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Neutropenic complications in the PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer

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journal contribution
posted on 2019-10-04, 10:38 authored by Antroula Papakonstantinou, Elham Hedayati, Mats Hellström, Hemming Johansson, Michael Gnant, Günther Steger, Richard Greil, Michael Untch, Volker Moebus, Sibylle Loibl, Theodoros Foukakis, Jonas Bergh, Alexios Matikas

Introduction: Myelosuppresion is a common side effect of chemotherapy and granulocyte-colony stimulating factor (G-CSF) is often used to reduce the risk of neutropenic events. The purpose of this exploratory analysis was to investigate neutropenic complications in the phase III PANTHER trial of standard 3-weekly chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide plus docetaxel (FEC/D) versus bi-weekly tailored dose-dense EC/D adjuvant chemotherapy in breast cancer.

Patients and methods: Febrile neutropenia, neutropenic infection and infection grade 3–4 according to CTC AE 3.0, were explored in relation to G-CSF use. Per cycle analysis was performed concerning dose reduction and dose delays in conjunction with G-CSF administration.

Results: In the experimental group, 98.9% of patients received primary G-CSF support during EC and 97.4% during docetaxel, compared with 49.7% during FEC and 63.88% during docetaxel in the standard group. Overall, the use of G-CSF was associated with a lower risk for developing neutropenic events (OR 0.44, 95% CI 0.35–0.55, p < .001). Chemotherapy delays due to neutropenia and leukopenia were significantly decreased among patients that received G-CSF (OR 0.098, 95% CI 0.06–0.15 and OR 0.32, 95% CI 0.18–0.58, respectively).

Discussion: In conclusion, G-CSF support reduces neutropenic events and permits increased relative dose intensity, which is essential for improved survival outcomes.

Funding

Alexios Matikas was supported by the Stockholm County Council (clinical postdoctorial appointment); Theodoros Foukakis is recipient of the Senior Clinical Investigator Award from the Swedish Cancer Society (grant number CAN 2017/1043). This study was supported by grants from the Swedish Cancer Society to the Karolinska Institutet, from the Swedish Breast Cancer Association (BRO), from the research funds at Radiumhemmets Forskningsfonder, and from Amgen, Roche, and Sanofi-Aventis to the Swedish Breast Cancer Group (SweBCG) at Karolinska University Hospital, the German Breast Group (GBG), and the Austrian Breast & Colorectal Cancer Study Group (ABCSG).

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