Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2¡Á2 factorial trial

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• 作者：Prof Roger D James ; FRCP^a ; ^&dagger ; ; Dr Robert Glynne-Jones ; FRCR^b ; ^&dagger ; ; ^{rob.glynnejones@nhs.net} ; Helen M Meadows ; MSc^c ; Prof David Cunningham ; MD^d ; Arthur Sun Myint ; FRCR^e ; Mark P Saunders ; FRCR^f ; Prof Timothy Maughan ; MD^g ; Alec McDonald ; MD^h ; Sharadah Essapen ; MDⁱ ; Martin Leslie ; MD^j ; Stephen Falk ; MD^k ; Charles Wilson ; MD^l ; Simon Gollins ; FRCR^m ; Rubina Begum ; BSc^c ; Prof Jonathan Ledermann ; MD^c ; Latha Kadalayil ; PhD^c ; Prof David Sebag-Montefiore ; FRCRⁿ
• 刊名：Lancet Oncology
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：14
• 期：6
• 页码：516-524
• 全文大小：247 K

文摘

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Summary

Background

Chemoradiation became the standard of care for anal cancer after the ACT I trial. However, only two-thirds of patients achieved local control, with 5-year survival of 50 % ; therefore, better treatments are needed. We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response, and whether maintenance chemotherapy after chemoradiation improves survival.

Methods

In this 2¡Á2 factorial trial, we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK. Patients were randomly assigned to one of four groups, to receive either mitomycin (12 mg/m² on day 1) or cisplatin (60 mg/m² on days 1 and 29), with fluorouracil (1000 mg/m² per day on days 1-4 and 29-32) and radiotherapy (50¡¤4 Gy in 28 daily fractions); with or without two courses of maintenance chemotherapy (fluorouracil and cisplatin at weeks 11 and 14). The random allocation was generated by computer and patients assigned by telephone. Randomisation was done by minimisation and stratified by tumour site, T and N stage, sex, age, and renal function. Neither patients nor investigators were masked to assignment. Primary endpoints were complete response at 26 weeks and acute toxic effects (for chemoradiation), and progression-free survival (for maintenance). The primary analyses were done by intention to treat. This study is registered at , number 26715889.

Findings

We enrolled 940 patients: 472 were assigned to mitomycin, of whom 246 were assigned to no maintenance, 226 to maintenance; 468 were assigned to cisplatin, of whom 246 were assigned to no maintenance, 222 to maintenance. Median follow-up was 5¡¤1 years (IQR 3¡¤9-6¡¤9). 391 of 432 (90¡¤5 % ) patients in the mitomycin group versus 386 of 431 (89¡¤6 % ) in the cisplatin group had a complete response at 26 weeks (difference ?0¡¤9 % , 95 % CI ?4¡¤9 to 3¡¤1; p=0¡¤64). Overall, toxic effects were similar in each group (334/472 [71 % ] for mitomycin vs 337/468 [72 % ] for cisplatin). The most common grade 3-4 toxic effects were skin (228/472 [48 % ] vs 222/468 [47 % ]), pain (122/472 [26 % ] vs 135/468 [29 % ]), haematological (124/472 [26 % ] vs 73/468 [16 % ]), and gastrointestinal (75/472 [16 % ] vs 85/468 [18 % ]). 3-year progression-free survival was 74 % (95 % CI 69-77; maintenance) versus 73 % (95 % CI 68-77; no maintenance; hazard ratio 0¡¤95, 95 % CI 0¡¤75-1¡¤21; p=0¡¤70).

Interpretation

The results of our trial¡ªthe largest in anal cancer to date¡ªshow that fluorouracil and mitomycin with 50¡¤4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK.

Funding

Cancer Research UK.