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dc.contributor.authorGibb, Adam
dc.contributor.authorGreystoke, Alastair
dc.contributor.authorRanson, Malcolm R
dc.contributor.authorLinton, Kim M
dc.contributor.authorNeeson, Susan M
dc.contributor.authorHampson, G
dc.contributor.authorIllidge, Timothy M
dc.contributor.authorSmith, Ed
dc.contributor.authorDive, Caroline
dc.contributor.authorPettitt, A
dc.contributor.authorLister, A
dc.contributor.authorJohnson, P
dc.contributor.authorRadford, John A
dc.date.accessioned2013-12-17T13:47:23Z
dc.date.available2013-12-17T13:47:23Z
dc.date.issued2013-11-12
dc.identifier.citationA study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity. 2013, 109 (10):2560-5 Br J Canceren
dc.identifier.issn1532-1827
dc.identifier.pmid24136151
dc.identifier.doi10.1038/bjc.2013.605
dc.identifier.urihttp://hdl.handle.net/10541/306964
dc.description.abstractBackground: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.
dc.language.isoenen
dc.rightsArchived with thanks to British journal of canceren
dc.titleA study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity.en
dc.typeArticleen
dc.contributor.departmentDepartments of Medical and Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren
html.description.abstractBackground: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.


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