Daniele Santini1, Saverio Cinieri2, Donatello Gasparro3, Roberto Bordonaro4, Pamela Francesca Guglielmini5, Vincenzo Emanuele Chiuri6, Rolando M D'Angelillo7, Giovanni Luca Ceresoli8, Daniele Fagnani9, Mirko Acquati10, Manlio Mencoboni11, Gaetano Lanzetta12, Donata Sartori13, Paolo Carlini14, Fabiana Panebianco15, Patrizia Beccaglia15, Giuseppe Procopio16. 1. Department of Oncology, Campus Bio-Medico University, Rome, Italy. 2. Medical Oncology Unit, Antonio Perrino Hospital, Brindisi, Italy. 3. Medical Oncology Unit, Department of General & Specialistic Medicine, University Hospital of Parma, Italy. 4. MD - ARNAS Garibaldi, Catania, Italy. 5. Medical Oncology Department, Ospedale SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy. 6. Medical Oncology Department, Ospedale Vito Fazzi, Lecce, Italy. 7. Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy. 8. Department of Oncology, Cliniche Humanitas Gavazzeni, Bergamo, Italy. 9. Medical Oncology Division - ASST, Vimercate, Italy. 10. Unit of Medical Oncology, Azienda Ospedaliera San Gerardo, Monza, Italy. 11. Oncology Unit, Villa Scassi Hospital, 16149 Genova, Italy. 12. Department Oncology and Palliative Care, INI Grottaferrata, Rome, Italy. 13. Oncology Unit, AULSS 3, Mirano, Italy. 14. Division of Medical Oncology 1, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy. 15. Medical Affairs Department, Oncology, Janssen-Cilag SpA, Cologno Monzese, Milan, Italy. 16. Department of Medical Oncology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, Italy.
Abstract
BACKGROUND: Bone remodeling is disrupted in metastatic disease, which affects > 70% of metastatic castration-resistant prostate cancer (mCRPC) patients. As a result, abnormal levels of specific bone turnover biomarkers (BTMs) are released. In this prospective ancillary analysis of the Italian real-world study ABITUDE, four markers were measured during abiraterone acetate plus prednisone (AAP) treatment in chemotherapy-naïve mCRPC men failing androgen-deprivation therapy. METHODS: Patients were enrolled if a blood sample was obtained before the first administration of abiraterone (baseline); ad-hoc blood samples were withdrawn during routine tests after 3, 6, and 12 months. A centralized lab measured bone alkaline phosphatase (BALP, osteoblast activity marker), type-I collagen-C-telopeptide (CTX-1, bone resorption marker), parathyroid hormone (PTH) and vitamin D (vitD). At each time point, intra-patient variations vs baseline were compared by the signed-rank test (statistical significance: P-value < 0.05). RESULTS: Of 481 patients enrolled in ABITUDE, 186 (median age: 76 [range: 53-93] years) met the substudy criteria: 74.7% had bone metastases, 11.8% were on bone-targeted therapies (BTT) and 14.0% on vitD supplementation. BALP decreased significantly at month 6 (P = 0.0010) and 12 (P < 0.0001) and CTX-1 at month 6 (P = 0.0028); PTH increased at month 3 (P < 0.0001); no significant difference in vitD levels was observed. Similar findings were observed in BTT-untreated patients. The reduction in BALP and CTX-1 levels was more pronounced in patients with than without bone metastases; in the latter group, no significant variation in BALP and CTX-1 levels was observed. CONCLUSIONS: AAP seems to exert an effect on the microenvironment of metastatic but not of normal bone, which likely contributes to its antitumoral activity.
BACKGROUND: Bone remodeling is disrupted in metastatic disease, which affects > 70% of metastatic castration-resistant prostate cancer (mCRPC) patients. As a result, abnormal levels of specific bone turnover biomarkers (BTMs) are released. In this prospective ancillary analysis of the Italian real-world study ABITUDE, four markers were measured during abiraterone acetate plus prednisone (AAP) treatment in chemotherapy-naïve mCRPC men failing androgen-deprivation therapy. METHODS: Patients were enrolled if a blood sample was obtained before the first administration of abiraterone (baseline); ad-hoc blood samples were withdrawn during routine tests after 3, 6, and 12 months. A centralized lab measured bone alkaline phosphatase (BALP, osteoblast activity marker), type-I collagen-C-telopeptide (CTX-1, bone resorption marker), parathyroid hormone (PTH) and vitamin D (vitD). At each time point, intra-patient variations vs baseline were compared by the signed-rank test (statistical significance: P-value < 0.05). RESULTS: Of 481 patients enrolled in ABITUDE, 186 (median age: 76 [range: 53-93] years) met the substudy criteria: 74.7% had bone metastases, 11.8% were on bone-targeted therapies (BTT) and 14.0% on vitD supplementation. BALP decreased significantly at month 6 (P = 0.0010) and 12 (P < 0.0001) and CTX-1 at month 6 (P = 0.0028); PTH increased at month 3 (P < 0.0001); no significant difference in vitD levels was observed. Similar findings were observed in BTT-untreated patients. The reduction in BALP and CTX-1 levels was more pronounced in patients with than without bone metastases; in the latter group, no significant variation in BALP and CTX-1 levels was observed. CONCLUSIONS: AAP seems to exert an effect on the microenvironment of metastatic but not of normal bone, which likely contributes to its antitumoral activity.
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