Risk of febrile neutropenia and early treatment cessation in men receiving standard and dose-reduced 3-weekly docetaxel for metastatic castration-resistant prostate cancer

Anis A Hamid; Kaspar Willson; Andrew D Vincent; Babak Tamjid; Margaret Lee; Alice Bergin; Chun Gan; Ainsley Campbell; Josephine Stewart; Carmel Pezaro; Ben Tran; Andrew J Weickhardt

doi:10.1111/ajco.12840

Risk of febrile neutropenia and early treatment cessation in men receiving standard and dose-reduced 3-weekly docetaxel for metastatic castration-resistant prostate cancer

Asia Pac J Clin Oncol. 2018 Oct;14(5):e399-e404. doi: 10.1111/ajco.12840. Epub 2018 Jan 10.

Authors

Affiliations

¹ Olivia Newton-John Cancer Wellness and Research Center, Austin Hospital, Heidelberg, Victoria, Australia.
² Freemasons Foundation Center for Men's Health, Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
³ Eastern Health and Monash University Eastern Health Clinical School, Box Hill, Victoria, Australia.
⁴ Epworth Freemasons, East Melbourne, Victoria, Australia.
⁵ Royal Melbourne Hospital, Parkville, Victoria, Australia.
⁶ Peter MacCallum Cancer Center, Victorian Comprehensive Cancer Center, Parkville, Victoria, Australia.

PMID: 29318740
DOI: 10.1111/ajco.12840

Abstract

Background: Docetaxel is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC); however, many patients experience febrile neutropenia (FN) and cease treatment early due to toxicity. It is not known whether lower dose (LD) q3-weekly docetaxel impacts toxicity or efficacy.

Methods: Multicenter retrospective study included 166 patients with mCRPC who received q3-weekly docetaxel between 2010 and 2015. Demographic, disease, chemotherapy (standard dose, SD $>$ 60 mg/m² vs LD $\leq$ 60 mg/m² ) and toxicity data were collected. Univariable and multivariable logistic and competing risk regression models evaluated docetaxel-dose association with FN and early treatment cessation (ETC) due to toxicity. Associations between dose and efficacy end points were also evaluated. Analyses were repeated employing inverse propensity score weights.

Results: Patients who received LD docetaxel (28.9%) were older with poorer Eastern Cooperative Oncology Group (ECOG) status. Fifteen percent of patients experienced FN, with a nonsignificant trend to lower incidence in the LD group (multiple adjusted odds ratio [OR] = 0.42; P = 0.21). Neither baseline patient nor prior treatment factors were predictive of FN. ETC due to toxicity occurred in 35%, with risk associated with increasing age, comorbidity count and poorer ECOG. There was no difference between LD and SD with respect to ETC due to toxicity, in unweighted and weighted analyses (LD vs SD, multivariable weighted hazard ratio [HR] = 1.47; P = 0.08). LD was associated with reduced prostate-specific antigen (PSA) response (50% vs 66.1%, multivariable weighted HR = 0.54; P = 0.03) and overall survival (median 7.9 vs 13.8 months, multivariable weighted HR = 2.19; P < 0.0001).

Conclusions: LD docetaxel for mCRPC did not mitigate the risk of FN or ETC due to toxicity. Dose reduction may result in poorer PSA response and survival.

Keywords: castration resistant; chemotherapy toxicity; docetaxel; febrile neutropenia; metastatic prostate cancer.

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Agents / administration & dosage*
Antineoplastic Agents / adverse effects
Docetaxel / administration & dosage*
Docetaxel / adverse effects
Dose-Response Relationship, Drug
Febrile Neutropenia / chemically induced*
Humans
Male
Middle Aged
Prostate-Specific Antigen
Prostatic Neoplasms, Castration-Resistant / drug therapy*
Prostatic Neoplasms, Castration-Resistant / pathology
Retrospective Studies
Survival Rate
Treatment Outcome
Withholding Treatment

Substances

Antineoplastic Agents
Docetaxel
Prostate-Specific Antigen