Amifostine to Protect the Rectum During External Beam Radiotherapy for Prostate Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Prostatic Neoplasms

Treatments: Radiation: Radiation therapy; Drug: Amifostine trihydrate

Study type: Interventional

Funder types: NIH

Identifiers

NCT00040365

020215

02-C-0215

Details and patient eligibility

About

This study will evaluate the safety and effectiveness of a drug called amifostine in reducing the bowel side effects of radiation treatment for prostate cancer. Amifostine is a 'radioprotector' medicine that to protects normal tissue from radiation damage. This study will determine whether placing amifostine in the rectum during radiation treatment for prostate cancer can decrease common side effects of treatment, including diarrhea, painful bowel movements, bleeding, and gas.

Patients 18 years of age or older with prostate cancer may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, bone scan if a recent one is not available, and possibly computed tomography (CT) and magnetic resonance imaging (MRI) scans of the pelvis. They will also have a liquid retention test, in which they are given an enema of 4 tablespoons of salt water that they must retain for 20 minutes.

Participants will receive standard radiation therapy for prostate cancer-5 consecutive days for 8 weeks-in the National Institutes of Health (NIH) Radiation Oncology Clinic. Amifostine will be placed in the rectum by a mini-enema before each radiation treatment so that it covers the lining of the rectum. To determine the side effects of the treatment, patients will undergo a proctoscopic examination before beginning radiation therapy, two times during therapy, and at each follow-up visit for 5 years after treatment ends. This examination involves inserting a proctoscope (a thin flexible tube with a light at the end) into the rectum and taking pictures.

Patients will be followed in the clinic at visits scheduled 1, 3, 6, 12, 18, 24, 36, 48, and 60 months after treatment for a physical examination and routine blood tests, proctoscopic examination, and review of bowel symptoms.

Full description

Normal tissue tolerance of the rectum limits the dose of radiation that can be delivered to the prostate for curative treatment of prostate cancer. Amifostine is a radioprotector, an agent that reduces tissue damage incurred by ionizing radiation. It has been well studied in humans and is approved for intravenous use. Rectal administration results in a preferential accumulation of Amifostine in the rectal mucosa, and neither free parent compound nor free active metabolite have been detected in systemic circulation. This trial proposes to observe the rate of early and late bowel toxicity in a group of patients with prostate cancer receiving standard high dose, 3D conformal external beam radiotherapy and concurrent intra-rectal applications of Amifostine. Primary measures of rectal toxicity (RTOG radiation morbidity scoring) will also be compared with self-assessment measures of quality of life, and rectal radiation dose as assessed by dose-volume histograms.

Enrollment: 30 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• INCLUSION CRITERIA:

Pathologically confirmed adenocarcinoma of the prostate gland.

Age greater than or equal to 18 years.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Informed consent: All patients must sign a document of informed consent indicating their understanding of the investigational nature and risks of the study before any protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility).

EXCLUSION CRITERIA:

Other active malignancy (except for non-melanoma skin cancer).

Patient with a prior history of pelvic or prostate radiotherapy.

Patients with chronic inflammatory bowel disease.

Patients with distant metastatic disease.

Cognitively impaired patients who cannot give informed consent.

Human Immunodeficiency Virus (HIV) positivity.

Other medical conditions deemed by the principal investigator (PI) or associates to make the patient ineligible for high dose radiotherapy.

Trial design

Primary purpose: Supportive Care

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Amifostine

Experimental group

Description:

1000 mg for the first 18 patients. 2000 mg for the last 12 patients. The syringe of amifostine will be connected to a rectal enema bottle for administration. Administered slowly over 30-60 seconds with the patient in recumbent position 30-45 minutes prior to each radiation treatment (33-39 doses).

Treatment:

Drug: Amifostine trihydrate

Radiation: Radiation therapy