肛管癌治疗进展

doi:10.3877/cma.j.issn.2095-3224.2016.01.06

肛管癌的发病在过去几十年明显升高，并且未来也将呈持续升高态势。随着对于肛管癌生物学行为的认识深入，治疗模式发生了根本性的改变。主要的治疗手段已经不再是有创的手术切除，放射治疗同步化疗不仅可以达到根治目的，而且避免了腹会阴联合切除术给患者带来人工肛门的困扰。同步放化疗作为一线治疗，其应用越来越广泛。5氟尿嘧啶＋丝裂霉素在肛管癌的治疗中有明确的作用，可以提高完全缓解率、提高保肛率和无病生存率。当患者在同步放化疗结束后仍有肿瘤残存时，可以尝试挽救性同步放化疗或密切随诊，如果随诊肿瘤进展再行手术挽救。IMRT技术的应用，利于提高肛门区癌的剂量，同时保护小肠、膀胱、皮肤和股骨头等周围器官从而降低治疗副反应，减少治疗中断时间。靶向药物的应用给肛门癌的治疗带来了新的选择，但是有效性和安全性，需要更多研究数据支持。

关键词: 肛管, 治疗, 同步放化疗, 进展

The incidence of anal cancer has increased significantly in the past few decades, and it will present a rising trend in the future. As for deeper understanding of the biological behavior of anal cancer, the treatment modality has changed. Primary treatment is no longer invasive surgical resection, concurrent chemo-radiotherapy could not only achieve the curative purpose, but also avoid the abdominal perineal resection of patients with poor quality of life. Concurrent chemo-radiotherapy as first-line treatment of anal cancer, which has been proven by many studies, is applied more and more widely. 5-fluorouracil and mitomycin C as concurrent chemotherapy regimen could improve the complete remission rate, sphincter preservation rate and disease-free survival rate. Residual tumor after concurrent chemo-radiotherapy could be treated by salvage surgery. The application of IMRT technology could improve the dosimetry of radiotherapy, while protecting the small intestine, bladder, skin and the femoral head to reduce the side effects of treatment, to minimize the interruption of treatment. Molecular targeted drugs added to the treatment of anal cancer has brought new options, but the effectiveness and safety of the combination need more results from more prospective studies.

Key words: Anal canal, Treatment, Concurrent chemo-radiotherapy, Progress

表1 同步放化疗与单纯放疗比较的研究表

研究（年份）	入组条件	放疗	同步化疗	分组	病例数	结肠造瘘率	P值	局部区域复发率	P值	总生存率	p值
UKCCCR（1996）	肛管或肛周癌，可局部切除T1病变以外的任何分期	45 Gy/20~25 F完成6周后评价肿瘤缩小≥50%的患者建议加量15 Gy/6 F或I192插植	5FU（1000 mg/㎡/d, d1~4或者750 mg/㎡/d, d1~5）civ，分别于放疗第一周和最后一周给予；MMC iv（12 mg/㎡），d1	RT＋5FU＋MMC	292	24%	-	3 y 30%	<0.001	3 y 65%	0.12
UKCCCR（1996）	肛管或肛周癌，可局部切除T1病变以外的任何分期	45 Gy/20~25 F完成6周后评价肿瘤缩小≥50%的患者建议加量15 Gy/6 F或I192插植		RT	285	40%	-	3 y 53%	<0.001	3 y 60%	0.12
EORTC（1997）	肛管或肛周癌，T3-4N0-3或T1-2N1-3，PS 0~1，年龄<76岁	45 Gy/25 F完成6周后加量（完全缓解者15 Gy/6 F，未完全缓解者20 Gy）	5FU 750 mg/㎡/d, d1~5, d29~33, civ；MMC iv 15 mg/㎡，d1	RT＋5FU＋MMC	51	5 y 28%	0.002	5 y 32%	0.02	5 y 58%	0.17
EORTC（1997）	肛管或肛周癌，T3-4N0-3或T1-2N1-3，PS 0~1，年龄<76岁	45 Gy/25 F完成6周后加量（完全缓解者15 Gy/6 F，未完全缓解者20 Gy）	5FU 750 mg/㎡/d, d1~5, d29~33, civ；MMC iv 15 mg/㎡，d1	RT	52	5 y 60%	0.002	5 y 48%	0.02	5 y 53%	0.17

表1 同步放化疗与单纯放疗比较的研究表

研究（年份）	入组条件	放疗	同步化疗	分组	病例数	结肠造瘘率	P值	局部区域复发率	P值	总生存率	p值
UKCCCR（1996）	肛管或肛周癌，可局部切除T1病变以外的任何分期	45 Gy/20~25 F完成6周后评价肿瘤缩小≥50%的患者建议加量15 Gy/6 F或I192插植	5FU（1000 mg/㎡/d, d1~4或者750 mg/㎡/d, d1~5）civ，分别于放疗第一周和最后一周给予；MMC iv（12 mg/㎡），d1	RT＋5FU＋MMC	292	24%	-	3 y 30%	<0.001	3 y 65%	0.12
UKCCCR（1996）	肛管或肛周癌，可局部切除T1病变以外的任何分期	45 Gy/20~25 F完成6周后评价肿瘤缩小≥50%的患者建议加量15 Gy/6 F或I192插植		RT	285	40%	-	3 y 53%	<0.001	3 y 60%	0.12
EORTC（1997）	肛管或肛周癌，T3-4N0-3或T1-2N1-3，PS 0~1，年龄<76岁	45 Gy/25 F完成6周后加量（完全缓解者15 Gy/6 F，未完全缓解者20 Gy）	5FU 750 mg/㎡/d, d1~5, d29~33, civ；MMC iv 15 mg/㎡，d1	RT＋5FU＋MMC	51	5 y 28%	0.002	5 y 32%	0.02	5 y 58%	0.17
EORTC（1997）	肛管或肛周癌，T3-4N0-3或T1-2N1-3，PS 0~1，年龄<76岁	45 Gy/25 F完成6周后加量（完全缓解者15 Gy/6 F，未完全缓解者20 Gy）	5FU 750 mg/㎡/d, d1~5, d29~33, civ；MMC iv 15 mg/㎡，d1	RT	52	5 y 60%	0.002	5 y 48%	0.02	5 y 53%	0.17

表2 放疗同步不同化疗方案比较的研究表

研究（年份）	入组条件	放疗	分组	化疗方案	病例数	结肠造瘘率	P值	局部区域复发率	P值	总生存率	P值	无病生存率	P值
RTOF8704/ECOG1289(1996)	肛管癌，任何T或N分期，KPS≥60分	45 Gy/25 F完成4~6周后未完全缓解者加量9 Gy/5 F	RT+5FU/MMC	5FU 750 mg/m²/d, d1~5, d29~33, civ; MMC iv 10 mg/m², d1, d29	146	4 y 9%	0.002	4 y 16%	0.0008	4 y 76%	0.31	4 y 73%	0.0003
RTOF8704/ECOG1289(1996)	肛管癌，任何T或N分期，KPS≥60分	45 Gy/25 F完成4~6周后未完全缓解者加量9 Gy/5 F	RT+5FU	FU 750 mg/m²/d, d1~5, d29~33, civ	145	4 y 22%	0.002	4 y 34%	0.0008	4 y 67%	0.31	4 y 51%	0.0003
RTOG9811(1997, 2012)	肛管癌，T2-4任何NM0，KPS ≥60，年龄≥18岁	45 Gy/25 F	RT+5FU/MMC	5FU 1000 mg/m²/d, d1~4, d29~32, civ; MMC iv 10 mg/m², d1, d29	325	5 y 10%	0.02	5 y 25%	0.07	5 y 75%	0.10	5 y 60%	0.17
RTOG9811(1997, 2012)	肛管癌，T2-4任何NM0，KPS ≥60，年龄≥18岁	45 Gy/25 F, T3T4N+或者T2残存立即计量10~14 Gy/5~7 f完成6周后量	5FU/DDP x2RT+5FU/DDP	5FU 1000 mg/m²/d, d1~4, 29~32, 57~60, 85~88; DDP 75 mg/m², d1, 29, 57, 85	324	5 y 19%	0.02	5 y 33%	0.07	5 y 70%	0.10	5 y 54%	0.17
ACCORD03(2012)	肛管鳞癌，T2-4任何NM0或T1-2N1-3M0, PS 0~1,年龄18~80	45 Gy/25 F加量15~20 Gy	5FU/DDP x2 RT+5FU/DDP	5FU 800 mg/m²/d, civ, d1~4; DDP 80 mg/m², d1; W1, 5, 9, 12	150	-	-	-	-	5 y 74.5%	0.81	-	-
ACCORD03(2012)	肛管鳞癌，T2-4任何NM0或T1-2N1-3M0, PS 0~1,年龄18~80	45 Gy/25 F加量15~20 Gy	RT+5FU/DDP	5FU 800 mg/m²/d, civ, d1~4; DDP 80 mg/m², d1; W1, 5	157	-	-	-	-	5 y 71%	?	-	-
ACT II	肛管或肛周癌，任何T任何NM0	50.4 Gy/28 F	RT+5FU/MMC	5FU 1000 mg/m²/d, civ, d1~4, 29~32; MMC iv 12 mg/m², d1	246	23%	-	?	-	DDP:77% MMC:79%辅助：76%未辅助：79%	NS	?	NS
			RT+5FU/DDP	5FU 1000 mg/m²/d, civ, d1~4, 29~32; DDP 60 mg/m², d1, 29	246	26%		?				?
			RT+5FU/MMC-5FU/DDP	5FU 1000 mg/m²/d, civ, d1~4, 29~32; MMC iv 12 mg/m², d1辅助化疗5FU 1000 mg/m²/d, civ, d71~74, 92~95; DDP 60 mg/m², d71, 92	226	23%		?				?
			RT+5FU/DDP-5FU/DDP	5FU 1000 mg/m²/d, civ, d1~4, 29~32; DDP 60 mg/m², d1, 29辅助化疗同上	222	22%		?				?

