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A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation
This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2001
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363753/ https://www.ncbi.nlm.nih.gov/pubmed/11161394 http://dx.doi.org/10.1054/bjoc.2000.1611 |
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author | Hartmann, J T Vangerow, A von Fels, L M Knop, S Stolte, H Kanz, L Bokemeyer, C |
author_facet | Hartmann, J T Vangerow, A von Fels, L M Knop, S Stolte, H Kanz, L Bokemeyer, C |
author_sort | Hartmann, J T |
collection | PubMed |
description | This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m(2) at day 1–3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m(2/)d over 18 h), ifosfamide (4 g/m(2)/d over 4 h) and etoposide (500 mg/m(2)/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 μg kg(−1) subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min(−1)) and 37% in the control patient group (107 to 67 ml min(−1)) (P< 0.01). Amifostine-treated patients revealed a less pronounced increase in albumine and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT(3)-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 μl(−1)) and thrombocytes (> 25 000 μl(−1))were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a shortened duration of hospital stay were observed in the amifostine arm. The reduction of acute toxicity observed in the amifostine arm resulted in 30% savings in costs for supportive care (Euro 4396 versus Euro 3153 per patient). Taking into account the drug costs of amifostine, calculation of in-patient treatment costs from the start of chemotherapy to discharge revealed additional costs of Euro 540 per patient in the amifostine arm. This randomized pilot study indicates that both organ and haematotoxicity of HD-VIC chemotherapy can be ameliorated by the use of amifostine. Additionally, a nearly complete preservation of GFR was observed in amifostine-treated patients which may be advantageous if repetitive cycles of HDCT are planned. Larger randomized trials evaluating amifostine cytoprotection during high-dose chemotherapy are warranted. © 2001 Cancer Research Campaign http://www.bjcancer.com |
format | Text |
id | pubmed-2363753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23637532009-09-10 A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation Hartmann, J T Vangerow, A von Fels, L M Knop, S Stolte, H Kanz, L Bokemeyer, C Br J Cancer Regular Article This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m(2) at day 1–3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m(2/)d over 18 h), ifosfamide (4 g/m(2)/d over 4 h) and etoposide (500 mg/m(2)/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 μg kg(−1) subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min(−1)) and 37% in the control patient group (107 to 67 ml min(−1)) (P< 0.01). Amifostine-treated patients revealed a less pronounced increase in albumine and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT(3)-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 μl(−1)) and thrombocytes (> 25 000 μl(−1))were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a shortened duration of hospital stay were observed in the amifostine arm. The reduction of acute toxicity observed in the amifostine arm resulted in 30% savings in costs for supportive care (Euro 4396 versus Euro 3153 per patient). Taking into account the drug costs of amifostine, calculation of in-patient treatment costs from the start of chemotherapy to discharge revealed additional costs of Euro 540 per patient in the amifostine arm. This randomized pilot study indicates that both organ and haematotoxicity of HD-VIC chemotherapy can be ameliorated by the use of amifostine. Additionally, a nearly complete preservation of GFR was observed in amifostine-treated patients which may be advantageous if repetitive cycles of HDCT are planned. Larger randomized trials evaluating amifostine cytoprotection during high-dose chemotherapy are warranted. © 2001 Cancer Research Campaign http://www.bjcancer.com Nature Publishing Group 2001-02 /pmc/articles/PMC2363753/ /pubmed/11161394 http://dx.doi.org/10.1054/bjoc.2000.1611 Text en Copyright © 2001 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Regular Article Hartmann, J T Vangerow, A von Fels, L M Knop, S Stolte, H Kanz, L Bokemeyer, C A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation |
title | A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation |
title_full | A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation |
title_fullStr | A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation |
title_full_unstemmed | A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation |
title_short | A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplanation |
title_sort | randomized trial of amifostine in patients with high-dose vic chemotherapy plus autologous blood stem cell transplanation |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363753/ https://www.ncbi.nlm.nih.gov/pubmed/11161394 http://dx.doi.org/10.1054/bjoc.2000.1611 |
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