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A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity
BACKGROUND: Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of do...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833204/ https://www.ncbi.nlm.nih.gov/pubmed/24136151 http://dx.doi.org/10.1038/bjc.2013.605 |
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author | Gibb, A Greystoke, A Ranson, M Linton, K Neeson, S Hampson, G Illidge, T Smith, E Dive, C Pettitt, A Lister, A Johnson, P Radford, J |
author_facet | Gibb, A Greystoke, A Ranson, M Linton, K Neeson, S Hampson, G Illidge, T Smith, E Dive, C Pettitt, A Lister, A Johnson, P Radford, J |
author_sort | Gibb, A |
collection | PubMed |
description | BACKGROUND: Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1–3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured. METHODS: Dose escalation of doxorubicin in cycles 1–3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m(–2)) with doxorubicin reduced to 25 mg m(–2) or omitted in cycles 4–6 to maintain cumulative exposure of 103–130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD. RESULTS: Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m(–2), so 45 mg m(–2) was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD. CONCLUSION: Escalated ABVD incorporating doxorubicin at 45 mg m(–2) in cycles 1–3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies. |
format | Online Article Text |
id | pubmed-3833204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-38332042014-11-12 A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity Gibb, A Greystoke, A Ranson, M Linton, K Neeson, S Hampson, G Illidge, T Smith, E Dive, C Pettitt, A Lister, A Johnson, P Radford, J Br J Cancer Clinical Study BACKGROUND: Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1–3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured. METHODS: Dose escalation of doxorubicin in cycles 1–3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m(–2)) with doxorubicin reduced to 25 mg m(–2) or omitted in cycles 4–6 to maintain cumulative exposure of 103–130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD. RESULTS: Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m(–2), so 45 mg m(–2) was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD. CONCLUSION: Escalated ABVD incorporating doxorubicin at 45 mg m(–2) in cycles 1–3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies. Nature Publishing Group 2013-11-12 2013-10-17 /pmc/articles/PMC3833204/ /pubmed/24136151 http://dx.doi.org/10.1038/bjc.2013.605 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Clinical Study Gibb, A Greystoke, A Ranson, M Linton, K Neeson, S Hampson, G Illidge, T Smith, E Dive, C Pettitt, A Lister, A Johnson, P Radford, J A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity |
title | A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity |
title_full | A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity |
title_fullStr | A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity |
title_full_unstemmed | A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity |
title_short | A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity |
title_sort | study to investigate dose escalation of doxorubicin in abvd chemotherapy for hodgkin lymphoma incorporating biomarkers of response and toxicity |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833204/ https://www.ncbi.nlm.nih.gov/pubmed/24136151 http://dx.doi.org/10.1038/bjc.2013.605 |
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