Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer

OBJECTIVES:

Primary

• Determine if dose-painted, intensity-modulated radiation therapy (IMRT), fluorouracil, and mitomycin C decreases the combined rate of gastrointestinal and genitourinary adverse events (grade II or greater) by at least 15% in the first 90 days after the start of treatment in patients with primary invasive carcinoma of the anal canal compared to patients treated on the radiotherapy, fluorouracil, and mitomycin C arm on clinical trial RTOG 98-11.

Secondary

• Determine the feasibility of performing IMRT in these patients in a cooperative group setting.
• Evaluate adverse events experienced by patients treated with this regimen and to decrease the grade 2 and higher and grade 3 and higher overall adverse event rates by 15% or 20% as compared to the radiotherapy and mitomycin C arm of RTOG 98-11.
• Evaluate the total duration of radiotherapy.
• Evaluate the efficacy of this regimen, in terms of locoregional failure, disease-free survival, time to colostomy, colostomy-free survival, and overall survival of these patients.
• Determine clinical complete response at 8 weeks after completion of study treatment.

OUTLINE: This is a multicenter study.

Patients receive mitomycin C IV over 10-30 minutes on days 1 and 29 and fluorouracil IV continuously over 96 hours on days 1-4 and 29-32. Patients also undergo dose-painted intensity-modulated radiation therapy once daily, 5 days a week, for 5½ to 6 weeks beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 59 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma of the anal canal, including any of the following subtypes:

• Squamous cell
• Basaloid
• Cloacogenic
• Primary invasive disease
• T2-4, N0-3 disease

• Clinically positive small inguinal nodes (i.e., < 1 cm in size) must be confirmed by biopsy (preferably fine-needle aspiration) within the past 6 weeks
• Biopsy is not required for enlarged inguinal, perirectal, or pelvic nodes on exam or CT scan that are found to be ≥ 1.0 cm and are considered to be clinically positive

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)
• ALT and AST < 3 times upper limit of normal
• Absolute neutrophil count ≥ 1,800/mm³
• Serum creatinine ≤ 1.5 mg/dL
• Platelet count ≥ 100,000/mm³
• Bilirubin < 1.4 mg/dL
• WBC ≥ 3,000/mm³
• INR ≤ 1.5
• No known AIDS

• HIV-positive patients without AIDS are eligible
• HIV test required for patients with clinical suspicion of AIDS
• No other invasive malignancy within the past 3 years except for nonmelanomatous skin cancer
• No severe, active comorbidity, defined as any of the following:

• Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
• Transmural myocardial infarction within the past 6 months
• Acute bacterial or fungal infection requiring IV antibiotics
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study treatment
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Uncontrolled diabetes mellitus, uncompensated heart disease, and/or uncontrolled high blood pressure, that in the opinion of the patient's treating physician, requires an immediate change in management

• Patients may be eligible if appropriate changes in management have resulted in adequate control of the above mentioned conditions
• Other immunocompromised status (e.g., organ transplantation or chronic glucocorticoid use)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior radiation therapy to the pelvis that would result in overlap of radiation therapy fields
• No prior systemic chemotherapy for cancer of the anus
• No prior surgery for cancer of the anus that removed all macroscopic anal cancer
• No concurrent sargramostim (GM-CSF)
• No concurrent amifostine