Predictors of Chemotherapy-Induced Toxicity and Treatment Outcomes in Elderly Versus Younger Patients With Metastatic Castration-Resistant Prostate Cancer.
In the present study, we examined possible predictors of chemotherapy-induced toxicity, treatment outcomes, and the consequences of dose reductions in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving standard docetaxel.



Medical records from 421 consecutive patients treated with first-line docetaxel (75 mg/m2every 3 weeks) and low-dose prednisolone from 2007 to 2013 at Herlev University Hospital were reviewed. Common Terminology Criteria for Adverse Events, version 4.0, and the Prostate Cancer Working Group 2 guidelines were used to evaluate treatment-related toxicity and efficacy. Logistic and Cox regression models were used to predict toxicity and survival.



Age ≥ 75 years (odds ratio [OR], 2.33), baseline levels of hemoglobin (OR, 0.89), and previous metastatic epidural spinal cord compression (MESCC; OR, 1.70) were predictive of grade 3 and 4 nonhematologic toxicity. Previous MESCC was associated with a greater risk of febrile neutropenia (OR, 2.74). The median progression-free survival (PFS) and overall survival (OS) were 6.4 and 15.4 months, respectively. Survival was similar in the older (age ≥ 75 years) and younger patients (PPFS= .66, POS= .90; log-rank) and when comparing patients undergoing dose reductions with patients treated with standard docetaxel throughout their treatment course (PPFS= .51 and POS= 0.52; log-rank). A longer interval from the primary diagnosis to the initiation of docetaxel (hazard ratio [HR], 1.00), baseline hemoglobin levels (HR, 0.85), Eastern Cooperative Oncology Group performance status > 0 to 1 (HR, 1.44), lactate dehydrogenase greater than the upper limit of normal (HR, 1.64), and prostate-specific antigen levels (HR, 1.00) were predictors of OS.



OS in the everyday clinical setting was inferior to that observed in randomized trials. Our results indicate that elderly patients and patients with moderate anemia or a history of MESCC at baseline have a greater risk of treatment-induced toxicity. Dose reductions did not compromise survival.
Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Electronic address: per.kongsted@regionh.dk.
Per
P
Kongsted
Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Inge Marie
IM
Svane
Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Henriette
H
Lindberg
Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Lisa
L
Sengeløv
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D018570:Risk Assessment; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D011239:Prednisolone; D007770:L-Lactate Dehydrogenase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
Docetaxel; Dose Reduction; Efficacy; Toxicity; mCRPC