Radiation Therapy, Fluorouracil, and Mitomycin in Treating Patients with Stage I-IIIB Anal Cancer

Inclusion Criteria

• Participants must have histologically or cytologically confirmed invasive squamous, basaloid, or cloacogenic carcinoma of the anal canal; pathology must be reviewed by the treating institution; patients must be clinically staged as T stage 1-4 and N0-N3 stage, based upon the following minimum diagnostic work-up: * History/physical examination within 42 days prior to registration * Anal examination with mandatory biopsy and any of the following: colonoscopy, sigmoidoscopy, rigid proctoscopy, or anoscopy; digital rectal examination (performed at the discretion of the treating physician) with documentation of primary anal lesion size, distance from the anal verge, and anal tone is also recommended * Groin examination with documentation of any groin adenopathy and lymphadenopathy (location: right vs. left, medial vs. lateral, mobile vs. fixed, and size) * A biopsy is not needed for pathologically enlarged or clinically suspicious inguinal, perirectal, or pelvic lymph nodes on examination, computed tomography (CT) scan, or positron emission tomography (PET)/CT and will be considered clinically positive * No evidence of distant metastatic disease as determined by CT scan with contrast, or PET/CT scan of the chest within 42 days prior to registration and CT scan with contrast, magnetic resonance imaging (MRI), or PET/CT of the abdomen and pelvis within 42 days prior to registration
• No prior abdominopelvic radiotherapy is allowed except for total body irradiation administered >= 10 years prior; no prior systemic therapy for anal cancer
• Life expectancy of greater than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Hemoglobin >= 8.0 g/dl (Note: use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable) (within 2 weeks prior to registration)
• Leukocytes >= 3,000/mcL (within 2 weeks prior to registration)
• Absolute neutrophil count >= 1,800/mcL (within 2 weeks prior to registration)
• Platelets >= 100,000/mcL (within 2 weeks prior to registration)
• Total bilirubin within normal institutional limits (within 2 weeks prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal (within 2 weeks prior to registration)
• Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for subjects with creatinine levels about institutional limits (within 2 weeks prior to registration)
• If there is clinical suspicion of acquired immunodeficiency syndrome (AIDS), a human immunodeficiency virus (HIV) test is recommended within 42 days prior to registration; Note: HIV positive patients without AIDS are eligible for enrollment on this study
• The effects of radiation on the developing human fetus are known to be teratogenic. Therefore, female participants must be either surgically sterile (via hysterectomy or bilateral tubal ligation), post-menopausal, or agree to use a medically effective means of birth control (hormonal or barrier method of birth control; abstinence) prior to study entry and throughout their participation in the treatment phase of this study; female participants of child bearing potential must also have a negative serum pregnancy test within 2 weeks prior to registration
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to mitomycin-C or 5-fluorouracil
• Prior surgery for cancer of the anus that removed all macroscopic anal cancer
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because proton radiotherapy is a/an teratogenic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with proton radiotherapy, breastfeeding should be discontinued if the mother is treated with proton radiotherapy. These potential risks may also apply to other agents used in this study
• Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; patients with known AIDS will be ineligible for this protocol; patients with clinical suspicion of AIDS and who are unwilling to have an HIV test are not eligible for this trial
• Other immunocompromised status (e.g. organ transplant)
• Individuals with a history of a different malignancy are ineligible except for the following circumstances: individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years or are deemed by the investigator to be at low risk for recurrence of that malignancy; individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
• Patients whose insurance will not cover proton therapy will still be eligible for the study