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 ≤ 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.
Subject(s)
Antineoplastic Agents/administration & dosage , Docetaxel/administration & dosage , Febrile Neutropenia/chemically induced , Prostatic Neoplasms, Castration-Resistant/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Docetaxel/adverse effects , Dose-Response Relationship, Drug , Humans , Male , Middle Aged , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Survival Rate , Treatment Outcome , Withholding TreatmentABSTRACT
Hepatic encephalopathy is an uncommon cause of neurologic deterioration associated with hyperammonemia, which results from hepatic dysfunction or altered ammonia metabolism. Often overlooked, hyperammonemia may occur via any of several pathophysiological processes, and in the setting of malignancy, it is a potentially reversible cause of confusion and coma. Hepatic dysfunction as a result of malignant infiltration, chemotherapeutic toxicities, targeted anticancer therapies, reactivation hepatitis, portosystemic shunting, and transarterial chemoembolization (TACE) is discussed, and an approach to etiological diagnosis and management is outlined.