Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer

Radiation Therapy Oncology Group

Status and phase

Completed

Phase 2

Conditions

Anal Cancer

Treatments

Drug: fluorouracil

Radiation: Intensity-modulated radiation therapy

Drug: mitomycin C

Study type

Interventional

Funder types

Other

NETWORK

NIH

Identifiers

NCT00423293

CDR0000524057

RTOG-0529

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Primary

Determine if dose-painted, intensity-modulated radiation therapy (IMRT), fluorouracil, and mitomycin C decreases the combined rate of gastrointestinal and genitourinary adverse events (grade II or greater) by at least 15% in the first 90 days after the start of treatment in patients with primary invasive carcinoma of the anal canal compared to patients treated on the radiotherapy, fluorouracil, and mitomycin C arm on clinical trial RTOG 98-11.

Secondary

Determine the feasibility of performing IMRT in these patients in a cooperative group setting.
Evaluate adverse events experienced by patients treated with this regimen and to decrease the grade 2 and higher and grade 3 and higher overall adverse event rates by 15% or 20% as compared to the radiotherapy and mitomycin C arm of RTOG 98-11.
Evaluate the total duration of radiotherapy.
Evaluate the efficacy of this regimen, in terms of locoregional failure, disease-free survival, time to colostomy, colostomy-free survival, and overall survival of these patients.
Determine clinical complete response at 8 weeks after completion of study treatment.

OUTLINE: This is a multicenter study.

Patients receive mitomycin C IV over 10-30 minutes on days 1 and 29 and fluorouracil IV continuously over 96 hours on days 1-4 and 29-32. Patients also undergo dose-painted intensity-modulated radiation therapy once daily, 5 days a week, for 5½ to 6 weeks beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 59 patients will be accrued for this study.

Enrollment

63 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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