-
Leukemia Research Dec 2000
Topics: Amifostine; Animals; Antineoplastic Agents; Apoptosis; Cell Survival; Humans; Leukemia, Myeloid; Mercaptoethylamines; Myeloid Progenitor Cells; Radiation-Protective Agents
PubMed: 11077114
DOI: 10.1016/s0145-2126(00)00081-3 -
American Journal of Clinical Oncology Jun 2011Fever/rash is a side-effect of amifostine that demands immediate interruption of the drug. Here, we focus on the role of C-reactive protein (CRP) as a putative marker...
INTRODUCTION
Fever/rash is a side-effect of amifostine that demands immediate interruption of the drug. Here, we focus on the role of C-reactive protein (CRP) as a putative marker linked with amifostine fever/rash.
MATERIALS AND METHODS
The CRP serum values were analyzed in 496 patients receiving radiotherapy supported with amifostine (500-1000 mg/d). CRP levels were recorded before the onset of radiotherapy (day 0), on day 15 and when the fever/rash appeared. For 121 out of 496 patients, CRP values on day 7 were also available. About 79 patients (15.9%) developed fever/rash symptoms.
RESULTS
The CRP levels before the onset of therapy were 0 to 20.7 mg/dL (normal, ≤0.5 mg/dL). For patients who did not develop fever/rash, the CRP levels increased from a median of 0.30 to 0.50 on day 15; P = 0.001. Patients who developed fever/rash showed a more than 7-fold increase of the median CRP levels (median, 3.50; P < 0.0001). This sharp CRP rise was specific for amifostine-related fever/rash. Initially abnormal CRP levels were linked with a 2-fold risk for fever/rash (P = 0.01), while abnormal levels on day 7 were linked with a 3-fold higher risk (P = 0.08). The occurrence of fever/rash was independent of the amifostine dose level.
CONCLUSIONS
Sharp rise of CRP levels on the day after the fever/rash development suggest amifostine-related etiology of fever/rash. Abnormal initial CRP levels and/or high CRP levels on day 7 should be considered as an alert signal as the probability to develop fever/rash reaches the 30%.
Topics: Adult; Aged; Amifostine; Biomarkers; C-Reactive Protein; Dose Fractionation, Radiation; Drug Administration Schedule; Drug Eruptions; Female; Fever; Humans; Male; Middle Aged; Predictive Value of Tests; Radiation-Protective Agents; Radiotherapy
PubMed: 20838325
DOI: 10.1097/COC.0b013e3181dea7bd -
Acta Oncologica (Stockholm, Sweden) 2003The purpose of this study was to investigate whether administration of amifostine prior to irradiation could reduce radiation damage of the rat heart. Female...
The purpose of this study was to investigate whether administration of amifostine prior to irradiation could reduce radiation damage of the rat heart. Female Spraque-Dawley rats were randomized to receive single-dose irradiation (0-22.5 Gy) locally to the heart. Fifteen to twenty minutes before radiation exposure, the animals received either intraperitoneally administered amifostine (160 mg/kg) or buffered saline solution. At 6 months post-irradiation, cardiac function was assessed by the in vitro working rat heart preparation. The severity of interstitial and/or perivascular fibrosis in different anatomical regions of the rat heart was assessed using a semi-quantitative scoring system. Radiation exposure to doses > or = 20 Gy markedly reduced coronary flow, aortic flow and cardiac output. Administration of amifostine prior to radiotherapy afforded protection against these effects and normal cardiac output was maintained, even after 22.5 Gy. A small, non-significant, reduction in histological damage (i.e. perivascular fibrosis and interstitial fibrosis) was also apparent in animals treated with amifostine. There was a clear protective effect of amifostine on the severity and extent of macroscopic damage in lung tissue included in the cardiac irradiation field. The findings of this study suggest that a single dose of amifostine administered prior to irradiation is effective in reducing cardiac damage.
Topics: Amifostine; Animals; Cardiac Output; Coronary Circulation; Drug Evaluation; Female; Fibrosis; Heart; Myocardium; Radiation-Protective Agents; Radiotherapy; Radiotherapy Dosage; Rats; Rats, Sprague-Dawley
PubMed: 12665324
DOI: 10.1080/0891060310002168 -
Seminars in Oncology Oct 1994The rationale for the clinical trials with amifostine (Ethyol, US Bioscience, Inc, West Conshohocken, PA) is based on an extensive body of preclinical data coming from... (Review)
Review
The rationale for the clinical trials with amifostine (Ethyol, US Bioscience, Inc, West Conshohocken, PA) is based on an extensive body of preclinical data coming from many laboratories around the world. Initial clinical trials centered on the hematotoxicity produced by cyclophosphamide, carboplatin, and cisplatin; hematotoxicities and mucosal toxicities from radiation therapy; and nephrotoxicity, neurotoxicity, and ototoxicity from cisplatin.
