patients (35%) with delayed wound healing occurring in 6 patients (16%). One death was recorded due to sepsis following colonic necrosis.
Neoadjuvant cetuximab with capecitabine-based CRT is tolerable in patients with resectable LARC. Whilst the pCR rate was similar to recent reports, a high pathological downstaging rate was achieved.
新辅助放化疗（CRT）可降低局部晚期直肠癌（LARC）的局部肿瘤复发率。本 II 期研究评估了新辅助西妥昔单抗联合卡培他滨 CRT 治疗 LARC。
II/III 期 LARC 患者接受卡培他滨 1250 mg/m2 每日 2 次，共 2 周，然后在第 3 周给予静脉西妥昔单抗 400 mg/m2，随后每周给予静脉西妥昔单抗 250 mg/m2，联合 CRT，包括卡培他滨 825 mg/m2 每日 2 次（包括放疗期间的周末），放疗剂量为 45 Gy（25 x 1.8 Gy），每周 5 天，共 5 周。CRT 完成后 4-6 周行全直肠系膜切除术。主要终点为病理完全缓解（pCR）。
37 例患者可评估疗效和安全性。基线时的 TMN 分期为：T4N2，11%；T3N2，40%；T2N2，3%；T3N1，35%；T2N1，3%；T3N0，8%。最常见的不良反应包括 1/2 级痤疮样皮疹（86%）、3 级放射性皮炎（16%）、腹泻（11%）和过敏反应（5%）。3 例患者（8%）达到 pCR。总体、T 分级和 N 分级的降期率分别为 73%、57%和 81%。总保肛率为 76%，肿瘤距肛缘<5cm 的 17 例患者中为 53%。13 例（35%）患者发生非致命性围手术期并发症，其中 6 例（16%）发生延迟性伤口愈合。1 例患者因结肠坏死继发败血症死亡。
可切除的 LARC 患者应用西妥昔单抗联合卡培他滨 CRT 是可耐受的。尽管 pCR 率与近期报道相似，但达到了较高的病理降期率。
