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Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer

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Abstract

Background

Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis, we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS).

Methods

All patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 and September 2017 were identified. The association between relative dose intensity (RDI) and OS was assessed using univariate and multivariable Cox model adjusting for age, Gleason score, burden of disease, visceral involvement, de novo metastases and baseline prostate-specific antigen (PSA).

Results

Eighty-one patients were included in the analysis. Only 35 patients (43%) were able to complete the planned treatment with a RDI of at least 90%. On a univariate analysis, higher RDI and number of cycles of docetaxel received were associated with longer OS. For every 10% decrease in RDI, the risk of death increased by 23% (HR 1.23, 95% CI 1.09–1.4, P = 0.001). For every increment of one cycle (and up to six), the risk of death decreased by 27% (HR 0.73, 95% CI 0.61–0.88, P = 0.001). On multivariate analysis, reduced RDI was the only predictor significantly associated with OS (HR 1.18, 95% CI 1.02–1.36, P = 0.026).

Conclusions

Our study suggests that in mCSPC, reduced docetaxel RDI is associated with shorter survival. Unnecessary dose reductions, treatment delays and early discontinuation should be avoided. Granulocyte colony-stimulating factor may be considered to maintain standard DI.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. The Ottawa Hospital Cancer Centre and University of Ottawa, Ottawa, ON, Canada

    Igal Kushnir, Michael Ong, Christina Canil, Dominick Bossé, Kim Koczka & Neil M. Reaume

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Igal Kushnir

  3. Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Ranjeeta Mallick

Authors
  1. Igal Kushnir
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  2. Ranjeeta Mallick
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  3. Michael Ong
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  4. Christina Canil
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  5. Dominick Bossé
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  6. Kim Koczka
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  7. Neil M. Reaume
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Correspondence to Igal Kushnir.

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Conflict of interest

IK declares a research grant from Astellas (unrelated to the current study). Stock ownership—Teva Pharmaceutical. Honoraria from Merck Sharp & Dohme (MSD), Bristol-Myers Squibb and Janssen. Consulting or advisory role from Merck Sharp & Dohme (MSD). MO declares honoraria from Jannsen and Astellas; Travel expenses from Jannsen. CC declares consulting or advisory role for Merck, EMD Serono, Pfizer, Novartis, Bayer, Bristol-Myers Squibb and Astra Zeneca; Honoraria from Janssen; Research funding (unrelated to the current study) from Eisai, Astellas, Janssen, Astra Zeneca and Roche; Travel expenses from Sanofi Grenzyme and Amgen. DB declares consulting or advisory role for Bristol-Myers Squibb (Inst), Pfizer, AbbVie; Honoraria from AstraZeneca, Ipsen, Amgen and Janssen. NMR declares consulting or advisory role for Astellas Pharma and Pfizer; Honoraria from AstraZeneca, Eisai, Ipsen, Merck, Novartis and Roche. RM and KK declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

For this retrospective study, formal consent was not required by the Ottawa Health Science Network Research Ethics Board.

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Kushnir, I., Mallick, R., Ong, M. et al. Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer. Cancer Chemother Pharmacol 85, 863–868 (2020). https://doi.org/10.1007/s00280-020-04063-7

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  • DOI: https://doi.org/10.1007/s00280-020-04063-7

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