RESUMO
BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.
RESUMO
INTRODUCTION: Treatment of HER-2-negative metastatic breast cancer (MBC) patients after anthracycline exposure is controversial. Docetaxel/capecitabine is a promising regimen, but the administration schedule is not well established. MATERIALS AND METHODS: Treatment included 3 cycles of docetaxel 100 mg/m2 day 1 every 21 days followed by 3 cycles of capecitabine 1250 mg/m2/12 h days 1-14. Patients not progressing were maintained with capecitabine 900 mg/m2/12 h on days 1-14 every 21 days until progression or unacceptable toxicity. RESULTS: Fifty-three anthracycline-pretreated patients were enrolled: median age 54 years, ECOG grade 0-1 86.7%. Most of the women received adjuvant chemotherapy (81%) and 5 patients (9%) had had prior metastatic chemotherapy treatment. Median time from anthracycline exposure was 29 months. ORR (intent-to-treatment analysis) after the sequential therapy was 51% (CI 95% 37-65) with 15% (CI 95% 7-28) of patients reaching complete responses. Median time to progression was 8.2 (CI 95% 7.1-10.7) months, with 61.9% (CI 95% 45.6-76.4) of the patients free of disease after 6 months. Median overall survival was not reached after a median follow-up of 10.4 months, and 75% of the patients were alive after 14.3 months. Survival rate after 12 months was 81.1% (CI 95% 68.0-90.6). The most frequent NCI grade 3-4 toxicities were hair loss (28.3%), asthenia (15.1%), stomatitis (11.32%) and nausea (11.32%). Severe hand-foot syndrome rate was 7.5%. CONCLUSIONS: Sequential docetaxel-capecitabine is feasible, effective and well tolerated in first-line MBC treatment. Evaluation of this schedule in randomised studies is warranted.