Per Kongsted1, Inge Marie Svane2, Henriette Lindberg2, Lisa Sengeløv2. 1. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Electronic address: per.kongsted@regionh.dk. 2. Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Abstract
BACKGROUND: 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. PATIENTS AND METHODS: Medical records from 421 consecutive patients treated with first-line docetaxel (75 mg/m2 every 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. PATIENTS AND METHODS: Medical records from 421 consecutive patients treated with first-line docetaxel (75 mg/m2 every 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. RESULTS: 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. CONCLUSIONS: 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.
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