Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amifostine (US Bioscience, West Conshohocken, PA; Ethyol, WR-2721), a phosphorylated thiol developed by the United States Army as a protective agent for military personnel in the event of nuclear warfare, has shown protection of normal tissues from the cytotoxic effects of therapeutic radiation and chemotherapy with preservation of cytotoxic effects on the tumor. The basis of this selective protection derives from the relatively rapid uptake and anabolism of Amifostine into normal tissues and minimal, slower uptake into tumor tissue. Preclinical investigations have demonstrated protection of bone marrow stem cells from the toxic effects of radiation and chemotherapy. Several controlled clinical trials demonstrated this hematoprotective effect. In patients given 1.5 g/m2 cyclophosphamide and month later given Amifostine (740 mg/m2) followed by the same dose of cyclophosphamide, the median nadir neutrophil count was significantly increased and duration of neutropenia was significantly reduced by pretreatment with Amifostine. In women with stage III/IV ovarian cancer treated with 1 g/m2 cyclophosphamide and 100 mg/m2 cisplatin +/- Amifostine 910 mg/m2, treatment with Amifostine before cyclophosphamide and cisplatin resulted in a significant decrease in both the incidence and duration of hospital stays for neutropenic fever compared to cyclophosphamide and cisplatin alone. There were equivalent rates of response and duration of survival in both groups. Other studies have shown Amifostine protects bone marrow purged in vitro with 4-hydroperoxycyclophosphamide before autologous bone marrow transplantation. This preservation of marrow stem cells resulted in a statistically significant decrease in time to marrow engraftment, need for platelet transfusions and antibiotics, and duration of hospital stay. Amifostine-mediated protection of normal bone marrow illustrated in preclinical experiments is also evident in clinical trials. Amifostine preserves trilineage stem cells (red blood cells, platelets, and white blood cells) in contrast to the lineage-specific effects of the colony-stimulating factors. Theoretically, Amifostine and the colony-stimulating factors should provide complementary benefits to bone marrow recovery and function after cytotoxic therapies. These observations offer the promise of using high doses of chemotherapy to exploit antitumor, dose-response relationships in clinical trials.
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PMID:Amifostine-mediated protection of normal bone marrow from cytotoxic chemotherapy. 824 82

The first report on the administration of the chemoprotective agent Ethyol (amifostine) in conjunction with high dose carboplatin to a patient in the pediatric/adolescent age group is presented. A 17 year old teenager with recurrent cerebellar medulloblastoma received a total of five courses of high dose carboplatin 2 x 600 mg/m2 (1200 mg/m2 total) in each cycle. A complete response has been observed following the third treatment cycle. However, cumulative grade IV hematological toxicity developed following each of the first four treatments. Therefore, the fifth treatment was administered in conjunction with amifostine, at a dose of 2 x 740 mg/m2. Time to complete hematological recovery (Hb > 100 g/l, granulocytes > 2.0 G/l, platelets > 100 G/l) was 52, 58, 72, 78 and 50 days, respectively, following treatments nos 1, 2,,3, 4 and 5. The duration of grade III-IV neutropenia (< 1.0 G/l) was 3, 7, 8, 10 and 5 days, respectively. The duration of grade II-IV thrombocytopenia (platelets < 75 G/l) was 10, 25, 35, 40 and 32 days, respectively. Grade IV thrombocytopenia (platelets < 25 G/l) lasted for 5, 10, 12, 18 and 3 days, respectively, after each consecutive treatment. The total number of platelet transfusions was 1, 2, 2, 3 and 1, with the transfusion of 6, 9, 11, 11 and 5 units of platelets. The administration of amifostine has not been accompanied by any serious side effect. A short decrease in body temperature and a transient drop of blood pressure have been observed. Although hematological toxicity of high dose carboplatin has not been eliminated by amifostine, we conclude that significant protection was achieved in this situation of progressive bone marrow exhaustion.
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PMID:Administration of Ethyol (amifostine) to a child with medulloblastoma to ameliorate hematological toxicity of high dose carboplatin. 874 9

Physicians are frequently pressured to make therapeutic decisions within a cost-effective framework to demonstrate value to managed care. Because cancer is a chronic disease, health care costs are known to be expensive and physicians must use their resources as efficiently as possible. Historically, economic analyses in oncology have emphasized survival as their clinical end point. Today, both government groups and professional organizations are moving toward making quality of life the clinical end point in determining the economics of chemotherapy. This report evaluates the cost and efficacy of amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) use in the treatment of advanced ovarian cancer using two pharmacoeconomic analyses. A cost-utility analysis performed in the United States indicated that inclusion of amifostine therapy had both a favorable clinical and cost-utility profile compared with other medical therapies. A second cost-benefit analysis, conducted in Canada, suggested that use of amifostine in patients with advanced ovarian cancer would be cost saving. Amifostine is a novel agent that protects against both chemotherapy- and radiotherapy-induced toxicities, such as nephrotoxicity, neutropenia, thrombocytopenia, peripheral neuropathy, mucositis, and xerostomia. These toxicities are disturbing to both patients and physicians alike. The results of these studies support the use of amifostine as a valuable resource both economically and clinically.
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PMID:Pharmacoeconomics of amifostine in ovarian cancer. 1034 68

Concurrent chemotherapy and radiation has improved the outcome for patients presenting with locally advanced squamous cell carcinomas of the head and neck (SCCHN). These improvements have come at a cost of increased treatment-related toxicities. We previously reported the results of a phase II trial examining the role of concurrent carboplatin, paclitaxel, and daily radiotherapy (RT) in SCCHN. In an attempt to decrease these side effects, we conducted a prospective phase II trial evaluating the role of amifostine (Ethyol, MedImmune Oncology, Inc, Gaithersburg, MD) in patients treated with this concurrent chemoRT scheme. From April 2002 to September 2004, 19 patients with stage III-IV SCCHN were enrolled on a prospective phase II trial. Treatment consisted of daily RT delivered to 70.2 Gy (1.8 Gy/fx) with amifostine 500 mg IV (<1 hour before RT), and concurrent weekly carboplatin (100 mg/m2) and paclitaxel (40 mg/m2). Median age was 58.5 years (range, 48 to 70 years); male to female ratio was, 83%:17%; Caucasian versus other was, 61%/39%. Tumor characteristics based on histology were: primary cancers of the oropharynx (55.6%); supraglottic larynx (16.7%); hypopharynx (16.7%); oral cavity (5.6%); and unknown primaries (5.6%). All patients presented with locally advanced, unresectable disease T4 (50%), T3 (27.8%), and advanced nodal disease (N2b-N3) (78%). Toxicities were measured weekly during treatment and at each follow-up visit. Disease response to therapy was determined 2 months after completion of therapy. Seventeen patients are evaluable for response and survival at 2 months following completion of RT. Eighty-four percent completed the prescribed radiation treatment, and 84% of patients received more than six cycles of chemotherapy. The median number of missed chemotherapy cycles was 1.5 (range, 0 to 5 cycles). Fifty-six percent of patients received more than 90% of prescribed amifostine doses, with chemoRT-related toxicity being the most common reason for withholding the dose (77%). Median doses of missed amifostine were three (range, 0 to 30 doses). Grade 3 toxicities associated with therapy were: mucositis and dysphagia (40% of patients each), dehydration (27%), xerostomia (20%), and dermatitis (20%); 53% of patients experienced grade 3 leukopenia, while grade 3/4 neutropenia developed in 20%/13%. No grade 4/5 nonhematologic toxicities were encountered. Forty percent of patients completed RT without unscheduled treatment breaks secondary to treatment-related toxicity. Median treatment-break time was 5 days (range, 0 to 20 days). Clinical complete response at both the primary site of disease and neck was achieved in 75% of patients 2 months following completion of RT. Weekly carboplatin and paclitaxel administered concurrently with definitive RT and daily amifostine is well tolerated, with over 85% of patients completing therapy with acceptable toxicity. The addition of amifostine appears to decrease treatment-related toxicity without impacting efficacy.
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PMID:The evaluation of amifostine for mucosal protection in patients with advanced loco-regional squamous cell carcinomas of the head and neck (SCCHN) treated with concurrent weekly carboplatin, paclitaxel, and daily radiotherapy (RT). 1572 15