A Phase III Randomized study of 5-Fluorouracil, Mitomycin-C, and Radiotherapy in Carcinoma of the Anal Canal

Prinicipal Investigator: Ruby Meredith, M.D.

Objectives

1. Compare the initial and total local and distant failure rates in patients treated with either 5-FU plus mitomycin C concurrently with radiation therapy or induction 5-FU plus cisplatin followed by 5-FU plus cisplatin concurrently with radiation therapy.



2. Identify any differences in local control and colostomy rates at 2 years.



3. Determine any differences in colostomy-free, disease-free, or overall survival.

Patient Selection

Eligibility Criteria

1. Histologically proven squamous, basaloid, or cloacogenic carcinoma of the anal canal, other than carcinoma in situ (patients with local or regional recurrence after local excision or abdominal perineal resection are not eligible).



2. Patients must be > 18 years of age.



3. Performance status > 60 Karnofsky.



4. T stage 2-4 (see Appendix III).



5. Any N stage (eligible only if pelvic or inguinal; see Appendix III).



6. Study-specific consent form must be signed prior to randomization.



7. Adequate hepatic, renal and bone marrow function: Cratinine < 1.5 mg/dl (or cratinine clearance 80 ml/min if serum creatinine level is > 1.5 mg/dl); bilirubin < 1.4 mg/dl; WBC > 4000/ul; ANC > 1800ul; platelet count > 100,000.
   

   Creatinine clearance determined by 24 hour collection or nomogram:

   CrCl male =

   (140 - age) x (wt. as kg)
   (Serum Cr) x 72

   CrCl female=

   0.85 x (CrCl male)

Ineligibility Criteria

1. Karnofsky Performance status < 60.



2. Patients with histologies other than those listed in Section 3.1.1 are ineligible.



3. T1 tumors (2 cm) or evidence of distance metastases (M1).



4. Previous radiation or chemotherapy. Prior surgery for cancer of the anus, except biopsy.



5. Other malignancies (excluding non-melanomatous skin neoplasms) unless successfully treated and disease-free five years.



6. Presence of an active systemic infection, uncontrolled diabetes, uncompensated heart disease or uncontrolled high blood pressure.



7. Patients mental condition and social support is such that he or she can neither understand the nature of the protocol nor can comply with its requirements.



8. Patients with AIDS.



9. Pregnant or lactating women; patients of childbearing potential must agree to practice an effective method of contraception since pelvic irradiation and chemotherapy are hazardous to the fetus.

Treatment Plan:

Radiation Therapy

5-FU plus Mitomycin C Regimen (Arm 1) OR
5-FU plus Cisplatin Regimen (Arm 2)

Registration

For more information about this protocol, please contact the Radiation Oncology Division at (205) 934-2760.