A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity.
Ranson, Malcolm R
Linton, Kim M
Neeson, Susan M
Illidge, Timothy M
Radford, John A
AffiliationDepartments of Medical and Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
MetadataShow full item record
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.
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 Cancer
JournalBritish Journal of Cancer
- Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study.
- Authors: Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM
- Issue date: 2013 Dec
- A phase II study of dose-dense and dose-intense ABVD (ABVDDD-DI ) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma.
- Authors: Russo F, Corazzelli G, Frigeri F, Capobianco G, Aloj L, Volzone F, De Chiara A, Bonelli A, Gatani T, Marcacci G, Donnarumma D, Becchimanzi C, de Lutio E, Ionna F, De Filippi R, Lastoria S, Pinto A
- Issue date: 2014 Jul
- Intensified treatment of patients with early stage, unfavourable Hodgkin lymphoma: long-term follow-up of a randomised, international phase 3 trial of the German Hodgkin Study Group (GHSG HD14).
- Authors: Gillessen S, Plütschow A, Fuchs M, Markova J, Greil R, Topp MS, Meissner J, Zijlstra JM, Eichenauer DA, Bröckelmann PJ, Diehl V, Borchmann P, Engert A, von Tresckow B
- Issue date: 2021 Apr
- Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial.
- Authors: Behringer K, Goergen H, Hitz F, Zijlstra JM, Greil R, Markova J, Sasse S, Fuchs M, Topp MS, Soekler M, Mathas S, Meissner J, Wilhelm M, Koch P, Lindemann HW, Schalk E, Semrau R, Kriz J, Vieler T, Bentz M, Lange E, Mahlberg R, Hassler A, Vogelhuber M, Hahn D, Mezger J, Krause SW, Skoetz N, Böll B, von Tresckow B, Diehl V, Hallek M, Borchmann P, Stein H, Eich H, Engert A, German Hodgkin Study Group., Swiss Group for Clinical Cancer Research., Arbeitsgemeinschaft Medikamentöse Tumortherapie.
- Issue date: 2015 Apr 11
- Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma.
- Authors: Skoetz N, Will A, Monsef I, Brillant C, Engert A, von Tresckow B
- Issue date: 2017 May 25