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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Prostate Cancer | Research

Activity and safety of KEES - an oral multi-drug chemo-hormonal metronomic combination regimen in metastatic castration-resistant prostate cancer

Authors: Mustafa Asowed, Nils O Elander, Linn Pettersson, Maria Ekholm, Dimitrios Papantoniou

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

Metastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge and evidence for late-line treatments in real-life is limited. The present study investigates the efficacy and safety of an oral metronomic chemo-hormonal regimen including cyclophosphamide, etoposide, estramustine, ketoconazole and prednisolone (KEES) administered in a consecutive biweekly schedule.

Methods

A retrospective cohort study in two Swedish regions was conducted. Overall (OS) and progression-free survival (PFS), biochemical response rate (bRR) and toxicities were analyzed.

Results

One hundred and twenty-three patients treated with KEES after initial treatment with at least a taxane or an androgen-receptor targeting agents (ARTA) were identified. Of those, 95 (77%) had received both agents and were the primary analysis population. Median (95% CI) OS and PFS in the pre-treated population were 12.3 (10.1–15.0) and 4.4 (3.8–5.5) months, respectively. Biochemical response, defined as ≥ 50% prostate-specific antigen (PSA) reduction, occurred in 26 patients (29%), and any PSA reduction in 59 (65%). PFS was independent of prior treatments used, and KEES seemed to be effective in late treatment lines. The bRR was higher compared to historical data of metronomic treatments in docetaxel and ARTA pre-treated populations. In multivariable analyses, performance status (PS) ≥ 2 and increasing alkaline phosphatase (ALP) predicted for worse OS. Nausea, fatigue, thromboembolic events and bone marrow suppression were the predominant toxicities.

Conclusions

KEES demonstrated meaningful efficacy in heavily pre-treated CRPC patients, especially those with PS 0–1 and lower baseline ALP, and had an acceptable toxicity profile.
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Metadata
Title
Activity and safety of KEES - an oral multi-drug chemo-hormonal metronomic combination regimen in metastatic castration-resistant prostate cancer
Authors
Mustafa Asowed
Nils O Elander
Linn Pettersson
Maria Ekholm
Dimitrios Papantoniou
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10780-y

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