高剂量放疗（60 Gy）联合优福定/亚叶酸钙治疗不可切除局部晚期直肠癌（LARC）患者的II期试验长期结果

Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with non-resectable locally advanced rectal cancer (LARC).

作者信息

Vestermark Lene W, Jacobsen Anders, Qvortrup Camilla, Hansen Flemming, Bisgaard Claus, Baatrup Gunnar, Rasmussen Peter, Pfeiffer Per

机构信息

Odense University Hospital, Odense, Denmark.

出版信息

Acta Oncol. 2008;47(3):428-33. doi: 10.1080/02841860701798866.

DOI:10.1080/02841860701798866

PMID:18348002

Abstract

BACKGROUND

Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery.

METHODS

Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m(2) plus l-leucovorin 22.5 mg 5/7 days (divided in three doses).

RESULTS

From September 2000 to November 2004, 52 patients (median age 60 years (32-83); median PS 0 (0-2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25-49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27-112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6-45.2 months). Twenty-one patients (40%) are still alive June 2007.

CONCLUSIONS

Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.

摘要

背景

术前放化疗是不可切除的局部晚期直肠癌（LARC）患者治疗的基石。为改善治疗效果（R0切除率和生存率），高剂量放疗（RT）联合口服优福定/亚叶酸钙，以使肿瘤在预期根治性手术前缩小。

方法

盆腔放疗采用兆伏级光子，运用5野技术。放疗基于CT进行，每周5天，通过一个后野和两个侧野给予（48.6 Gy/27次分割），以覆盖原发肿瘤和区域淋巴结。此外，瘤床接受同步加量照射（5.4 Gy/27次分割）和最终加量照射（6 Gy/3次分割）；因此，大体肿瘤体积（GTV）接受60 Gy/30次分割。放疗期间，患者同时接受每日剂量的口服优福定300 mg/m²加亚叶酸钙22.5 mg，每周5天（分三次给药）。

结果

2000年9月至2004年11月，52例LARC患者（中位年龄60岁（32 - 83岁）；中位体能状态0（0 - 2））（36例原发，16例复发）纳入本II期研究。除3例患者外，所有患者均接受了计划的60 Gy放疗，放疗中位持续时间为42天（25 - 49天）。毒性反应非常轻微；只有4例患者减少了优福定剂量。未观察到具有临床意义的血液学毒性。经常观察到1级非血液学毒性（胃肠道毒性、疲劳和/或排尿困难），但只有4例患者出现3级毒性（腹泻和/或恶心/呕吐）。40例患者（77%）在放疗结束后中位55天（27 - 112天）接受了手术（30例R0切除，5例R1切除，5例R2切除）。7例（13%）患者达到病理完全缓解（pCR）。31例患者（60%）在中位25.4个月（1.6 - 45.2个月）后死亡。截至2007年6月，21例患者（40%）仍存活。