表2 放疗同步不同化疗方案比较的研究表

研究（年份）	入组条件	放疗	分组	化疗方案	病例数	结肠造瘘率	P值	局部区域复发率	P值	总生存率	P值	无病生存率	P值
RTOF8704/ECOG1289(1996)	肛管癌，任何T或N分期，KPS≥60分	45 Gy/25 F完成4~6周后未完全缓解者加量9 Gy/5 F	RT+5FU/MMC	5FU 750 mg/m²/d, d1~5, d29~33, civ; MMC iv 10 mg/m², d1, d29	146	4 y 9%	0.002	4 y 16%	0.0008	4 y 76%	0.31	4 y 73%	0.0003
RTOF8704/ECOG1289(1996)	肛管癌，任何T或N分期，KPS≥60分	45 Gy/25 F完成4~6周后未完全缓解者加量9 Gy/5 F	RT+5FU	FU 750 mg/m²/d, d1~5, d29~33, civ	145	4 y 22%	0.002	4 y 34%	0.0008	4 y 67%	0.31	4 y 51%	0.0003
RTOG9811(1997, 2012)	肛管癌，T2-4任何NM0，KPS ≥60，年龄≥18岁	45 Gy/25 F	RT+5FU/MMC	5FU 1000 mg/m²/d, d1~4, d29~32, civ; MMC iv 10 mg/m², d1, d29	325	5 y 10%	0.02	5 y 25%	0.07	5 y 75%	0.10	5 y 60%	0.17
RTOG9811(1997, 2012)	肛管癌，T2-4任何NM0，KPS ≥60，年龄≥18岁	45 Gy/25 F, T3T4N+或者T2残存立即计量10~14 Gy/5~7 f完成6周后量	5FU/DDP x2RT+5FU/DDP	5FU 1000 mg/m²/d, d1~4, 29~32, 57~60, 85~88; DDP 75 mg/m², d1, 29, 57, 85	324	5 y 19%	0.02	5 y 33%	0.07	5 y 70%	0.10	5 y 54%	0.17
ACCORD03(2012)	肛管鳞癌，T2-4任何NM0或T1-2N1-3M0, PS 0~1,年龄18~80	45 Gy/25 F加量15~20 Gy	5FU/DDP x2 RT+5FU/DDP	5FU 800 mg/m²/d, civ, d1~4; DDP 80 mg/m², d1; W1, 5, 9, 12	150	-	-	-	-	5 y 74.5%	0.81	-	-
ACCORD03(2012)	肛管鳞癌，T2-4任何NM0或T1-2N1-3M0, PS 0~1,年龄18~80	45 Gy/25 F加量15~20 Gy	RT+5FU/DDP	5FU 800 mg/m²/d, civ, d1~4; DDP 80 mg/m², d1; W1, 5	157	-	-	-	-	5 y 71%	?	-	-
ACT II	肛管或肛周癌，任何T任何NM0	50.4 Gy/28 F	RT+5FU/MMC	5FU 1000 mg/m²/d, civ, d1~4, 29~32; MMC iv 12 mg/m², d1	246	23%	-	?	-	DDP:77% MMC:79%辅助：76%未辅助：79%	NS	?	NS
			RT+5FU/DDP	5FU 1000 mg/m²/d, civ, d1~4, 29~32; DDP 60 mg/m², d1, 29	246	26%		?				?
			RT+5FU/MMC-5FU/DDP	5FU 1000 mg/m²/d, civ, d1~4, 29~32; MMC iv 12 mg/m², d1辅助化疗5FU 1000 mg/m²/d, civ, d71~74, 92~95; DDP 60 mg/m², d71, 92	226	23%		?				?
			RT+5FU/DDP-5FU/DDP	5FU 1000 mg/m²/d, civ, d1~4, 29~32; DDP 60 mg/m², d1, 29辅助化疗同上	222	22%		?				?

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The progress in the treatment of anal canal cancer

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The progress in the treatment of anal canal cancer