Seminars in radiation oncology
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Multicenter Study Clinical Trial
Intrarectal application of amifostine for the prevention of radiation-induced rectal injury.
Clinically symptomatic late injury to the rectal wall occurs in about one third of patients with prostate cancer treated with external beam irradiation. Reducing the physical dose to the anterior rectal wall without a similar reduction in the posterior peripheral zone is difficult because of the proximity of these structures. Based on our previous observations that intrarectal application of amifostine resulted in very high concentrations of amifostine and its active metabolite WR-1065 in the rectal wall of Copenhagen rats, the authors initiated a phase I clinical trial in 1998. ⋯ Rectal symptomatology after external beam radiotherapy to the pelvis cannot be assumed to reflect late radiation damage, because it often is a manifestation of an unrelated pathologic process. The preliminary efficacy data are encouraging and suggest that intrarectal administration of amifostine may reduce radiation damage. Further clinical studies are warranted.
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Randomized Controlled Trial Clinical Trial
Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II-III non-small cell lung cancer: preliminary results.
A prospective randomized study was conducted to determine whether amifostine (Ethyol) reduces the rate of severe esophagitis and hematologic and pulmonary toxicity associated with chemoradiation or improves control of non-small cell lung cancer (NSCLC). Sixty patients with inoperable stage II or III NSCLC were treated with concurrent chemoradiotherapy. Both groups received thoracic radiation therapy (TRT) with 1.2 Gy/fraction, 2 fraction per day, 5 days per week for a total dose 69.6 Gy. ⋯ Only 1 patient discontinued treatment because of hypotension. These preliminary results showed that amifostine significantly reduced acute severe esophagitis and pneumonitis. Further observation is required to assess long-term efficacy.
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Randomized Controlled Trial Clinical Trial
Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung cancer.
Radiotherapy (RT) or radiochemotherapy is the treatment of choice for patients with medically or technically inoperable non-small cell lung cancer (NSCLC) localized to the primary site and regional lymph nodes. Radiation-induced damage has been recognized as a major complication in thoracic RT. The use of concurrent chemoradiation has been associated with an increase in acute and late toxicity. ⋯ Complete or partial responses were achieved in 78% (18 of 23) of patients in the RT arm and 82% (18 of 22) in the A plus RT arm (P =.278). By week 5, 74% (17 of 23) of patients in the RT group versus 36% (8 of 22) in the A plus RT group experienced grade > or = 2 esophagitis. (During the follow-up period, pulmonary toxicity was evaluated by CT scan.) Three months after RT, 65% (15/23) of patients in the RT group and 32% (7 of 22) in the A plus RT group presented with grade > or = 2 pneumonitis (P =.038). Amifostine reduces the incidence of acute and late radiation-induced toxicities.
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Clinical Trial
Trade-off to low-grade toxicity with conformal radiation therapy for prostate cancer on Radiation Therapy Oncology Group 9406.
The aim of this study was to evaluate and compare the rates of grade 2 or worse late effects in patients treated for prostate cancer on Radiation Therapy Oncology Group (RTOG) 9406. The authors previously have reported the results of patients treated on the first 2 dose levels of this study with respect to grade 3 or greater late toxicity. This analysis examines the incidence of grade 2 toxicity in this study. ⋯ Because grade 2 late effects may have a significant impact on a patient's quality of life, it is important to reduce these complications as much as possible. Improved conformal treatment delivery with intensity-modulated radiation therapy or the use of radioprotective agents could be considered. Clinical trials should use quality-of-life measures to determine that trade-offs between severity and rates of toxicity are acceptable to patients.
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The effects of WR1065 (SH), the free thiol form of amifostine, on nuclear transcription factor kappaB (NFkappaB) activation, manganese superoxide dismutase (MnSOD) gene expression, and secretion of human vascular endothelial cell growth factor (hVEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, P-selectin, and interleukins IL-1alpha, IL-6, and IL-8 were investigated and compared in human microvascular endothelial (HMEC) and human glioma cells. WR1065 was evaluated at 2 concentrations, 4 mmol/L, ie, its most effective cytoprotective dose, and 40 micromol/L, a noncytoprotective but highly effective dose capable of preventing radiation and chemotherapeutic drug-induced mutations in exposed cells. A 30-minute exposure of HMEC and glioma cell lines U87 and U251 to WR1065 at either of the concentrations resulted in a marked activation of NFkappaB as determined by a gel shift assay, with the maximum effect observed between 30 minutes and 1 hour after treatment. ⋯ Gene expression was enhanced 1.8-fold over control levels in HMEC over a period ranging from 12 to 24 hours after the time of maximum activation of NFkappaB. In contrast, MnSOD gene expression in U87 cells rose 3.5 times above control levels over this same period. WR1065 had no effect on the levels of adhesion molecules, cytokines, and growth factors secreted by cells exposed for up to 24 hours as measured by enzyme-linked immunosorbent assay.