Radiation Therapy, Mitomycin, and Either Fluorouracil or Cisplatin in Treating Patients With Locally Advanced Anal Cancer

• Response as measured by RECIST at 8 weeks after completion of study treatment (Phase II) [ Designated as safety issue: No ]
  
• Event-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III) [ Designated as safety issue: No ]
  

• Acute toxicity and compliance to treatment as measured by CTC v 2.0 at completion of study treatment (Phase II) [ Designated as safety issue: Yes ]
  
• Colostomy-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III) [ Designated as safety issue: No ]
  
• Overall survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter [ Designated as safety issue: No ]
  
• Disease-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter [ Designated as safety issue: No ]
  
• Local control as measured by Gray at 12 and 26 weeks, then every 6 months thereafter [ Designated as safety issue: No ]
  
• Late toxicity as measured by RTOG and EROTC every 6 months after week 26 [ Designated as safety issue: Yes ]
  
• Quality of life as measured by EORTC Quality of Life Questionnaire-C30 and ASCT at 12 and 26 weeks, then every 6 months for 2 years after entry [ Designated as safety issue: No ]
  

OBJECTIVES:

Phase II

• Primary

  • Compare the early clinical response (tumor response at 8 weeks) of patients with locally advanced anal cancer treated with radiotherapy with mitomycin and cisplatin vs mitomycin and fluorouracil.

• Secondary

  • Compare the feasibility of these regimens in these patients.
  • Compare the acute toxicity of these regimens in these patients.
  • Compare patient compliance to these regimens.

Phase III

• Primary

  • Compare the event-free survival of patients treated with these regimens.

• Secondary

  • Compare colostomy-free, disease-free, and overall survival of patients treated with these regimens.
  • Compare locoregional control in patients treated with these regimens.
  • Compare the late toxicity of these regimens in these patients.
  • Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, T stage (T2 vs T3 vs T4), and nodal status (N0 vs N+). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy once daily 5 days a week on weeks 1-4, 7-8, and 3 days of week 9 (total of 33 fractions). Patients concurrently receive fluorouracil IV continuously on days 1-26 and 43-59 and mitomycin IV over 15 minutes on days 1 and 43.
• Arm II: Patients receive radiotherapy and mitomycin as in arm I and cisplatin IV over 1 hour on days 1, 8, 15, 22, 43, 50, and 57.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at weeks 12 and 26, and then every 6 months for 2 years.

Patients are followed every 2 weeks for 8 weeks, at week 26, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 678 patients (80 [40 per treatment arm] for phase II and 598 [299 per treatment arm] for phase III) will be accrued for this study within 2-5 years.