Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer

OBJECTIVES:

Primary

- Determine the 2-year local failure rate in patients with HIV-associated stage I-IIIB
anal carcinoma treated with cisplatin, fluorouracil, cetuximab, and radiotherapy.

- Determine the objective response rate (complete and partial), progression-free survival,
relapse-free survival, colostomy-free survival, overall survival, quality of life, and
overall toxicity in patients treated with this regimen.

Secondary

- Characterize the effect of this regimen on the underlying HIV condition by describing
changes in viral load, CD4 counts, and the incidence of opportunistic illnesses,
including the development of AIDS during and in the first year after treatment.

- Evaluate the effect of this regimen on anogenital human papilloma virus (HPV) infection
and anal cytology.

OUTLINE: This is an open-label, multicenter study.

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 35*, fluorouracil
IV continuously on days 1-4 and 29-32, and cisplatin IV over 1 hour on days 1 and 29.
Beginning on day 1, patients undergo concurrent radiotherapy to the primary tumor 5 days a
week for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable
toxicity.

NOTE: *Patients receiving 7 weeks of radiotherapy also receive cetuximab on days 42 and 49.

Quality of life is assessed at baseline, at the completion of study treatment, and then at
months 3, 6, 12, 24, and 36.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

- Histologically confirmed stage I-IIIB invasive anal canal or perianal (anal margin)
squamous cell carcinoma, including tumors with any of the following nonkeratinizing
histologies:

- Basaloid

- Transitional cell

- Cloacogenic

- Documented HIV infection by 1 of the following:

- Antibody detection

- Culture

- Quantitative assay of plasma HIV RNA

PATIENT CHARACTERISTICS:

- Karnofsky performance status 60-100%

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 10 g/dL (transfusions, epoetin alfa, or myeloid growth factor support
allowed provided blood counts are stable for ≥ 2 weeks prior to study entry)

- Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance > 60 mL/min

- AST and ALT ≤ 3 times ULN

- Bilirubin ≤ 2 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No acute active, serious, uncontrolled opportunistic infection

- No other prior invasive malignancy diagnosed within the past 24 months, excluding in
situ cervical cancer, anal dysplasia or carcinoma in situ, nonmelanoma skin carcinoma,
or Kaposi's sarcoma that has not required systemic chemotherapy within the past 24
months

- No peripheral neuropathy > grade 1

- No severe or poorly controlled diarrhea

- No medical or psychiatric illness that would preclude study requirements

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy or radiotherapy for this malignancy

- Prior radiotherapy for another condition (e.g., Kaposi's sarcoma) allowed