Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).
Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).
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在MRI定义的局部晚期直肠癌中，术前与同时使用的Irinotecan和Capecitabine进行了术前进行化学放疗：I期试验（NWCOG-2）。
DOI：
10.1038/sj.bjc.6605258
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发表时间：
2009-09-15
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究的目的是探讨术前使用放疗（RT）联合卡培他滨和伊立替康新辅助放化疗治疗局部晚期直肠癌的安全性。 MRI 扫描显示低危肿瘤具有威胁性（≤1mm）或累及直肠系膜筋膜，因此招募并治疗了 46 名患者。使用 3 或 4 个视野进行适形放疗，每日剂量为 1.8Gy，每周 5 天，总剂量为 45Gy。在整个放疗过程中，从第 1 至 35 天连续口服卡培他滨，每天两次，同时在放疗第 1 至 4 周期间每周静脉注射伊立替康一次。剂量水平如下逐渐升高。剂量水平 1：卡培他滨 650 mg m−2 b.i.d.和伊立替康 50 mg m−2；剂量水平 2：卡培他滨 650 mg m−2 b.i.d.和伊立替康 60 mg m−2；剂量水平 3：卡培他滨 825 mg m−2 b.i.d.和伊立替康 60 mg m2；剂量水平 4：卡培他滨 825 mg m−2 b.i.d.和伊立替康 70 mg m−2。腹泻（3级，无4级）是主要的严重急性毒性，伴有较轻程度的疲劳、中性粒细胞减少、厌食和掌跖红肿感觉。未来研究的推荐剂量为 2 级剂量，14 名患者中有 3 名 (21%) 出现 3 级腹泻。术后并发症包括七例盆腔或伤口感染以及两例吻合口和两例会阴伤口裂开。术后前30天内无死亡病例。在 41 个切除的标本中，11 个（27%）显示病理完全缓解（pCR），5 个（12%）显示受累的圆周切除边缘（定义为 ⩽1 mm）。 3 年无病生存率（意向治疗）为 53.2%。对于 MRI 定义的低风险局部晚期直肠癌威胁或累及直肠系膜的患者，术前放化疗以 45 Gy 放疗为基础，每天 25 次，持续 5 周，并连续每日口服卡培他滨 650 mg m−2 b.i.d.。第 1-35 天和第 1-4 周每周静脉注射 60mgm−2 伊立替康，可提供可接受的急性毒性和术后发病率，并具有令人鼓舞的反应和治愈性切除率。
The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (⩽1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m−2 b.i.d. and irinotecan 50 mg m−2; Dose level 2: capecitabine 650 mg m−2 b.i.d. and irinotecan 60 mg m−2; Dose level 3: capecitabine 825 mg m−2 b.i.d. and irinotecan 60 mg m2; Dose level 4: capecitabine 825 mg m−2 b.i.d. and irinotecan 70 mg m−2. Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as ⩽1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%. In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m−2 b.i.d. days 1–35 and weekly IV irinotecan at 60 mg m−2 weeks 1–4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates.
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影响因子：
8.8
作者：
Klautke, G;Küchenmeister, U;Foitzik, T;Ludwig, K;Prall, F;Klar, E;Fietkau, R
通讯作者：
Fietkau, R
影响因子：
45.3
作者：
Mohiuddin, M;Winter, K;Willett, C
通讯作者：
Willett, C
影响因子：
168.9
作者：
Quirke, Phil;Steele, Robert;Monson, John;Grieve, Robert;Khanna, Subhash;Couture, Jean;O'Callaghan, Chris;Myint, Arthur Sun;Bessell, Eric;Thompson, Lindsay C.;Parmar, Mahesh;Stephens, Richard J.;Sebag-Montefiore, David
通讯作者：
Sebag-Montefiore, David
影响因子：
158.5
作者：
Kapiteijn, E;Marijnen, CAM;van de Velde, CJH
通讯作者：
van de Velde, CJH
影响因子：
158.5
作者：
Sauer, R;Becker, H;Raab, R
通讯作者：
Raab, R