Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer
Condition: Anal Cancer
MeSH terms: Anus Neoplasms
Intervention: fluorouracil; mitomycin C; Intensity-modulated radiation therapy
Intervention description: 1000 mg/m^2/day 96-hour continous infusion (M-F) starting on day 1 and again on day 29 of radiation therapy.; 10 mg/m^2 intravenous therapy on day 1 and day 29 of radiation therapy.; Prescription dose depends on tumor staging.
T2N0: The primary tumor PTV (planning target volume) (PTVA) receives 50.4 Gy in 28 fractions (fx) at 1.8 Gy/fx. The nodal PTVs receive 42 Gy in 28 fx at 1.5 Gy/fx. PTVA receive 50.4 Gy in 28 fractions at 1.8 Gy/fx. PTV42 receive 42 Gy in 28 fx at 1.5 Gy/fx and will include all nodal regions.
T3N0 or T4N0: The primary tumor PTV (PTVA) will receive 54 Gy in 30 fx at 1.8 Gy/fx. The nodal PTVs will receive 45 Gy in 30 fx at 1.5 Gy/fx. PTVA will receive 54 Gy in 30 fx at 1.80 Gy/fx. PTV45 will receive 45 Gy in 30 fx electively at 1.5 Gy/fx and will include all nodal regions.
For N+ disease: The primary tumor PTV (PTVA) will receive 54 Gy in 30 fx at 1.8 Gy/fx. For involved nodes ≤ 3 cm in maximum dimension, the involved nodal PTV will receive 50.4 Gy in 30 fx at 1.68 Gy/fx. For involved nodes > 3 cm in maximum dimension, the involved nodal PTV will receive 54 Gy in 30 fx at 1.80 Gy/fx.
Intervention MeSH terms: Fluorouracil; Mitomycins; Mitomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: stage II anal cancer; stage IIIA anal cancer; stage IIIB anal cancer; basaloid carcinoma of the anus; cloacogenic carcinoma of the anus; squamous cell carcinoma of the anus

Summary:

      RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to
      the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in
      chemotherapy, such as fluorouracil and mitomycin C, work in different ways to stop the growth
      of tumor cells, either by killing the cells or by stopping them from dividing. Giving
      radiation therapy together with 5-fluorouracil (5-FU) and mitomycin C may kill more tumor
      cells.

      PURPOSE: This phase II trial is studying the side effects and how well giving
      intensity-modulated radiation therapy together with fluorouracil and mitomycin C works in
      treating patients with invasive anal cancer.
    

Eligibility criteria:

        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