docMetastasi Ossee - Congressi AIRO
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Metastasi Ossee - Congressi AIRO
Taranto – 16 Marzo 2007 Metasta si Ossee Nicolangelo Calvi Metasta si Ossee Metasta si Ossee 10 Metasta si Ossee Metasta si Ossee TTum umoorr cceells llsggro rowth wth Tum o r c e ll Tum o r c e lls c he m o ta xis PTHrP PTHrP PTHrP Bo Bone ne ddeerived rived ggro rowth wth fa faccto tors rs Metasta si Ossee Primary Tumor Site Breast Prostate Thyroid Kidney Bronchus Esophagus Gastrointestinal Rectum No. Of Studies 5 6 4 3 4 3 4 3 Incidence % of Bone Metastases Median Range 73 68 42 35 36 6 5 11 47-85 33-85 28-60 33-40 30-55 5-7 3-11 8-13 Metasta si Ossee 4 C Y T O T O X IC D R U G S a s first trea tm en t in b on e m eta stas es Not hormonoresponsive tumors Lymphangitic pulmonary metastases Liver metastases compromised hepatic function Need of a rapid response Metasta si Ossee Metasta si Ossee Metasta si Ossee R ed u ctio n o f b o n e m eta sta ses rela ted p a in as a n ew m a rk er o f tu m o r resp o n se Metasta si Ossee Metasta si Ossee Primary Tumor Site Breast Prostate Thyroid Kidney Bronchus Esophagus Gastrointestinal Rectum No. Of Studies 5 6 4 3 4 3 4 3 Incidence % of Bone Metastases Median Range 73 68 42 35 36 6 5 11 47-85 33-85 28-60 33-40 30-55 5-7 3-11 8-13 Cumulative survival Metasta si Ossee Bone metastases Visceral metastases Time Metasta si Ossee Metasta si Ossee Metasta si Ossee Metasta si Ossee Metasta si Ossee C yto to xic c h e m o the ra p y fo r ADVANC ED h o rm o ne -re sista n t PRO STATE C ANC ER Ya goda A, PetrylaK D hormone-refractory prostate cancer unresponsive to cytotoxic agents. documentation of response complicated by a lack of established criteria to judge activity in a disease in which few patients had measurable soft tissue lesions Cancer, 1993 Feb 1; 71(3 Suppl.): 1098-109 Metasta si Ossee SWO G 9 91 6 a nd TAX32 7 Co m pa riso n o f B a selin e Cara cteristics of Pa tients R an do m ly a ssigned to th e Tra ils Metasta si Ossee Metasta si Ossee TAX3 2 7 tria l Metasta si Ossee E ffica cy o utco m es fro m th e TA X 3 2 7 tria l Metasta si Ossee Kaplan-Meier Estimates of the Probability of Overall Survival in the Three Groups Tannock I et al. N Engl J Med 2004;351:1502-1512 Metasta si Ossee F u tu re fo r th e Trea tm ent o f P ro sta te C a ncer w ith B O N E M E TA S TA S E S Classic cytotoxic agents Vaccines Radiolabeled moAb Targeted agents Metasta si Ossee Satraplatin SPARC tria l Satraplatin + prednisone pts Placebo + prednisone Metasta si Ossee A tra senta n Endothelin-A receptor (ETAR) antagonist Endothelin-1 (ET-1) is implicated in the development of the osteoblastic bone lesions that characterize metastatic disease. SWOG S0421 trial, a randomized, placebo-controlled phase III trial designed to compare docetaxel, prednisone, and atrasentan with docetaxel plus prednisone alone in men with advanced HRPC. Metasta si Ossee Ca lcitriol Antiproliferative and proapoptotic effects in prostate cancer ASCENT trial randomized, double-blinded, placebo-controlled trial evaluating the combination of docetaxel with the proprietary high-dose calcitriol formulation DN-101 Metasta si Ossee Th alidom ide B evacizu m a b Thalidomide is a putative angiogenesis inhibitor. It inhibits angiogenesis and reduces VEGF levels Bevacizumab, a humanized monoclonal antibody that targets VEGF The National Cancer Institute is currently conducting a phase II study of a four-drug combination consisting of docetaxel, prednisone, thalidomide, and bevacizumab in men with chemotherapy-naive progressive HRPC, and the CALGB is coordinating a phase III, double-blinded, placebo-controlled trial of docetaxel plus prednisone with or without bevacizumab Metasta si Ossee Gleevec Inhibitor of PDGF-receptor signalling pathway implicated in tumor angiogenesis and bone formation. Administered with zolendronic acid and paclitaxel in an experimental model of bone metastases of human prostate cancer Combination with docetaxel Metasta si Ossee PSA, prostatic acid phosphatase, and prostate membrane antigens have been used as targets for developing immunotherapy. Metasta si Ossee Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S SANTINI ET AL. NATURE CLINICAL PRACTICE ONCOLOGY JUNE 2006 VOL 3 NO 6 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S SANTINI ET AL. NATURE CLINICAL PRACTICE ONCOLOGY JUNE 2006 VOL 3 NO 6 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S SANTINI ET AL. NATURE CLINICAL PRACTICE ONCOLOGY JUNE 2006 VOL 3 NO 6 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S SANTINI ET AL. NATURE CLINICAL PRACTICE ONCOLOGY JUNE 2006 VOL 3 NO 6 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S SANTINI ET AL. NATURE CLINICAL PRACTICE ONCOLOGY JUNE 2006 VOL 3 NO 6 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S Pa c lita xe l th e n Zo le n d ro n ic a c id Neville-Webbe HL et al. (2006)Tumor Biol 27:92–103 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S Pa c lita xe l a n d Zo le n d ro n ic a c id Neville-Webbe HL et al. (2006)Tumor Biol 27:92–103 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S Neville-Webbe HL et al. (2006)Tumor Biol 27:92–103 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S SANTINI ET AL. NATURE CLINICAL PRACTICE ONCOLOGY JUNE 2006 VOL 3 NO 6 Metasta si Ossee S y n erg istic a ctio n o f C Y T O T O X IC D R U G S a n d B I SP H O S P H O N AT E S conclusions In the clinic, chemotherapy and bisphosphonates are not given in any particular sequence, and tratment intervals vary; preclinical data indicate that to achieve maximum effects from the combination of treatments, the sequence and the timing of drug administration have an important role and could determine the efficacy of the therapy, both in advanced disease and in the adjuvant setting.
