Intrarectal amifostine suspension may protect against acute proctitis during radiation therapy for prostate cancer: a pilot study.

PURPOSE: Our goal was to test the ability of intrarectal amifostine to limit symptoms of radiation proctitis. METHODS AND MATERIALS: The first 18 patients received 1 g of intrarectal amifostine suspension placed 30-45 min before each radiation treatment. The following 12 patients received 2 g of amifostine. Total dose prescribed ranged from 66 to 76 Gy. All patients were treated with three-dimensional conformal radiation therapy. The suspension remained intrarectal during treatment and was expelled after treatment. For gastrointestinal symptoms, during treatment and follow-up, all patients had a Radiation Therapy Oncology Group (RTOG) grade recorded. RESULTS: Median follow-up was 18 months (range, 6-24 months). With 2 g vs. 1 g amifostine, there was a nearly significant decrease in RTOG Grade 2 acute rectal toxicity. Seven weeks after the start of radiation therapy, the incidence of Grade 2 toxicity was 33% in the 1-g group (6/18) compared with 0% (0/12) in the 2-g group (p=0.06). No Grade 3 toxicity or greater occurred in this study. CONCLUSION: This trial suggests greater rectal radioprotection from acute effects with 2 g vs. 1 g amifostine suspension. Further studies should be conducted in populations at higher risk for developing symptomatic acute and late proctitis.

Comparing measures of acute bowel toxicity in patients with prostate cancer treated with external beam radiation therapy.

PURPOSE: This study strives to compare early measures of bowel toxicity in patients with prostate cancer receiving definitive or adjuvant 3D conformal external beam radiation therapy and concurrent daily endorectal application of amifostine. METHODS: Eighteen patients were enrolled in the clinical study with a median follow-up of 12 months. Prescription doses ranged from 66 Gy to 76 Gy with a daily fractionation of 2 Gy. Acute bowel toxicity was measured at baseline, at Weeks 5 and 7 of radiotherapy, and at 1 and 3 months after the completion of therapy. Measures of acute bowel toxicity included the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria, Expanded Prostate Cancer Index Composite (EPIC) self-assessment questionnaires, and proctoscopic examinations. RESULTS: The mean EPIC bowel scores changed significantly through the course of therapy and follow-up (p < 0.0001), with a progressive decrease in scores at Weeks 5 and 7 of treatment, a partial recovery at 3 months, and a correlation to the gold standard RTOG grade (p = 0.004). Proctoscopic toxicity scores were low, did not vary over time, and did not correlate with either EPIC or RTOG scores. CONCLUSION: The EPIC questionnaire measurements are most sensitive to changes in acute bowel toxicity through a course of radiotherapy and correlate with RTOG acute toxicity scores. Endoscopic examination of the rectal mucosa at the end and immediate follow-up of a course of therapy does not seem to be informative or reproducible between observers in the acute setting.

Early observed transient prostate-specific antigen elevations on a pilot study of external beam radiation therapy and fractionated MRI guided high dose rate brachytherapy boost.

PURPOSE: To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost. MATERIALS AND METHODS: Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml. RESULTS: Median follow-up was 24 months (range 18-36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6. CONCLUSION: We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive.