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Amifostine (WR-2721) is a cytoprotective agent that protects a broad range of normal tissues from the toxic effects of chemotherapy and radiotherapy without attenuating tumour response. This selective protection is due to the greater conversion and uptake of the active metabolite, WR-1065, in normal versus neoplastic tissues.
In a pivotal phase III trial, 242 patients with advanced ovarian cancer were randomised to receive treatment with cisplatin 100 mg/m2 and cyclophosphamide 1000 mg/m2 every 3 weeks with or without pretreatment with intravenous amifostine 910 mg/m2. Over 6 cycles of therapy, amifostine significantly reduced haematological, renal and neurological toxicities; treatment delays, treatment discontinuation and days in hospital related to these adverse events were also significantly reduced in patients receiving amifostine versus patients receiving chemotherapy alone.
In another randomised phase III trial in 303 patients with head and neck cancer undergoing irradiation therapy (total dose 50 to 70Gy), pretreatment with intravenous amifostine 200 mg/m2 significantly reduced the incidence of acute and late grade ≥2 xerostomia. However, mucositis was not significantly reduced in amifostine recipients compared with patients receiving radiotherapy alone, although this has been shown in smaller randomised trials.
Amifostine (340 mg/m2) also provided significant protection against pneumonitis and oesophagitis in patients with lung cancer receiving thoracic irradiation in a preliminary report from a phase III trial (n = 144). Other studies have demonstrated protective effects of amifostine in other tumour types and other chemotherapy, radiation and radiochemotherapy regimens; however, evidence is still limited in these indications. No evidence of tumour protection by amifostine has been demonstrated in any clinical trials.
Amifostine has also been shown to stimulate haematopoietic stem cells and has been investigated as a therapy for patients with myelodysplastic syndrome in number of small preliminary studies.
At the recommended dose and schedule, amifostine is generally well tolerated. Adverse effects are usually reversible and manageable and those most frequently experienced include nausea and vomiting, transient hypotension and somnolence and sneezing.
Conclusion: The results of phase III trials have confirmed the safety and efficacy of amifostine as a cytoprotectant to ameliorate cisplatin-induced cumulative renal toxicity, for which it is the only agent proven to be effective, and neutropenia in patients with advanced ovarian cancer, and to reduce xerostomia in patients with head and neck cancer receiving irradiation therapy. Depending on the outcome of numerous ongoing clinical trials, amifostine may eventually find broader clinical applications, both as a cytoprotectant and as a potential therapy in myelodysplastic syndrome.
Overview of Pharmacodynamic Properties
Amifostine is a prodrug which is converted by the membrane-bound enzyme alkaline phosphatase to the active metabolite WR-1065. WR-1065 is preferentially taken up into normal rather than neoplastic cells because of the higher alkaline phosphatase activity, better vascularisation and higher pH of normal tissue. Once inside the cell, WR-1065 protects against chemotherapy and radiotherapy damage by scavenging free radicals, donating hydrogen ions to free radicals, depleting oxygen and directly binding and inactivating cytotoxic drugs, thereby either avoiding or repairing DNA damage.
In preclinical studies, amifostine protected a broad range of normal tissues and organs from a variety of cytotoxic therapies including alkylating agents, platinum agents, anthracyclines, taxanes and irradiation. In most of these studies, amifostine did not reduce, and in specific instances actually enhanced, the cytotoxic effect of irradiation or chemotherapy on tumours. The best protective results were obtained when amifostine was given 5 to 30 minutes before cytotoxic therapy.
Recent investigations have shown that amifostine, in addition to its protective effects, may also exert a trophic effect on normal human haematopoietic progenitor cells. In 1 study, pretreatment with amifostine enhanced the formation of haematopoietic colonies by up to 7-fold in bone marrow taken from 6 healthy donors. Similar stimulatory effects have been observed in the bone marrow of patients with myelodysplastic syndrome.
Preclinical studies show that amifostine may protect against chemotherapyor radiotherapy-induced secondary tumours. In mice, pretreatment with amifostine (400 mg/kg intraperitoneally) was shown to reduce the formation of secondary tumours following treatment with gamma irradiation of the hind limbs. Preclinical studies have demonstrated that amifostine/WR-1065 can protect cells from the mutagenic effects of cisplatin, cyclophosphamide, bleomycin, chlormethine and irradiation at the hypoxanthineguanine phosphoribosyl transferase locus.
The antimutagenic effect of amifostine is observed at doses as low as 50 mg/kg in some animal models and can be seen when amifostine is administered either 30 minutes before or up to 3 hours after cytotoxic exposure.
Overview of Pharmacokinetic Properties
Following intravenous administration, amifostine is rapidly cleared from the plasma with a distribution half-life (t½α) of ≈0.8 minutes. The rapid clearance of amifostine is largely due to the fast conversion of amifostine to its active metabolite, WR-1065. This metabolite is also rapidly removed from the plasma (t½α of ≈11 minutes), probably because of rapid uptake into cells and conversion into disulphide metabolites.
Animal studies show that maximum tissue concentrations of WR-1065 occur rapidly, within 5 to 15 minutes after amifostine injection. Uptake of WR-1065 is greatest in kidney, salivary gland, intestinal mucosa, liver and lung tissue and is considerably lower in the brain and skeletal muscle.
Only small amounts of amifostine and its metabolites are excreted in the urine. In 10 patients receiving a 15-minute infusion of amifostine 740 mg/m2, the average percentage of the total administered amifostine dose in the urine was 1.05, 1.38 and 4.2% for amifostine, WR-1065 and WR-33278, respectively.
Some clinical and preclinical data suggest that amifostine exhibits nonlinear kinetics consistent with saturable metabolism. However, this remains to be determined.
Amifostine has undergone clinical evaluation as a cytoprotectant in patients receiving cytotoxic chemotherapy and/or irradiation therapy. In addition to this role, recent studies have investigated the ability of amifostine to stimulate haematopoietic stem cells in patients with myelodysplastic syndrome and as an adjunct therapy in patients undergoing autologous bone marrow transplant.
In most clinical trials, amifostine was administered as a short intravenous infusion of 740 or 910 mg/m2 before chemotherapy and ≤500 mg/m2 before irradiation therapy. There was no evidence of any tumour protection by amifostine in any comparative trials.
Doses of amifostine used in patients with myelodysplastic syndrome vary since an optimal schedule and dose have not yet been determined.
Chemoprotectant. Amifostine has been investigated in combination with a variety of different chemotherapy regimens in patients with a diverse range of solid and non-solid malignancies. The main focus of clinical investigation has been the efficacy of amifostine in protecting normal tissues from toxicities associated with platinum agents and cyclophosphamide. More recently, investigations into the use of amifostine in regimens containing other agents have been initiated.
In the largest study, a randomised phase III trial in 242 patients with advanced ovarian cancer, treatment with intravenous amifostine 910 mg/m2 before a regimen of cisplatin (100 mg/m2) and cyclophosphamide (1000 mg/m2) provided significant haematological, renal and neurological protection without affecting tumour response and patient survival. Over 6 cycles of therapy, the incidence of severe neutropenic episodes causing fever or requiring antibiotic therapy was significantly reduced in patients receiving amifostine versus patients receiving chemotherapy alone (10 vs 21%) which resulted in significantly fewer days in hospital (89 vs 226 days). By cycle 6, the percentage of patients requiring treatment delays or treatment discontinuation due to elevated serum creatinine levels was significantly lower in amifostine recipients (10 vs 36%), as was the percentage of patients whose creatinine clearance was reduced by ≥40% from baseline (13 vs 30%). The severity and incidence of peripheral neurotoxicity were also significantly reduced in amifostine recipients versus patients receiving cisplatin-based chemotherapy alone.
In other smaller comparative trials, amifostine was shown to protect against carboplatin- and mitomycin-induced thrombocytopenia and topotecan-induced neutropenia. However, amifostine did not seem to provide significant protection against the haematological or neurological toxicities of paclitaxel in 1 randomised trial. More data are necessary before the role of amifostine in combination with these various regimens can be determined.
The haematological protective effects of amifostine have been compared with those of the stimulatory effects of granulocyte colony-stimulating factor (G-CSF) in patients with non-small cell lung cancer (NSCLC) receiving carboplatin therapy. In this phase III trial, 45 patients were randomised to receive carboplatin [administered to achieve an area under the concentration-time curve (AUC) equal to 9] with either amifostine (n = 24; 740 mg/m2 given before and 2 hours after carboplatin) or G-CSF (n = 21; 263 μg/day for 13 days after carboplatin therapy). The results show that, while the 2 agents have comparable effects on neutropenia, amifostine is statistically superior to G-CSF in reducing thrombocytopenia and expediting platelet recovery.
In Patients Undergoing Bone Marrow Transplantation. In these patients, amifostine may reduce the nonhaematological adverse effects (e.g. mucositis) of high dose myeloablative carboplatin- or melphalan-based therapy and protect normal haematopoietic cells during ex vivo purging of autologous bone marrow. However, only limited data exist.
Radioprotectant. The radioprotective effects of amifostine have been analysed in patients receiving pelvic, thoracic, and head and neck irradiation in a number of comparative and noncomparative trials. Differences in the doses and regimens of amifostine and irradiation used, and different tumour types and efficacy parameters, make direct comparisons difficult.
In a randomised phase III study involving 303 patients with head and neck cancer receiving irradiation therapy (total dose 50 to 70Gy), pretreatment with amifostine 200 mg/m2 significantly reduced both acute and late xerostomia compared with irradiation alone. Amifostine did not reduce mucositis in this trial; however, amifostine has protected against mucositis in other, smaller comparative trials.
The protective effects of amifostine during thoracic irradiation were described in a preliminary report from a randomised phase III trial in 144 patients with lung cancer. In patients receiving pretreatment with amifostine 340 mg/m2 (n = 73), irradiation-induced oesophagitis and pneumonitis were significantly reduced compared with the control group (n = 71). Subcutaneous amifostine (500mg) also provided significant protection in a subgroup of 55 patients receiving thoracic irradiation therapy for a variety of thoracic tumours in another randomised trial.
The protective effect of amifostine in patients receiving pelvic irradiation has also been examined, although results are variable. Amifostine was shown to protect against late, but not early, mucosal toxicities in 1 randomised trial involving 71 patients with rectal adenocarcinoma. In another randomised trial involving a group of 36 patients with various pelvic tumours, amifostine was shown to protect against acute mucosal irradiation injury.
Radiochemotherapy Protectant. At this stage, there are only limited comparative data available from investigations of the role of amifostine as a cytoprotectant in patients receiving combined modality therapy.
In 1 randomised trial, amifostine was shown to provide significant protection against oesophagitis and pneumonitis in patients with NSCLC receiving chemotherapy with paclitaxel (60 mg/m2) or carboplatin (AUC = 2) in addition to thoracic irradiation therapy (2Gy daily for 5 days/week). However, in another larger randomised study in patients with NSCLC, amifostine did not provide significant haematological, renal or auditory protection against a regimen of cisplatin, ifosfamide and mitomycin combined with thoracic irradiation therapy.
Amifostine has also been evaluated in patients with head and neck cancer receiving combined irradiation and carboplatin therapy in 2 randomised trials. In both studies, amifostine pretreatment significantly reduced the incidence of severe mucositis and late xerostomia; amifostine also significantly reduced acute xerostomia and haematological toxicity in 1 study.
Therapeutic Potential in Myelodysplastic Syndrome. Investigations into the therapeutic potential of amifostine in patients with myelodysplastic syndrome are limited and only a few reports have been published in full. Because of the preliminary nature of these mainly noncomparative trials, a number of different amifostine regimens have been investigated in an effort to establish an optimal dosage and administration schedule. Response rates also vary widely, with uni- or multilineage haematological responses reported in 0 to 83% of patients.
The best results have been observed in patients receiving a treatment schedule of 3 times weekly amifostine 200 mg/m2 for 3 weeks followed by a 2-week break. The efficacy of this schedule has recently been shown in a randomised, double-blind, placebo-controlled study. Although these results have not been published in full, the response rate was 37% in patients receiving amifostine and 11% in patients receiving placebo. Amifostine has also been investigated in combination with other agents such as G-CSF, topotecan, pentoxifylline and dexamethasone with some success.
It is not yet known if the haematological effects of amifostine are sustained with prolonged treatment. In all the trials conducted to date, the haematopoietic effects of amifostine were transient, with cytopenias typically returning to baseline a few weeks after amifostine therapy was withdrawn.
At the recommended dose and schedule, amifostine is generally well tolerated. Adverse effects were usually reversible and manageable and those most frequently experienced include nausea and vomiting on the day of therapy and transient reductions in systolic blood pressure during infusion. Other adverse effects such as sneezing, somnolence, dizziness, flushing, hiccups and chills are generally episodic and do not require interruption of therapy.
Most authors report asymptomatic decreases in systolic blood pressure of between 20 and 50mm Hg with spontaneous normalisation of blood pressure usually occurring within 5 to 10 minutes after the infusion is stopped. In 2 large randomised trials, hypotension was reported in 61.5 and 15% of patients receiving intravenous amifostine 910 and 200 mg/m2 in addition to chemo- and radiotherapy, respectively. This adverse event rarely necessitates therapy withdrawal and blood pressure reductions observed to date have not been associated with central nervous system, cardiovascular or renal consequences.
Nausea and vomiting are usually mild to moderate in intensity and sudden in onset, occurring during or just after amifostine infusion and usually resolving spontaneously in less than an hour. These adverse effects can be reduced by administration of antiemetic agents such as dexamethasone and serotonin 5-HT3 receptor antagonists. In 2 large randomised trials, the incidence of nausea and vomiting was significantly higher in patients receiving amifostine in addition to chemotherapy or irradiation therapy than in patients receiving chemotherapy or irradiation therapy alone; however, in patients receiving chemotherapy, the incidence of severe (grade 3 or 4) nausea and vomiting was similar between patients treated with or without amifostine.
Transient decreases in serum calcium levels are occasionally observed in patients receiving amifostine therapy. However, clinically relevant hypocalcaemia is rare, occurring in <1% of patients. These effects can usually be mitigated with oral calcium and vitamin D supplements.
Allergic reactions, ranging from mild skin rashes to anaphylaxis, have rarely been reported with amifostine treatment.
Trials assessing the use of amifostine in young or elderly populations or in patients with myelodysplastic syndrome are limited at this stage but the drug appears to be well tolerated in these populations.
Pharmacoeconomic Aspects of Amifostine
The pharmacoeconomic aspects of using amifostine as a cytoprotectant in patients with ovarian cancer have been analysed in a US and a Canadian study.
The US study used a cost-utility analysis conducted from the perspective of the payer. Using the results from a large phase III, randomised clinical study, this trial analysed the impact of incorporating amifostine into a regimen of cyclophosphamide and cisplatin. The cost of amifostine therapy (6 cycles of 910 mg/m2) was estimated at 36 161 US dollars ($US) per quality-adjusted life-year saved (1997 costs), which falls within the range considered to be cost effective.
The Canadian study used willingness-to-pay methodology to estimate the amount that the Canadian tax-paying public would spend to make amifostine available to Canadians with ovarian cancer. From the responses obtained from 50 tax payers, the results indicated that tax payers would be willing to pay an average of 3476 Canadian dollars ($Can) [$US2451] (1997 costs) for amifostine as an income tax increase over their lifetime. When this amount was subtracted from the overall cost of amifostine ($Can3826; $US2697), the net cost of amifostine was $Can350 ($US247) per patient. If the dosage of amifostine is reduced from 910 to 740 mg/m2, the cost of amifostine is further reduced, resulting in a net benefit of $Can597 per patient.
The results of both these trials suggest that amifostine therapy should be in the range of affordable technologies in both the US and Canada.
In a preliminary report of an economic analysis in patients receiving amifostine in addition to cisplatin and irradiation therapy for head and neck cancer, amifostine appeared to provide cost savings due to the reduction in the adverse events of this regimen.
However, more detailed pharmacoeconomic analyses are necessary before the economic implications of incorporating amifostine into cancer treatment regimens can be confirmed.
Dosage and Administration
Amifostine is currently indicated to reduce the cumulative renal toxicity associated with cisplatin therapy in patients with advanced ovarian cancer or NSCLC, and to reduce acute and late xerostomia in patients with head and neck cancer receiving fractionated irradiation therapy where the irradiation port includes a substantial portion of the parotid glands. Amifostine is also approved for use in Europe to reduce the neutropenia-related risk of infection associated with combination therapy with cyclophosphamide and cisplatin in patients with advanced ovarian cancer.
The dosage of amifostine varies according to the accompanying treatment regimen. In patients receiving amifostine in addition to cisplatin, the recommended starting dose is 910 mg/m2 administered as a 15-minute intravenous infusion once daily, approximately 30 minutes before chemotherapy. When amifostine is given prior to radiotherapy, a dose of 200 mg/m2 is administered once daily as a 3-minute intravenous infusion 15 to 30 minutes before initiating standard fractionated irradiation therapy (1.8 to 2.0Gy).
Monitoring of blood pressure is necessary during infusion of amifostine, and infusion should be interrupted if there is a significant drop in systolic pressure (of ≥20mm Hg). The infusion may be restarted if blood pressure returns to baseline within 5 minutes and the patient remains asymptomatic. Amifostine 740 mg/m2 should be used for subsequent treatment cycles if the full dosage cannot be administered.
Amifostine therapy requires coadministration of an antiemetic and, if necessary, calcium supplementation. The efficacy and tolerability of amifostine has not been established in children or elderly patients, and the drug should be used with care in patients who have pre-existing cardiovascular or cerebrovascular disease or a history of stroke or transient ischaemic attacks.
- Spencer CM, Goa KL. Amifostine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as a radioprotector and cytotoxic chemoprotector. Drugs 1995 Dec; 50: 1001–31 CrossRef
- Capizzi RL. The preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies by amifostine. Semin Oncol 1999 Apr; 26 Suppl. 7: 3–21
- Grdina DJ, Kataoka Y, Murley JS. Amifostine: mechanisms of action underlying cytoprotection and chemoprevention. Drug Metabol Drug Interact 2000; 16(4): 237–79 CrossRef
- DeNeve WJ, Everett CK, Suminski JE, et al. Influence of WR2721 on DNA cross-linking by nitrogen mustard in normal mouse bone marrow and leukemia cells in vivo. Cancer Res 1988 Nov 1; 48: 6002–5
- Treskes M, van der Vigh WJF. WR2721 as a modulator of cisplatin- and carboplatin-induced side effects in comparison with other chemoprotective agents: a molecular approach. Cancer Chemother Pharmacol 1993 Nov; 33: 93–106 CrossRef
- Treskes M, Nijtmans LGJ, Fichtinger-Schepman AMJ, et al. Effects of the modulating agent WR2721 and its main metabolites on the formation and stability of cisplatin DNA adducts in vitro in comparison to the effects of thiosulphate and diethyldithiocarbamate. Biochem Pharmacol 1992 Mar 3; 43: 1013–9 CrossRef
- Romano MF, Lamberti A, Bisogni R, et al. Amifostine inhibits hematopoietic progenitor cell apoptosis by activating NF-κB/Rel transcription factors. Blood 1999 Dec 15; 94(12): 4060–6
- Ramakrishnan N, Catravas GN. N-(2-mercaptoethyl)-1,3-propanediamine (WR-1065) protects thymocytes from programmed cell death. J Immunol 1992 Mar 15; 148(6): 1817–21
- Provinciali M, Ciavattini A, Di Stefano G, et al. In vivo amifostine (WR-2721) prevents chemotherapy-induced apoptosis of peripheral blood lymphocytes from cancer patients. Life Sci 1999; 64: 1525–32 CrossRef
- Liu S-C, Murley JS, Woloschak G, et al. Repression of c-myc gene expression by the thiol and disulfide forms of the cytoprotector amifostine. Carcinogenesis 1997 Dec; 18: 2457–9 CrossRef
- Woloschak GE, Pauneski T, Chang-Liu CM, et al. Expression of thymidine kinase messenger RNA and a related transcript is modulated by radioprotector WR 1065. Cancer Res 1995 Nov 1; 55(21): 4788–92
- North S, El-Ghissassi F, Pluquet O, et al. The cytoprotective aminothiol WR1065 activates ?21 waf-1 and down regulates cell cycle progression through a p53-dependent pathway. Oncogene 2000 Feb 24; 19(9): 1206–14 CrossRef
- Murley JS, Grdina DJ. The effects of cycloheximide and WR-1065 on radiation-induced repair processes: a mechanism for chemoprevention. Carcinogenesis 1995 Nov; 16(11): 2699–705 CrossRef
- Calabro-Jones PM, Aguilera JA, Ward JF, et al. Uptake of WR-2721 derivatives by cells in culture: identification of the transported form of the drug. Cancer Res 1988 Jul 1; 48: 3634–40
- Kataoka Y, Murley JS, Patel R, et al. Cytoprotection by WR-1065, the active form of amifostine, is independent of p53 status in human malignant glioma cell lines. Int J Radiat Biol 2000 May; 76(5): 633–9 CrossRef
- Treskes M, Boven E, van de Loosdrecht AA, et al. Effects of the modulating agent WR2721 on myelotoxicity and antitumour activity in carboplatin-treated mice. Eur J Cancer A 1994; 30A(2): 183–7 CrossRef
- Wasserman TH, Phillips TL, Ross G, et al. Differential protection against cytotoxic chemotherapeutic effects on bone marrow CFUs by WR-2721. Cancer Clin Trials 1981; 4(1): 3–6
- Valeriote F, Tolen S. Protection and potentiation of nitrogen mustard cytotoxicity by WR-2721. Cancer Res 1982 Nov; 42(11): 4330–1
- Yuhas JM. Differential protection of normal tissue and malignant tissues against the cytotoxic effects of mechlorethamine. Cancer Treat Rep 1979 Jun; 63(6): 971–6
- Green D, Bensely D, Schein P. Preclinical evaluation of WR-151327: an orally active chemotherapy protector. Cancer Res 1994 Feb 1; 54: 738–41
- van Laar JA, van der Wilt CL, Treskes M, et al. Effect of WR-2721 on the toxicity and antitumor activity of the combination of carboplatin and 5-fluorouracil. Cancer Chemother Pharmacol 1992; 31: 97–102 CrossRef
- Millar JL, McElwain TJ, Clutterbuck RD, et al. The modification of melphalan toxicity in tumor bearing mice by S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR 2721). Am J Clin Oncol 1982 Jun; 5(3): 321–8 CrossRef
- Mollman JE, Glover DJ, Hogan WM, et al. Cisplatin neuropathy. Risk factors, prognosis, and protection by WR-2721. Cancer 1988 Jun 1; 61: 2192–5 CrossRef
- Kyoizumi S, McCune JM, Namikawa R. Direct evaluation of radiation damage in human hematopoietic progenitor cells in vivo. Radiat Res 1994 Jan; 137: 76–83 CrossRef
- Patchen ML, MacVittie TJ, Souza LM. Postirradiation treatment with granulocyte colony-stimulating factor and pre-irradiation WR-2721 administration synergize to enhance hemopoietic reconstitution and increase survival. Int J Radiat Oncol Biol Phys 1992; 22(4): 773–9 CrossRef
- Shpall EJ, Stemmer SM, Hami L, et al. Amifostine (WR-2721) shortens the engraftment period of 4-hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support. Blood 1994 Jun 1; 83: 3132–7
- Douay L, Hu C, Giarratana M-C, et al. Amifostine (WR-2721) protects normal haematopoietic stem cells against cyclophosphamide derivatives’ toxicity without compromising their antileukaemic effects. Eur J Cancer A 1995; 31A Suppl. 1: S14–6 CrossRef
- Douay L, Hu C, Giarratana M-C, et al. Amifostine improves the antileukemic therapeutic index of mafosfamide: implications for bone marrow purging [abstract]. Blood 1995; 86: 2849–55
- Pierelli L, Scambia G, Fattorossi A, et al. In vitro effect of amifostine on haematopoietic progenitors exposed to carboplatin and non-alkylating antineoplastic drugs: haemato-protection acts as a drug-specific progenitor rescue. Br J Cancer 1998 Oct; 78(8): 1024–9 CrossRef
- Taylor CW, Wang LM, List AF, et al. Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained. Eur J Cancer A 1997 Sep; 33: 1693–8 CrossRef
- List AF, Heaton R, Glinsmann-Gibson B, et al. Amifostine protects primitive hematopoietic progenitors against chemotherapy cytotoxicity. Semin Oncol 1996 Aug; 23 Suppl. 8: 58–63
- An J, Flomenberg N, Capizzi RL. Amifostine protects normal hematopoietic progenitors while sesitizing BCR/ABL+ myeloid leukemic progenitors to the cytotoxic effect of nitrogen mustard [abstract no. 2277]. Blood 1999; 94 Suppl. 1 (Pt 2)
- Meagher RC, Rothman SA, Paul P, et al. Purging of small cell lung cancer cells from human bone marrow using ethiofos (WR-2721) and light-activated merocyanine 540 phototreatment. Cancer Res 1989 Jul 1; 49: 3637–41
- Yuhas JM, Spellman JM, Jordan SW, et al. Treatment of tumours with the combination of WR-2721 and cisdichlorodiammineplatinum (II) or cyclophosphamide. Br J Cancer 1980; 42: 574–85 CrossRef
- Yuhas JM, Culo F. Selective inhibition of the nephrotoxicity of cis-dicholorodiammineplatinum(II) by WR-2721 without altering its antitumor properties. Cancer Treat Rep 1980 Jan; 64(1): 57–64
- Treskes M, Holwerda U, Nijtmans LGJ, et al. The reversal of cisplatin-protein interactions by the modulating agent WR2721 and its metabolites WR1065 and WR 33278. Cancer Chemother Pharmacol 1992 Apr; 29: 467–70 CrossRef
- Treskes M, Boven E, Holwerda V, et al. Time dependence of the selective modulation of cisplatin-induced nephrotoxicity by WR2721 in the mouse. Cancer Res 1992 Apr 15; 52: 2257–60
- Weichert-Jacobsen KJ, Bannowski A, Küppers F, et al. Direct amifostine effect on renal tubule cells in rats. Cancer Res 1999 Jul 15; 59: 3451–3
- Williams MV, Denekamp J. Modification of the radiation response of the mouse kidney by misonidazole and WR-2721. Int J Radiat Oncol Biol Phys 1983 Nov; 9: 1731–6 CrossRef
- Verstappen CC, Geldof AA, Postma TJ, et al. In vitro protection from cisplatin-induced neurotoxicity by amifostine and its metabolite WR 1065. J Neurooncol 1999 Aug; 44(1): 1–5 CrossRef
- Müller LJ, Moorer-van Delft CM, Treskes M, et al. Properties of WR2721 (Ethiofos) as modulator of cisplatin-induced neurotoxicity studied at the ultrastructural level in the pond snail Lymnaea-stagnalis. Int J Oncol 1993 Apr; 2: 701–10
- Dorr RT, Lagel K, McLean S. Cardioprotection of rat heart myocytes with amifostine (Ethyol) and its free thiol, WR-1065, in vitro. Eur J Cancer A 1996; 32A Suppl. 4: S21–5 CrossRef
- Nazeyrollas P, Prévost A, Baccard N, et al. Effects of amifostine on perfused isolated rat heart and on acute doxorubicin-induced cardiotoxicity. Cancer Chemother Pharmacol 1999 Mar; 43: 227–32 CrossRef
- Nici L, Calabresi P. Amifostine modulation of bleomycin-induced lung injury in rodents. Semin Oncol 1999 Apr; 26 Suppl. 7: 28–33
- Allalunis-Turner MJ, Siemann DW. Modification of cyclophosphamide-induced pulmonary toxicity in normal mice. NCI Monogr 1988; 6: 51–3
- Travis EL, De Luca AM. Protection of mouse lung by WR-2721 after fractionated doses of irradiation. Int J Radiat Oncol Biol Phys 1985 Mar; 11: 521–6 CrossRef
- Down JD, Laurent GJ, McAnulty RJ, et al. Oxygen-dependent protection of radiation lung damage in mice by WR 2721. Int J Radiat Biol Relat Stud Phys Chem Med1984 Nov; 46: 597–607 CrossRef
- Menard TW, Izutsu KT, Ensign WY, et al. Radioprotection by WR-2721 of gamma-irradiated rat parotid gland: effect on gland weight and secretion at 8–10 days post irradiation. Int J Radiat Oncol Biol Phys 1984 Sep; 10: 1555–9 CrossRef
- Sodicoff M, Conger AD, Trepper P, et al. Short-term radioprotective effects of WR-2721 on the rat paratoid glands. Radiat Res1978 Aug; 75(2): 317–26 CrossRef
- Sodicoff M, Conger AD, Pratt NE, et al. Radioprotection by WR-2721 against long-term chronic damage to the rat paratoid gland. Radiat Res1978 Oct; 76(1): 172–9 CrossRef
- Bohuslavizki KH, Klutmann S, Jenicke L, et al. Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit model. Int J Radiat Oncol Biol Phys 1999 Aug; 45(1): 181–6 CrossRef
- Dendale R, Bourhis J, Diawara O, et al. Effect of systemic and topical administration of amifostine on radiation-induced mucositis in mice [abstract]. 33rd Proc Am Soc Clin Oncol; 1997 May 17; 16: Denver (CO), 64a
- Capelli D, Santini G, De Souza C, et al. Amifostine can reduce mucosal damage after high-dose melphalan conditioning for peripheral blood progenitor cell autotransplant: a retrospective study. Br J Haematol2000; 110: 300–7 CrossRef
- Patriarca F. Amifostine pretreatment for protection against melphalan + busulfan-induced toxicity in high-dose therapy for multiple myeloma patients [abstract no. 5034]. Blood 1999; 94 Suppl. 1 (Pt 2): 404b
- Olivieri A, Poloni A, Capelli D, et al. Effect of amifostine on mucositis during autologous PBPC transplantation [abstract]. Blood 1998 Nov 15; 92 Suppl. 1 (Pt 1): 275
- De Souza CA, Santini G, Marino G, et al. Amifostine (WR-2721), a cytoprotective agent in high-dose cyclophosphamide treatment of non-Hodgkin’s lymphomas: a phase II study. Braz J Med Biol Res 2000; 33: 791–8 CrossRef
- Srivastava A, Nair SC, Srivastava VM, et al. Evaluation of unprotective efficacy of amifostine against cyclophosphamide induced hemorrhagic cystitis. Bone Marrow Transplant 1999 Mar; 23(5): 463–7 CrossRef
- Delaney JP, Bonsack ME, Felemovicius I. Radioprotection of the small rat intestine with topical WR-2721. Cancer 1994 Oct 15; 74: 2379–84 CrossRef
- Ito H, Meistrich ML, Barkley Jr HT, et al. Protection of acute and late radiation damage of the gastrointestinal tract by WR-2721. Int J Radiat Oncol Biol Phys 1986 Feb; 12: 211–9 CrossRef
- France Jr HG, Jirtle RL, Mansbach II CM. Intracolonic WR 2721 protection of the rat colon from acute radiation injury. Gastroenterology 1986 Sep; 91: 644–50
- Prasanna PGS, Devi PU. Modification of WR-2721 radiation protection from gastrointestinal injury and death in mice by 2-mercaptopropionylglycine. Radiat Res 1993 Jan; 133: 111–5 CrossRef
- Ito H, Komaki R, Milas L. Protection by WR-2721 against radiation plus cis-diamminedichloroplatinum II caused injury to colonic epithelium in mice. Int J Radiat Oncol Biol Phys 1994 Mar 1; 28: 899–903 CrossRef
- Wist EA. Effect of the radioprotector WR 2721 on the response of metastatic Lewis lung carcinoma colonies to alkylating agents. Acta Radiol Oncol 1985 May–Jun; 24: 259–62 CrossRef
- Milas L, Ito H, Hunter N. Effect of tumor size on S-2-(3-aminopropylamino)ethylphosphorothioic acid and misonidazole alteration of tumor response to cyclophosphamide. Cancer Res1983 Jul; 43: 3050–6
- Penhaligon M. Radioprotection of mouse skin vasculature and the RIF-1 fibrosarcoma by WR-2721. Int J Radiat Oncol Biol Phys 1984 Sep; 10: 1541–4 CrossRef
- Hunter NR, Guttenberger R, Milas L. Modification of radiation-induced carcinogenesis in mice by misonidazole and WR-2721. Int J Radiat Oncol Biol Phys 1992; 22(4): 795–8 CrossRef
- McChesney SL, Gillette EL, Dewhirst MW, et al. Influence of WR 2721 on radiation response of canine soft tissue sarcomas. Int J Radiat Oncol Biol Phys 1986 Nov; 12: 1957–63 CrossRef
- Milas L, Hunter N, Ito H, et al. Effect of tumor type, size, and endpoint on tumor radioprotection by WR-2721. Int J Radiat Oncol Biol Phys 1984 Jan; 10: 41–8 CrossRef
- Rasey JS, Krohn KA, Magee S, et al. Comparison of the protective effects of three phosphorothioate radioprotectors in the RIF-1 tumor. Radiat Res 1986 Nov; 108: 167–75 CrossRef
- Stewart FA, Rojas A, Denekamp J. Radioprotection of two mouse tumors by WR-2721 in single and fractionated treatments. Int J Radiat Oncol Biol Phys 1983 Apr; 9: 507–13 CrossRef
- Ribizzi I, Darnowski JW, Goulette FA, et al. Amifostine cytotoxicity and induction of apoptosis in a human myelodysplastic cell line. Leuk Res 2000 Jun; 24(6): 519–25 CrossRef
- Patchen ML, MacVittie TJ. Granulocyte colony-stimulating factor and amifostine (Ethyol) synergize to enhance hemopoietic reconstitution and increase survival in irradiated animals. Semin Oncol 1994 Oct; 21 Suppl. 11: 26–32
- List AF, Brasfield F, Heaton R, et al. Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome. Blood 1997 Nov 1; 90: 3364–9
- List AF, Talley M, Obregon Y, et al. Combined treatment with amifostine and topotecan: high remitting potential in advanced myelodysplastic syndrome (MDS) [abstract no. 103]. 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 28a
- Grossi A, Fabbri A, Santini V, et al. Amifostine in the treatment of low-risk myelodysplastic syndromes. Haematologica 2000 Apr; 85: 367–71
- Galanopoulos E, Kritikou-Griva J, Gligori J, et al. Treatment of myelodysplastic syndrome with amifostine and its effect on hematopoiesis [abstract no. 1367]. Blood 1999; 94 Suppl. 1 (Pt 1): 306a
- Milas L, Hunter N, Stephens LC, et al. Inhibition of radiation carcinogenesis in mice by S-2-(3-aminopropylamino)-ethylphosphorothioic acid. Cancer Res 1984 Dec; 44 (12 Pt 1): 5567–9
- Grdina DJ, Carnes BA, Grahn D, et al. Protection against late effects of radiation by S-2-(3-aminopropylamino)-ethylphosphorothioic acid. Cancer Res 1991 Aug 15; 51: 4125–30
- Carnes BA, Grdina DJ. In vivo protection by the aminothiol WR-2721 against neutron-induced carcinogenesis. Int J Radiat Biol 1992 May; 61: 567–76 CrossRef
- Grdina DJ, Peraino C, Carnes BA, et al. Protective effect of S-2-(3-aminopropylamino)ethylphosphorothioic acid against induction of altered hepatocyte foci in rats treated once with γ-radiation within one day after birth. Cancer Res 1985 Nov; 45 (11 Pt 1): 5379–81
- Hill CK, Nagy B, Peraino C, et al. 2-[(Aminopropyl)amino]ethanethiol (WR1065) is anti-neoplastic and anti-mutagenic when given during 60Co γ-ray irradiation. Carcinogenesis 1986; 7: 665–8 CrossRef
- Nagy B, Dale PJ, Grdina DJ. Protection against cis-diamminedichloroplatinum cytotoxicity and mutagenicity in V79 cells by 2-[(aminopropyl)amino ethanethiol. Cancer Res 1986 Mar; 46(3). 1132–1135
- Nagy B, Grdina DJ. Protective effects of 2-[(aminopropyl) amino]ethanethiol against bleomycin and nitrogen mustard-induced mutagenicity in V79 cells. Int J Radiat Oncol Biol Phys 1986 Aug; 12(8): 1475–8 CrossRef
- Kataoka Y, Perrin J, Hunter N, et al. Antimutagenic effects of amifostine: clinical implications. Semin Oncol 1996 Aug; 23 Suppl. 8: 53–7
- Grdina DJ, Kataoka Y, Basic I, et al. The radioprotector WR-2721 reduces neutron-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in mouse splenocytes when administered prior to or following irradiation. Carcinogenesis 1992 May; 13: 811–4 CrossRef
- Kataoka Y, Basic I, Perrin J, et al. Antimutagenic effects of radioprotector WR-2721 against fission-spectrum neutrons and 60Co γ-rays in mice. Int J Radiat Biol 1992 Mar; 61: 387–92 CrossRef
- Newton GL, Aguilera JA, Ward JF, et al. Binding of radioprotective thiols and disulfides in Chinese hamster V79 cell nuclei. Radiat Res 1996 Sep; 146(3): 298–305 CrossRef
- Grdina DJ, Shigematsu N, Dale P, et al. Thiol and disulfide metabolites of the radiation protector and potential chemo-preventive agent WR-2721 are linked to both its anti-cytotoxic and anti-mutagenic mechanisms of action. Carcinogenesis 1995 Apr; 16: 767–74 CrossRef
- Vaughan ATM, Grdina DJ, Meechan PJ, et al. Conformational changes in chromatin structure induced by the radioprotective aminothiol, WR-1065. Br J Cancer 1989 Dec; 60(6): 893–6 CrossRef
- Savoye C, Swenberg C, Hugot S, et al. Thiol WR-1065 and disulphide WR-33278, two metabolites of the drug ethyol (WR-2721), protect DNA against fast neutron-induced strand breakage. Int J Radiat Biol 1997 Feb; 71: 193–202 CrossRef
- Shaw LM, Bonner H, Lieberman R. Pharmacokinetic profile of amifostine. Semin Oncol 1996 Aug; 23 Suppl. 8: 18–22
- Shaw LM, Turrisi AT, Glover DJ, et al. Human pharmacokinetics of WR-2721. Int J Radiat Oncol Biol Phys 1986 Aug; 12: 1501–4 CrossRef
- Shaw LM, Glover D, Turrisi A, et al. Pharmacokinetics of WR-2721. Pharmacol Ther 1988; 39: 195–201 CrossRef
- Shaw L, Bonner H, Nakashima H, et al. Pharmacokinetics of amifostine in cancer patients: evidence for saturable metabolism [abstract]. Proc Am Soc Clin Oncol; 1994 Mar; 13: 144
- Shaw LM, Bonner HS, Schuchter L, et al. Pharmacokinetics of amifostine: effects of dose and method of administration. Semin Oncol 1999 Apr; 26 Suppl. 7: 34–6
- Korst AEC, Eeltink CM, Vermorken JB. Pharmacokinetics of amifostine and its metabolites in patients. Eur J Cancer A 1997 Aug; 33: 1425–9 CrossRef
- Utley JF, Seaver N, Newton GL, et al. Pharmacokinetics of WR-1065 in mouse tissue following treatment with WR-2721. Int J Radiat Oncol Biol Phys 1984 Sep; 10: 1525–8 CrossRef
- Shaw L, Brown W, Schein P, et al. A phase I study comparing the relative bioavailability of intravenous and subcutaneous administration of amifostine (Ethyol) [abstract]. 33rd Proc Am Soc Clin Oncol; 1997 May 17; 16: Dallas (TX), 250a
- Korst AEC, van der Sterre MLT, Gall HE, et al. Influence of amifostine on the pharmacokinetics of cisplatin in cancer patients. Clin Cancer Res 1998 Feb; 4: 331–6
- Korst AEC, van der Sterre MLT, Eeltink CM, et al. Pharmacokinetics of carboplatin with and without amifostine in patients with solid tumors. Clin Cancer Res 1997 May; 3: 697–703
- Schüller J, Czejka M, Krexner E, et al. Amifostine (AMI) differently influences pharmacokinetics (PK) of selected cystostatic agents (CY) [abstract]. Eur J Cancer A 1997 Sep; 33 Suppl. 8: S245 CrossRef
- Martens-Lobenhoffer J, Fuhlroth J, Ridwelski K. Influence of the administration of amifostine on the pharmacokinetics of 5-fluorouracil in patients with metastatic colorectal carcinoma. Int J Clin Pharmacol Ther 2000 Jan; 38: 41–4
- Eickhoff C, Eickhoff E, Regazzi M, et al. Influence of amifostine on the pharmacokinetics of anticancer drugs [abstract]. Pharm World Sci 2000 Feb; 22: A11
- Kletzl H, Czejka MJ, Schüller J, et al. In-vitro and in-vivo drug interaction between doxorubicin (DOXO), epirubicin (EPI) and the cytoprotective agent amifostine (AMI) [abstract]. 8th International Congress on Anticancer Treatment; 1998 Feb 3; Paris, 219
- Alza Pharmaceuticals. Ethyol (amifostine) for injection product information. Available from: URL: http://www.ethyol.com/pros/pi.htm [Accessed 2000 Dec 11]
- Kemp G, Rose P, Lurain J, et al. Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol 1996 Jul; 14: 2101–12
- Brizel DM, Wasserman TH, Henke M, et al. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol 2000 Oct 1; 18(19): 3339–45
- Antonadou D, Coliarakis N, Synodinou M, et al. Randomized phase III trial of radiation ± amifostine in patients with advanced stage lung cancer [abstract no. 18]. Int J Radiat Oncol Biol Phys 1999; 45 Suppl. 3: 154 CrossRef
- Souquet PJ, Fourniol A, Vergnenegre A, et al. Randomised phase III trial of MIP regimen (mitomycin-ifosfamide-platine) with or without amifostine (Ethyol) in advanced non-small cell lung cancer (NSCLC) [abstract no. 1882]. 35th Proc Am Soc Clin Oncol; 1999 May 15; 18: Atlanta (GA), 488a
- Avilés A, Díaz-Maqueo JC, Talavera A, et al. Bone marrow protection with amifostine in the treatment of high-risk malignant lymphoma. Eur J Cancer A 1997 Jul; 33: 1323–5 CrossRef
- Betticher DC, Anderson H, Ranson M, et al. Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study. Br J Cancer 1995 Dec; 72: 1551–5 CrossRef
- Budd GT, Ganapathi R, Adelstein DJ, et al. Randomized trial of carboplatin plus amifostine versus carboplatin alone in patients with advanced solid tumors. Cancer 1997 Sep 15; 80: 1134–40 CrossRef
- Glick JH, Glover D, Weiler C, et al. Phase I controlled trials of WR-2721 and cyclophosphamide. Int J Radiat Oncol Biol Phys 1984 Sep; 10: 1777–80 CrossRef
- Glover D, Glick JH, Weiler C, et al. WR-2721 protects against the hematologic toxicity of cyclophosphamide: a controlled phase II trial. J Clin Oncol 1986 Apr; 4: 584–8
- Hartmann JT, Jnop S, Fels LM, et al. The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors. Anticancer Drugs 2000 Jan; 11: 1–6 CrossRef
- Heidenreich A, Marx FJ, Peters HJ. Amifostine as protective agent in cisplatin-based chemotherapy of advanced bladder cancer. Urologe A 1999; 38(6): 586–91 CrossRef
- Johnson PWM, Muers MF, Peake MD, et al. A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer. Br J Cancer 2001; 84(1): 19–24 CrossRef
- Petrilli AS, Oliveira VC, Ginani R, et al. Amifostine (AM) in pediatric osteosarcoma (OS). 35th Proc Am Soc Clin Oncol; 1999 May 15; 18: Atlanta (GA), 560a
- Planting AST, Catimel G, de Mulder PHM, et al. Randomized study of a short course of weekly cisplatin with or without amifostine in advanced head and neck cancer. Ann Oncol 1999 Jun; 10: 693–700 CrossRef
- Fahlke J, Ridwelski K, Lippert H. High-dose therapy with combined 5-fluorouracil and folinic acid with and without amifostine in the treatment of patients with metastatic colorectal carcinoma. Int J Colorectal Dis 1999 Apr; 14: 128–30 CrossRef
- Gelmon K, Eisenhauer E, Bryce C, et al. Randomized phase II study of high-dose paclitaxel with or without amifostine in patients with metastatic breast cancer. J Clin Oncol 1999 Oct; 17: 3038–47
