Comparative assessment of docetaxel for safety and efficacy between hormone-sensitive and castration-resistant metastatic prostate cancer

Urol Oncol. 2019 Dec;37(12):999-1005. doi: 10.1016/j.urolonc.2019.07.005. Epub 2019 Jul 31.

Abstract

Objective: To compare toxicity and response of docetaxel chemotherapy between metastatic hormone-sensitive prostate cancer (mHSPC) and castration-resistant metastatic prostate cancer (mCRPC) patients of the same therapeutic era for assessing of upfront docetaxel against the benchmark of docetaxel in the castrate resistant stage in the setting outside of clinical trials.

Methods: A prospectively collected database of real-world prostate cancer patients receiving docetaxel was divided in mHSPC and mCRPC cases and retrospectively analyzed. Principal objectives were toxicity measured by the common criteria of adverse events terminology and response characterized by Prostate specific antigen decline and radiographic progression-free disease at restaging. The prognostic value of suspected variables for grade 3 to 5 toxicity and response was investigated by logistic regression analysis.

Results: Of 72 patients 34 (47%) were treated for mHSPC and 38 (53%) for mCRPC. Patients with mCRPC were older and had worse performance status (P< 0.01). In mHSPC total number of grade 3 to 5 adverse events (24, median 0, interquartile range 0-1) was significantly less than in mCRPC (46, median 1, interquartile range 1-2) (P = 0.01). Multivariable analysis revealed age as independent predictive variable for grade 3 to 5 toxicity (P = 0.03) but not disease stage, Prostate specific antigen predocetaxel, volume of disease, and Eastern Cooperative Oncology Group performance status (P > 0.05). Objective response was significantly higher in mHSPC compared to mCRPC patients (P < 0.01). Multivariable analysis confirmed mHSPC stage as independent prognostic factor for radiographic progression free disease at restaging (P < 0.01).

Conclusions: The association of age with toxicity and of mHSPC stage with response resulted in significantly fewer grade 3 to 5 adverse events but higher response rates for upfront docetaxel in mHSPC compared with docetaxel in the later mCRPC stage.

Keywords: Castration-resistant; Chemohormonal therapy; Docetaxel; Hormone-sensitive; Metastatic; Prostate cancer.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Clinical Trials, Phase III as Topic
  • Disease Progression
  • Docetaxel / administration & dosage
  • Docetaxel / adverse effects*
  • Drug-Related Side Effects and Adverse Reactions / diagnosis*
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Humans
  • Kallikreins / blood
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Progression-Free Survival
  • Prospective Studies
  • Prostate / diagnostic imaging
  • Prostate / pathology
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Radiography
  • Retrospective Studies
  • Severity of Illness Index

Substances

  • Antineoplastic Agents
  • Docetaxel
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen