Iles Sm, Gollins Sw, Susnerwala S, Haylock B, Myint S, Biswas A, Swindell R, Levine E
Department of Clinical Oncology, The Christie Hospital NHS Trust, Manchester M20 4BX, UK.
Br J Cancer. 2008 Apr 8;98(7):1210-6. doi: 10.1038/sj.bjc.6604292. Epub 2008 Mar 18.
In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n=12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m(-2) to 60 mg m(-2) to 70 mg m(-2) to identify the maximum tolerated dose (60 mg m(-2)). In phase II, 31 patients with non-resectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m(-2) per day) for 5 weeks. Irinotecan (60 mg m(-2)) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity.
在英国，10%的直肠癌确诊患者在初诊时就患有无法手术的疾病。本研究确定，给予静脉注射伊立替康、5-氟尿嘧啶（5-FU）和盆腔放疗是否能提高局部晚期无法手术的直肠癌的可切除率。在试验的第一阶段（n = 12），伊立替康的剂量在三个患者队列中从50 mg/m²逐步增加到60 mg/m²，再到70 mg/m²，以确定最大耐受剂量（60 mg/m²）。在第二阶段，31例无法切除的患者接受了45 Gy的放疗和5-FU输注（每天200 mg/m²），持续5周。伊立替康（60 mg/m²）在第1、8、15和22天给药。治疗后，如有可能，患者接受手术。30例患者完成了方案，28例接受了手术。手术前，24例患者的MRI重新分期显示，19例（79%）在治疗后肿瘤分期降低（7例完全临床缓解，12例部分缓解）。27例患者术后接受随访，22例（81%）切缘阴性。3年无病生存率和总生存率估计分别为65%和90%。该方案耐受性良好。伊立替康、5-FU和放疗可使肿瘤降级，从而能够切除先前无法手术的肿瘤，且毒性可接受。