- Gold MA, Walker JL, Berek JS, et al. Amifostine pretreatment for protection against topotecan-induced hematologic toxicity: results of a multicenter phase II trial in patients with advanced gynecologic malignancies [abstract]. Gynecol Oncol 2000 Feb; 76: 279
- Jost LM, Michel G, Dunkel-de Raad S, et al. Value of amifostine-cytoprotection in cisplatin and fluorouracil (5-FU) chemotherapy in head and neck cancer (HNCA). A randomized open-label trial [abstract no. 1515]. 35th Proc Am Soc Clin Oncol; 1999 May 15; 18: Atlanta (GA), 392a
- Poplin EA, LoRusso P, Lokich JJ, et al. Randomized clinical trial of mitomycin-C with or without pretreatment with WR-2721 in patients with advanced colorectal cancer. Cancer Chemother Pharmacol 1994 Feb; 33: 415–9 CrossRef
- Stupp R, Priscoveanu A, Mingrone W, et al. Decreased toxicity and excellent tolerability, when amifostine is added to standard cisplatin and 5-fluorouracil chemotherapy for head and neck cancer. Schweiz Kerbs Bull 1999 Dec; 19: 166–9
- British Medical Association RPS of GB. Chapter 8: Malignant disease and immunosuppression (Side effects of cytotoxic drugs). British National Formulary, 2000. 39th ed. London: British Medical Association and the Royal Pharmaceutical Society of Great Britain, 2000: 389
- Rose PG. Amifostine cytoprotection with chemotherapy for advanced ovarian carcinoma. Semin Oncol 1996 Aug; 23 Suppl. 8: 83–9
- Anderson H, Mercer V, Thatcher N. A phase III randomised trial of carboplatin and amifostine versus carboplatin and G-CSF in patients with inoperable non-small cell lung cancer (NSCLC) [abstract]. 34th Proc Am Soc Clin Oncol; 1998 May 16; 17: Los Angeles (CA), 465a
- Cisplatin product summary. ABPI conpendium of data sheets and summaries of product characteristics; Datapharm Publications, 2000
- Oster W, Scheffler BS, Habboubi N, et al. Selective nephroprotection by ethyol (amifostine) from cumulative cisplatin toxicity [abstract]. Onkologie 1995 Oct; 18 Suppl. 2: 183 CrossRef
- Schiller JH, Storer B, Berlin J, et al. Amifostine, cisplatin, and vinblastine in metastatic non-small-cell lung cancer: a report of high response rates and prolonged survival. J Clin Oncol 1996 Jun; 14: 1913–21
- Di Paola RS, Schuchter L. Neurologic protection by amifostine. Semin Oncol 1999 Apr; 26 Suppl. 7: 82–8
- DiPaola R, Goodin S, Rodriguez R, et al. Amifostine and dose intense paclitaxel in patients with advanced malignancies [abstract]. 33rd Proc Am Soc Clin Oncol; 1997 May 17; 16: Denver (CO), 235a
- Mitchell RB, Campbell Jr WW. A phase II trial of amifostine to ameliorate the neurotoxicity of carboplatin/paclitaxel for advanced non-small cell lung cancer [abstract no. 2322]. 35th Proc Am Soc Clin Oncol; 1999 May 15; 18: Atlanta (GA), 601a
- Srimuninnimit V. A phase II study with carboplatin and paclitaxel plus amifostine in the treatment of advanced non-small cell lung cancer: preliminary report [abstract]. 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 524a
- Ndubisi BU, Guthrie TH, Benrubi GI, et al. A phase II open-label study to evaluate the use of amifostine (ethyol) in reversing chemotherapy-induced peripheral neuropathy (PN) in cancer patients: preliminary findings [abstract no. 2326]. 35th Proc Am Soc Clin Oncol; 1999 May 15; 18: Atlanta (GA), 602a
- Hartmann J, von Vangerow A, Fels LM, et al. A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation. Br J Cancer 2001; 84(3): 313–20 CrossRef
- Chauncey TR, Gooley TA, Lloid ME, et al. Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Am J Clin Oncol 2000 Aug; 23: 406–11 CrossRef
- Balzarotti M, Grisanti S, Granzow K, et al. Ex vivo manipulation of hematopoietic stem cells for transplantation: the potential role of amifostine. Semin Oncol 1999 Apr; 26 Suppl. 7: 66–71
- Cagnoni PJ, Jones RB, Bearman SI, et al. Use of amifostine in bone marrow purging. Semin Oncol 1996 Aug; 23 Suppl. 8: 44–8
- Rudat V, Meyer J, Momm F, et al. Protective effect of amifostine on dental health after radiotherapy of the head and neck. Int J Radiat Oncol Biol Phys 2000; 48(5): 1339–43 CrossRef
- Bohuslavizki KH, Klutmann S, Brenner W, et al. Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study. J Clin Oncol 1998 Nov; 16: 3542–9
- Bourhis J, De Crevoisier R, Abdulkarim B, et al. A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell cancer. Int J Radiat Oncol Biol Phys 2000; 46(5): 1105–8 CrossRef
- Koukourakis MI, Kyrias G, Kakolyris S, et al. Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized phase II study. J Clin Oncol 2000 Jun; 18: 2226–33
- Schönekäs KG, Wagner W, Prott FJ. Amifostine: a radioprotector in locally advanced head and neck tumors. Strahlenther Onkol 1999 Nov; 175 Suppl. 4: 27–9
- Liu T, Liu Y, He S, et al. Use of radiation with or without WR-2721 in advanced rectal cancer. Cancer 1992 Jun 1; 69: 2820–5 CrossRef
- Montana GS, Anscher MS, Mansbach IC, et al. Topical application of WR-2721 to prevent radiation-induced proctosigmoiditis: a phase I/II trial. Cancer 1992 Jun 1; 69: 2826–30 CrossRef
- Mabro M, Faivre S, Raymond E. A risk-benefit assessment of amifostine in cytoprotection. Drug Saf 1999 Nov; 21: 367–87 CrossRef
- Antonadou D, Pepelassi E, Synodinou M, et al. The prophylactic use of amifostine in the prevention of chemoradiation induced mucositis and xerostomia in head and neck cancer. Int J Radiat Oncol Biol Phys 1998; 42 Suppl. 1: 224 CrossRef
- Büntzel J, Schuth J, Küttner K, et al. Radiochemotherapy with amifostine cytoprotection for head and neck cancer. Support Care Cancer 1998 Mar; 6: 155–60 CrossRef
- Antonadou D, Synodinou M, Boufi M, et al. Amifostine reduces acute toxicity during radiochemotherapy in patients with localized advanced stage non small cell lung cancer [abstract no. 1960]. 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 501a
- Werner-Wasik M, Friedland D, Axelrod R, et al. Amifostine reduces severe esophagitis during concurrent chemotherapy with weekly paclitaxel and thoracic irradiation in patients with locally advanced non-small cell lung cancer [abstract no. 2267]. 35th Proc Am Soc Clin Oncol; 1999 May 15; 18: Atlanta (GA), 587a
- Tan W, Tin-U C, Zellars R, et al. Phase I study of weekly paclitaxel in combination with daily cisplatin and radiation in locally advanced head and neck (H/N), locally advanced non-small cell lung carcinoma (NSCL), and esophageal carcinoma [abstract no. 1582]. 35th Proc Am Soc Clin Oncol; 1999 May 15; 18: Atlanta (GA), 409a
- Rosen FR, Chung TD, Portugal B, et al. Amifostine (A), concomitant cisplatin (C), paclitaxel (P) and re-irradiation (RI) in recurrent head and neck cancer (HNC) [abstract no. 1686] 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 427a
