Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Local control of carcinoma of the prostate, when treated with radiation therapy, is dose related. It is well documented that higher radiation doses can produce definitive improvement but not without an increased risk of developing gastrointestinal and/or genitourinary toxicities. Radioprotective agents, such as amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD), have been proven to reduce radiotherapy-induced toxicities to normal tissue in patients with head and neck, thoracic, and pelvic tumors. Based on this information, and in an effort to determine the effectiveness of radioprotective agents in patients with prostate cancer, our institution developed a protocol involving use of amifostine in patients with prostate cancer treated with external beam radiation to a total dose of 45 Gy and/or high-dose rate brachytherapy. High-dose rate doses are 6 Gy times three fractions for combined therapy and 9.3 Gy times four fractions for the monotherapy group. To date, 13 patients have been treated, with preliminary results indicating an acceptably low incidence of gastrointestinal and genitourinary toxicities, including no acute blood pressure changes or skin reactions. However, there have been three cases of severe cardiopulmonary events, which are discussed in detail.
 ...
PMID:Amifostine and external beam radiation therapy and/or high-dose rate brachytherapy in the treatment of localized prostate carcinoma: preliminary results of a phase II trial. 1472 41

Tolerance of the normal rectal mucosa to radiation injury limits the dose that can be safely delivered to the prostate gland with definitive external beam radiation therapy. The radioprotective agent amifostine (Ethyol; MedImmune, Inc, Gaithersburg, MD) is approved for intravenous use. Laboratory studies indicate that rectal administration results in preferential accumulation of amifostine in the rectal mucosa, and in clinical studies, neither free parent compound nor free active metabolite has been detected in the systemic circulation. This trial evaluates the rates of early and late rectal toxicities in patients with prostate cancer receiving definitive or adjuvant three-dimensional conformal external beam radiation therapy and concurrent daily endorectal applications of amifostine. Endpoints include Radiation Therapy Oncology Group acute and late toxicity gradings, Expanded Prostate Cancer Index Composite self-assessment questionnaires, and proctoscopic examinations with scoring of mucosal damage measured before, during, and after treatment. Eleven patients have been enrolled to date; 10 have completed radiotherapy and three have been followed-up to 6 months. Two patients received 66 Gy to the prostatic bed post-prostatectomy; five patients received 74 Gy and three received 76 Gy to the prostate gland. In all patients, daily fractionation was 2 Gy, and 1 g of amifostine (50 mg/mL in 20 mL reconstituted saline) was administered endorectally 40 minutes before radiation delivery. Daily endorectal administration was well tolerated. To date, six patients have experienced grade 2 (Radiation Therapy Oncology Group) acute toxicities, all but one because of frequent bowel movements relieved by loperamide. The initial trial will proceed until 18 patients are accrued, at which time an interval evaluation of both early and late toxicity endpoints will be conducted.
 ...
PMID:Clinical trial of endorectal amifostine for radioprotection in patients with prostate cancer: rationale and early results. 1472 42

Pelvic malignancies, including bladder, prostate, and gynecologic cancers, are typically treated with some form of radiation therapy. Reducing radiation-related toxicities in these patients is important for maintaining good quality of life as survival rates increase and also for directly affecting cure rates by reducing delays in radiotherapy. Amifostine (Ethyol) has been shown to reduce rectal bleeding in patients with prostate cancer treated with radiation therapy, prevent radiation-related dermatitis, and provide widespread mucosal protection without adversely affecting local or distant tumor control.
 ...
PMID:Managing toxicities in pelvic malignancies. 1560 21