Authors: Dr. R. James et al Date posted: ASCO Oral Presentation June 2009

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A randomised trial of chemoradiation using mitomycin or cisplatin, with or without maintenance

cisplatin/5-FU in squamous cell carcinoma of the anus (ACT II)

Authors: Dr. R. James et al

Date posted: ASCO Oral Presentation June 2009

Reviewed by: Dr. Christopher Booth

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RCRT ComparisonAll pts received:50.4 Gy in 28 fractions 5-FU CIV 1000 mg/m2 D1-4 and 29-32Pts randomized to receive:1. Mitomycin 12 mg/m2 D1 only OR2. Cisplatin 60 mg/m2 D1 and 29

Maintenance Therapy Comparison1. No maintenance therapy after CRT2. 4 weeks after CRT pts received…5-FU CIV 1000 mg/m2 D1-4 and 29-32with Cisplatin 60 mg/m2 D1 and 29

T1-4 SCC anusNo mets

Adequate CrCl N=940

2x2 factorial design to evaluate:

1. Whether CRT using cisplatin or mitomycin produces a higher complete response rate (1° EP= path CR rate)

2. Whether maintenance therapy will improve local control or overall survival (1° EP=RFS)

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RESULTS

CRT – Mitomycin

CRT - Cisplatin

p-value

Path Complete response

95% 95% 0.53

Gr 3-4 toxicity

Heme

Non-heme

25%

60%

13%

65%

<0.001

0.17

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RESULTS

No Maintenance

Maintenance HR

3 yr RFS 75% 75% HR 0.94

p=0.67

3 yr OS 84% 85%HR 0.80

p=0.21

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STUDY COMMENTARY

• This trial sought to improve on outcomes in anal cancer by exploring whether Cisplatin should be substituted for Mitomycin and whether an additional cycle of maintenance chemotherapy should be given after CRT

• This large and well designed RCT did not find benefit to either of these interventions

• Cisplatin did not improve complete response rate or colostomy rate

• Maintenance therapy did not improve RFS or OS although follow-up is still relatively early

• There were no significant differences in the pattern of recurrence (i.e. local, regional, distant) among any of the 4 comparative strategies.

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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• This is the 2nd large RCT to evaluate whether cisplatin should replace Mitomycin in anal cancer

• The Intergroup RTOG-11 (JAMA 2008) did not find any improvement in outcome with the use of cisplatin in anal cancer

• These 2 RCTs suggest that the standard of care for patients with anal cancer continues to be chemoradiotherapy with 5-FU and Mitomycin