- Amrein PC, Mclntyre J, Colevas AD, et al. A phase I trial of concurrent taxol and Bid radiotherapy with or without ethyol in patients with advanced squamous cell carcinoma of the head and neck [abstract no. 1651]. 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 418a
- Jaremtchuk V, Zarba JJ, Keropian M, et al. Phase I study of gemcitabine combined with radiotherapy with or without amifostine in patients with locally advanced head and neck cancer [abstract no. 1674]. 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 424a
- Yavuz AA, Aydin F, Yavuz NM, et al. A phase I trial of radiation therapy (RT) plus concurrent fixed dose amifostine (AMI) with escalating doses of twice-weekly gemcitabine (TW-GEM) in advanced pancreatic cancer [abstract no. 1105]. 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 283a
- Trog D, Bank P, Wendt TG, et al. Daily amifostine given concomitantly to chemoradiation in head and neck cancer: a pilot study. Strahlenther Onkol 1999; 175(9): 444–9 CrossRef
- Büntzel J, Glatzel M, Weinaug R, et al. Intensified radio-chemotherapy with amifostine in head and neck cancer [abstract]. Ann Oncol 1998; 9 Suppl. 4: 75–6
- Gaman G, Gaman A. Amifostine in the treatment of myelodysplastic syndrome [abstract]. Hematol J 2000 Jun; 1 Suppl. 1: 83
- Bowen DT, Denzlinger C, Brugger W, et al. Poor response rate to a continuous schedule of amifostine therapy for ‘low/intermediate risk’ myelodysplastic patients. Br J Haematol 1998 Dec; 103(3): 785–7 CrossRef
- Brasfield FM, Heaton R, Glinsmann-Gibson B, et al. Phase I/II trial of subcutaneous amifostine in patients with myelodysplastic syndrome (MDS) [abstract no. 13]. 34th Proc Am Soc Clin Oncol; 1998 May 16; 17: Los Angeles (CA), 4a
- deCastro CM, Gockerman JP, Moore JO, et al. Treatment of myelodysplastic syndrome with amifostine [abstract]. Blood 1998 Nov 15; Suppl. 1 (Pt 2): 251b
- Hofmann WK, Seipelt G, Ottmann OG, et al. Effect of treatment with amifostine used as a single agent in patients with refractory anemia on clinical outcome and serum tumor necrosis factor α levels. Ann Hematol 2000; 79: 255–8 CrossRef
- Kempin S, Sirott M, Cecchi G, et al. Phase II study of amifostine for the treatment of the myelodysplastic syndrome (MDS) [abstract no. 108]. 34th Proc Am Soc Clin Oncol; 1998 May 16; 17: Los Angeles (CA), 28a
- List AF, Holmes H, Greenberg PL, et al. Phase II study of amifostine in patients with myelodysplastic syndromes (MDS) [abstract no. 1362]. Blood 1999; 94 Suppl. 1 (Pt 2)
- Kagmakis P, Potamousi P, Mpisbiroula A, et al. The role of amifostine in myelodysplastic syndromes [abstract]. 9th International Congress on Anticancer Treatment; 1999 Feb 2: Paris, 249
- Raza A, Qawi H, Lisak L, et al. Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone. Blood 2000 Mar 1; 95: 1580–7
- Wadler S, Haynes H, Beitler JJ, et al. Management of hypocalcemic effects of WR2721 administered on a daily times five schedule with cisplatin and radiation therapy. J Clin Oncol 1993 Aug; 11: 1517–22
- Glover D, Riley L, Carmichael K, et al. Hypocalcemia and inhibition of parathyroid hormone secretion after administration of WR-2721 (a radioprotective and chemoprotective agent). N Engl J Med 1983 Nov 10; 309: 1137–41 CrossRef
- Turrisi AT, Glover DJ, Hurwitz S, et al. Final report of the phase I trial of single-dose WR-2721 [S-2-(3-aminopropylamino) ethylphosphorothioic acid]. Cancer Treat Rep 1986 Dec; 70: 1389–93
- Fouladi M, Koren G, Greenberg ML, et al. Safety and monitoring guidelines of amifostine in the pediatric population: results of a phase I/II trial of ICE with amifostine [abstract]. J Clin Pharmacol 1998 Sep; 38: 842
- Kavan P, Kabickova E, Stankova J, et al. Protection of normal tissue by amifostine (Ethyol) from the cytotoxic effects of megatherapy with autologous stem cell rescue in children [abstract]. Bone Marrow Transplant 1999 Mar; 23 Suppl. 1: 74
- Borst JD, Csáki C, Ferencz T, et al. Safety and efficacy of amifostine in children to prevent myelotoxicity of high-dose carboplatin: preliminary results of a cooperative phase I-II clinical trial [abstract]. 33rd Proc Am Soc Clin Oncol; 1997 May 17; 16: Denver (CO), 523a
- Adamson PC, Balis FM, Belasco JE, et al. A phase I trial of amifostine (WR-2721) and melphalan in children with refractory cancer. Cancer Res 1995 Sep 15; 55: 4069–72
- Spath-Schwalbe E, Lange C, Genvresse I, et al. The cytoprotective agent amifostine is well tolerated by patients ≥70 years [abstract no. 2428]. 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 617a
- Bennett CL, Golub R, Calhoun E, et al. Cost-utility assessment of amifostine in first-line therapy for ovarian cancer [abstract]. Int J Gynecol Cancer 1998; 8: 64–72
- Dranitsaris G. A pilot study to evaluate the feasibility of using willingness to pay as a measure of value in cancer supportive care: an assessment of amifostine cytoprotection. Support Care Cancer 1997 Nov; 5: 489–99 CrossRef
- Domagk KR, Werner E, Buntzel J, et al. Pharmacoeconomic study in patients with head and neck cancer (HNC) receiving radiochemotherapy [abstract]. 36th Proc Am Soc Clin Oncol; 2000 May 20; 19: New Orleans (LA), 441a
- Capizzi RL. Amifostine reduces the incidence of cumulative nephrotoxicity from cisplatin: laboratory and clinical aspects. Semin Oncol 1999 Apr; 26 Suppl. 7: 72–81
- Hensley ML, Schuchter LM, Lindley C, et al. American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. J Clin Oncol 1999 Oct; 17: 3333–55
- Alberts DS. Protection by amifostine of cyclophosphamide-induced myelosuppression. Semin Oncol 1999 Apr; 26 Suppl. 7: 37–40
- Berek JS, Bertelsen K, du Bois A, et al. Advanced epithelial ovarian cancer: 1998 consensus statements. Ann Oncol 1999; 10 Suppl. 1: S87–92 CrossRef
- Selvaggi G, Belani CP. Carboplatin and paclitaxel in non-small cell lung cancer: the role of amifostine. Semin Oncol 1999 Apr; 26 Suppl. 7: 51–60
- American Society of Clinical Oncology. Clinical practice guidelines for the treatment of unresectable non-small-cell lung cancer. J Clin Oncol 1997 Aug; 15(8): 2996–3018
- Alberts DS. Future directions in gynecologic cancer. Semin Oncol 1999 Apr; 26 Suppl. 7: 125–8
- Schiller JH. Future directions in non-small cell lung cancer. Semin Oncol 1999 Apr; 26 Suppl. 7: 120–4
- NCCN practice guidelines for the myelodysplastic syndromes. Oncology 1998 Nov; 12 (11A): 53–80
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