Inclusion Criteria:

3.1.1 Histologically-proven, invasive primary squamous, basaloid, or cloacogenic carcinoma
of the anal canal; 3.1.2 AJCC 2009 TN Stage: T1N1-N3, T2(< 4cm)N1-N3, T2(> 4cm)N0,T3N0-3,
T4N0-3;based upon the following minimum diagnostic workup: 3.1.2.1 History/physical
examination within 14 days prior to registration; 3.1.2.2 Within 42 days prior to
registration, the patient must have an anal examination by any of the following:
colonoscopy, sigmoidoscopy, or rigid proctoscopy, with documentation of primary anal
lesion size, distance from anal verge.

3.1.3 Groin examination within 42 days prior to registration with documentation of any
groin adenopathy and lymphadenopathy (location: right vs. left; medial vs. lateral; mobile
vs. fixed; and size); 3.1.4 X-ray (PA and lateral), CT scan, or PET/CT scan of the chest
within 42 days prior to registration; 3.1.5 CT scan, MRI, or PET/CT of the abdomen and
pelvis within 42 days prior to registration; 3.1.6 Zubrod Performance Status 0-1; 3.1.7
Age ≥ 18; 3.1.8 Laboratory data obtained ≤ 14 days prior to registration on study, with
adequate bone marrow, hepatic and renal function defined as follows:

- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3;

- Platelets ≥ 100,000 cells/mm3;

- Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve
Hgb ≥ 8.0 g/dl is acceptable.);

- Serum creatinine ≤ 1.5 mg/dl;

- Bilirubin < 1.4mg/dl;

- ALT/AST < 3 x ULN;

- Negative serum pregnancy test for women of child-bearing potential; 3.1.9 Women of
childbearing potential and male participants must agree to use a medically effective
means of birth control throughout their participation in the treatment phase of the
study.

3.1.10 Patients must sign a study-specific informed consent prior to study entry.

3.1.11 Patients with a history of clinically significant pulmonary disease must have PFTs
demonstrating a DLCO ≥ 40%. This testing is considered standard of care prior to
mitomycin, 5-FU and radiation.

3.1.12 Patients with a history of clinically significant cardiac disease must have a
LVEF ≥ 30% by ECHO. (MUGA scan may also be used to determine LVEF) This testing is
considered standard of care prior to mitomycin, 5-FU and radiation.

Exclusion Criteria:

3.2.1 Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free
for a minimum of 2 years; 3.2.2 Prior systemic chemotherapy for anal cancer; 3.2.3 Prior
allergic reaction to the study drugs involved in this protocol. 3.2.4 Prior radiotherapy
to the pelvis that would result in overlap of radiation therapy fields; 3.2.5 Severe,
active co-morbidity, defined as follows: 3.2.5.1 Patients with uncontrolled intercurrent
illness including, but not limited to ongoing or active infection, symptomatic congestive
heart failure, unstable angina pectoris and cardiac arrhythmia are ineligible.
Furthermore, patients with unstable angina and/or congestive heart failure requiring
hospitalization within the past 6 months are ineligible; 3.2.5.2 Transmural myocardial
infarction within the last 6 months; 3.2.5.3 Acute bacterial or fungal infection requiring
intravenous antibiotics at the time of registration; 3.2.5.4 Chronic Obstructive Pulmonary
Disease exacerbation or other respiratory illness requiring hospitalization or precluding
study therapy at the time of registration; 3.2.5.5 Hepatic insufficiency resulting in
clinical jaundice and/or coagulation defects; 3.2.6 Patients known to be seropositive for
HIV and/or active hepatitis, even if liver function studies are in the eligible range.

3.2.7 Other immunocompromised status (e.g., organ transplant or chronic glucocorticoid
use).

3.2.8 Women who are pregnant or lactating are ineligible because the treatment involved in
this study may be significantly teratogenic and there is the potential for transmission of
listeria to the infant.

3.2.9 Patients allergic to penicillin, trimethoprim-sulfa and quinolones (including
history of rash or anaphylaxis).

3.2.10 Patients allergic to naproxen. 3.2.11 Patients receiving oral or IV antibiotics
3.2.11 Patients with a prior history of a splenectomy and/or sickle cell trait/disease