Does castration status affect docetaxel‐related adverse events? :Identification of risk factors for docetaxel‐related adverse events in metastatic prostate cancer

Abstract

Background Docetaxel‐related adverse events (AEs) such as neutropenia and febrile neutropenia (FN) can be life‐threatening. A previous in vivo study raised the hypothesis that the castration status affects the rate of hematologic AEs. We aimed to investigate the impact of castration status on the incidence of docetaxel‐related AE in metastatic prostate cancer (mPCa) patients. Methods We retrospectively analyzed the records of 265 mPCa patients treated with docetaxel, comprising 92 patients with metastatic hormone‐sensitive prostate cancer (mHSPC) and 173 patients with metastatic castration‐resistant prostate cancer (mCRPC) between January 2015 and December 2021. Common terminology Criteria for Adverse Events (CTCAE) was applied to evaluate AEs. We analyzed the differential incidences between mHSPC and mCRPC, and risk factors of hematologic and nonhematologic AEs using a logistic regression model. Results The rate of patients who received primary prophylaxis against neutropenia was higher in those with the mHSPC compared with those with the mCRPC (7.5% vs. 33%, p < 0.001). Among the patients without primary prophylaxis, incidence rates of severe neutropenia (CTCAE ≥ Grade3) and FN were 89% and 16% in patients with mCRPC compared to 81% and 18% in those with mHSPC. Logistic regression analysis revealed that age ≥ 75 years and failure to provide primary prophylaxis were independent risk factors of severe neutropenia (odds ratio [OR]: 2.39, 95% confidential interval [CI]: 1.10–5.18 and OR: 15.8, 95% CI: 7.23–34.6, respectively). Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) ≧ 1 was an independent risk factor of FN (OR: 2.26, 95% CI: 1.13–4.54). Castration status (mHSPC vs. mCRPC) was not associated with the risks of severe neutropenia and FN. Conclusions Castration status did not affect the risk of severe neutropenia or FN in mPCa patients treated with docetaxel regardless of the disease state. Failure to provide primary prophylaxis and advanced patient age are independent risk factors of severe neutropenia; while patients with poor PS are more likely to develop FN. These findings may help guide the clinical decision‐making for proper candidate selection of docetaxel treatment.

Comparative Study on the Effect of Docetaxel and Abiraterone in the Treatment of Metastatic Castration Resistant Prostate Cancer

“…At present, there are few clinical cases of targeted therapy for mCRPC. Some patients with mCRPC cell migration and invasion, so as to inhibit tumor growth and metastasis [11] . In addition, docetaxel may also rely on the regulation of tumor stem cells to inhibit tumor recurrence and drug resistance [12] .…”

Impact of disease volume on survival efficacy of triplet therapy for metastatic hormone-sensitive prostate cancer: a systematic review, meta-analysis, and network meta-analysis

“…A recent meta-analysis showed that ARSI-based doublet therapy had high probabilities for a net clinical benefit; however, docetaxel-based doublet as well as triplet therapy appeared unlikely to be beneficial [ 32 ]. Docetaxel is known to increase the risk of severe adverse events and can reduce the patient quality of life [ 2 , 33 ]. Our previous meta-analysis confirmed that docetaxel-based combination had a higher likelihood of severe adverse events, with triplet therapies being the highest adverse event rates [ 2 , 33 ].…”

“…Docetaxel is known to increase the risk of severe adverse events and can reduce the patient quality of life [ 2 , 33 ]. Our previous meta-analysis confirmed that docetaxel-based combination had a higher likelihood of severe adverse events, with triplet therapies being the highest adverse event rates [ 2 , 33 ]. In the subgroup analysis of the ARASENS trial, 74% of patients with low-volume disease who received triplet therapy experienced severe adverse events [ 8 ].…”

Efficacy of Systemic Treatment in Prostate Cancer Patients With Visceral Metastasis: A Systematic Review, Meta-analysis, and Network Meta-analysis

“…51 Of note, intensified therapy with DOC and/or ARSIs causes drug-specific AEs where DOC-related hematological AEs are sometimes life-threatening. 52 The goal of mHSPC management is to provide optimal outcomes by balancing the harm-to-benefit ratio. However, in this study, we did not assess the likelihood of AEs due to the lack of data stratified by visceral metastasis.…”