Department of Radiotherapy, Institut Gustave-Roussy, Villejuif.
Ann Oncol. 2013 Nov;24(11):2834-8. doi: 10.1093/annonc/mdt368. Epub 2013 Sep 11.
The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC).
Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT.
The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%), respectively.
CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings.
2007-007029-38.
ACCORD16 二期试验旨在评估局部晚期肛门癌（LAACC）患者在接受常规放化疗（CRT）联合西妥昔单抗治疗后的客观缓解率。
免疫功能正常的组织学确诊的 LAACC 患者接受 CRT [45 戈瑞（Gy）]，共 25 个分次，在 5 周内进行，第 1 周和第 5 周给予氟尿嘧啶和顺铂），每周给予西妥昔单抗剂量（250mg/m2，负荷剂量为 400mg/m2，在照射前 1 周），并给予标准剂量加量（20Gy）。该试验最初设计纳入 81 例患者，以检测新联合治疗与 CRT 相比，客观缓解率提高 15%。
在 16 例患者中有 14 例发生 15 例严重不良事件（SAE）后，该试验提前停止。5 例患者接受了全部计划治疗，方案修改后依从性更高。在 15 例 SAE 中，有 6 例是意外的。88%的患者发生了 3/4 级急性毒性作用（G），主要为全身（n=13，81%）、消化道（n=9，56%）、皮肤（n=5，31%）、感染（n=4，25%）、血液学（n=3，19%）和其他（n=9）；3 例患者发生 6 例 3/4 级迟发性毒性作用。无治疗相关死亡报告。11 例可评估患者治疗结束后 2 个月均有客观反应，包括完全缓解 6 例（55%）和部分缓解 5 例（45%）。13 例患者接受中位随访 22 个月[95%置信区间（CI）：18-27]，1 年无结直肠造口术生存率、无进展生存率和总生存率分别为 67%（95%CI：40%-86%）、62%（95%CI：36%-82%）和 92%（95%CI：67%-99%）。
在这组患者中，CRT 联合西妥昔单抗的毒性不可接受。正在等待其他评估该联合治疗的二期试验结果来证实这些发现。
EUDRA CT 编号：2007-007029-38。