Topics: Amifostine; Antineoplastic Agents; Cell Survival; Clinical Trials as Topic; Female; Humans; Male; Neoplasms; Neutropenia; Ovarian Neoplasms; Radiation Injuries; Rectal Neoplasms
PubMed: 7973776
DOI: No ID Found -
Cancer Chemotherapy and Pharmacology Jan 2004The cytoprotective mechanism of amifostine (WR-2721) implies free radical scavenging and DNA repair activities. We investigated additional cytoprotective pathways...
PURPOSE
The cytoprotective mechanism of amifostine (WR-2721) implies free radical scavenging and DNA repair activities. We investigated additional cytoprotective pathways involving intracellular hypoxia and the activation of the hypoxia-inducible factor (HIF) pathway, a key transcription factor regulating glycolysis, angiogenesis and apoptosis, which is also linked with radioresistance.
MATERIALS AND METHODS
The glucose and oxygen levels in the peripheral blood of patients receiving 1000 mg amifostine were determined at various time-points in order to investigate the metabolic changes induced by amifostine. MDA468 breast tumor cell lines were incubated with a high amifostine concentration (10 m M) to overcome the natural resistance of cancer cells to influx of the non-hydrolyzed WR-2721, and the HIF1 alpha protein levels were determined by Western blot analysis. In vivo experiments with Wistar rats were performed in order to assess immunohistochemically changes in the intracellular accumulation of HIF1 alpha induced by amifostine (200 mg/kg).
RESULTS
By 30 min following amifostine administration, the hemoglobin oxygen saturation and pO(2) levels had increased in the peripheral blood while glucose levels had reduced, providing evidence that normal tissue metabolism switches to glycolytic pathways. Incubation of cell lines with amifostine resulted in HIF1 alpha induction. In Wistar rats administration of amifostine resulted in increased HIF1 alpha accumulation in normal tissues.
CONCLUSIONS
Since it is doubtful whether dephosphorylation of amifostine to the active metabolite WR-1065 occurs within tumoral tissues (an acidic environment that lacks vascular alkaline phosphatase activity), intracellular hypoxia and upregulation of HIF1 alpha represents an additional, normal tissue-specific, amifostine cytoprotective pathway.
Topics: Amifostine; Animals; Blood Glucose; Blotting, Western; Breast Neoplasms; Cell Hypoxia; Cell Line, Tumor; Cytoprotection; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Infusions, Intravenous; Kidney; Lung; Male; Radiation Dosage; Radiation-Protective Agents; Rats; Rats, Wistar; Transcription Factors; Up-Regulation
PubMed: 14574457
DOI: 10.1007/s00280-003-0691-z -
Seminars in Oncology Dec 2003Locoregional recurrence remains a major obstacle to achieving cure of locally advanced head and neck cancers despite maximal resection and postoperative external beam... (Review)
Review
Rationale for integrating high-dose rate intraoperative radiation (HDR-IORT) and postoperative external beam radiation with subcutaneous amifostine for the management of stage III/IV head and neck cancer.
Locoregional recurrence remains a major obstacle to achieving cure of locally advanced head and neck cancers despite maximal resection and postoperative external beam radiation therapy (EBRT). Locoregional failure occurs in 30% to 40% of high-risk resected head and neck cancer patients after standard postoperative EBRT. In an effort to overcome this problem, a number of strategies have been designed to enhance the effectiveness of radiation including concurrent postoperative chemoradiation, accelerated radiation schedules, incorporation of targeted biologic therapies, and improved radiation delivery techniques such as intensity modulated radiation and high-dose rate (HDR) intraoperative radiation therapy. Intraoperative radiation therapy (IORT) represents an important approach to improve outcome in head and neck cancer patients treated with definitive surgery. High-dose rate IORT is defined as the delivery of a single, large dose of radiation at the time of surgery when the tumor bed is exposed. In conjunction with EBRT, HDR-IORT offers several advantages including: (1) conformal delivery of a large dose of radiation while the tumor bed is precisely defined, minimizing the risk of a geographic miss; (2) potential for subsequent dose reduction of EBRT; (3) shortening overall treatment time; and (4) dose-escalation. Because mucositis represents the dose-limiting acute toxicity and xerostomia ranks as the most common long-term quality-of-life complaint, a reduction of the EBRT dose may provide an important benefit in reducing toxicity, especially when combined with the radioprotectant amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD). The purpose of this article is to review the rationale for integrating HDR-IORT with a reduced dose of postoperative EBRT combined with amifostine to improve locoregional control and quality of life outcomes in advanced-stage resected head and neck cancer patients.
Topics: Amifostine; Clinical Trials as Topic; Head and Neck Neoplasms; Humans; Intraoperative Period; Postoperative Period; Quality of Life; Radiation Injuries; Radiation-Protective Agents; Stomatitis; Xerostomia
PubMed: 14727239
DOI: 10.1053/j.seminoncol.2003.11.012 -
Duodecim; Laaketieteellinen... 1999
Review
Topics: Amifostine; Antineoplastic Agents; Clinical Trials as Topic; Humans; Neoplasms; Radiation-Protective Agents
PubMed: 11877841
DOI: No ID Found -
Annals of Plastic Surgery Aug 2016According to the American Society of Clinical Oncology, in 2012, more than 53,000 new cases of head and neck cancers (HNCs) were reported in the United States alone and...
According to the American Society of Clinical Oncology, in 2012, more than 53,000 new cases of head and neck cancers (HNCs) were reported in the United States alone and nearly 12,000 deaths occurred relating to HNC. Although radiotherapy (XRT) has increased survival, the adverse effects can be unrelenting and their management is rarely remedial. Current treatment dictates surgical mandibular reconstruction using free tissue transfer. These complex operations entail extended hospitalizations and attendant complications often lead to delays in initiation of adjuvant therapy, jeopardizing prognosis as well as quality of life. The creation of new bone by distraction osteogenesis (DO) generates a replacement of deficient tissue from local substrate and could have immense potential therapeutic ramifications. Radiotherapy drastically impairs bone healing, precluding its use as a reconstructive method for HNC. We posit that the deleterious effects of XRT on bone formation could be pharmacologically mitigated. To test this hypothesis, we used a rodent model of DO and treated with amifostine, a radioprotectant, to assuage the XRT-induced injury on new bone formation. Amifostine had a profound salutary effect on bone regeneration, allowing the successful implementation of DO as a reconstructive technique. The optimization of bone regeneration in the irradiated mandible has immense potential for translation from the bench to the bedside, providing improved therapeutic options for patients subjected to XRT.
Topics: Amifostine; Animals; Bone Regeneration; Male; Mandible; Osteogenesis, Distraction; Radiation Injuries; Radiation-Protective Agents; Radiotherapy; Random Allocation; Rats, Sprague-Dawley
PubMed: 27070667
DOI: 10.1097/SAP.0000000000000276 -
Human & Experimental Toxicology 2022This study aimed to elucidate the effects of amifostine (ethyol) (AM), a synthetic radioprotector, and red ginseng (RG), a natural radioprotective agent, against the...
This study aimed to elucidate the effects of amifostine (ethyol) (AM), a synthetic radioprotector, and red ginseng (RG), a natural radioprotective agent, against the toxic effect of ionizing radiation (IR) on kidney tissues through changes in biochemical and histopathological parameters in addition to contributions to the use of amifostine and RG in clinical studies Five groups were established: Group I (control, receiving only saline by gavage), Group II (IR only), and Group III (IR+AM, 200 mg/kg intraperitoneally (i.p.). Group IV (IR + RG, 200 mg/kg orally once a day for 4 weeks), and Group V (IR+RG+AM, 200 mg/kg orally once/day for 4 weeks before IR and 200 mg/kg AM administered (i.p.) 30 min before IR). All groups, except for the control group, were subject to 6-Gy whole-body IR in a single fraction. 24 h after irradiation, all animals were sacrificed under anesthesia. IR enhanced MDA, 8-OHdG, and caspase-3 expression while decreasing renal tissue GSH levels ( < .05). Significant numbers of necrotic tubules together with diffuse vacuolization in proximal and distal tubule epithelial cells were also observed. The examination also revealed substantial brush boundary loss in proximal tubules as well as relatively unusual glomerular structures. While GSH levels significantly increased in the AM, RG, and AM+RG groups, a decrease in KHDS, MDA, 8-OHdG, and caspase-3 expression was observed, compared to the group subject to IR only ( < .05). Therefore, reactive oxygen species-scavenging antioxidants may represent a promising treatment for avoiding kidney damage in patients receiving radiation.
Topics: Animals; Amifostine; Caspase 3; Kidney; Radiation, Ionizing; 8-Hydroxy-2'-Deoxyguanosine; Panax
PubMed: 36455263
DOI: 10.1177/09603271221143029 -
The Lancet. Oncology Jun 2003For many years, scientists have been investigating use of drugs to protect normal tissue from injury during radiation therapy, thereby increasing the amount of radiation...
For many years, scientists have been investigating use of drugs to protect normal tissue from injury during radiation therapy, thereby increasing the amount of radiation that can be safely administered to patients. Despite the introduction of modern shielding techniques, dose modulation, and tissue-volume mapping, a small amount of normal tissue surrounding the target volume is inevitably irradiated during treatment, which can lead to severe side-effects. The most recent chemical radioprotector to become available clinically is amifostine. On the basis of efficacy data from a phase III randomised trial in patients with head and neck cancer, which showed reduced acute and chronic xerostomia with preserved antitumour response, some institutions are now adding amifostine to their chemoradiation regimens. However, much controversy surrounds the use of this drug. Some investigators are worried that radioprotectors may stop tumour tissue responding to radiation and therefore reduce treatment effectiveness. Moreover, amifostine opponents argue that the evidence is insufficient to justify routine use of this drug. In this Debate, David Brizel, who worked on the phase III amifostine efficacy study, and Jens Overgaard, a vehement opponent of amifostine therapy, provide thought-provoking arguments for two opposing perspectives on this contentious issue.
Topics: Amifostine; Combined Modality Therapy; Humans; Neoplasms; Radiation Injuries; Radiation-Protective Agents
PubMed: 12788413
DOI: 10.1016/s1470-2045(03)01132-x