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1.
Ann Oncol ; 23(8): 2072-2077, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22219016

RESUMO

BACKGROUND: Data are limited regarding bone metastases from colorectal cancer (CRC). The objective of this study was to survey the natural history of bone metastasis in CRC. PATIENTS AND METHODS: This retrospective, multicenter, observational study of 264 patients with CRC involving bone examined cancer treatments, bone metastases characteristics, skeletal-related event (SRE) type and frequency, zoledronic acid therapy, and disease outcomes. RESULTS: Most patients with bone metastases had pathologic T3/4 disease at CRC diagnosis. The spine was the most common site involved (65%), followed by hip/pelvis (34%), long bones (26%), and other sites (17%). Median time from CRC diagnosis to bone metastases was 11.00 months; median time to first SRE thereafter was 2.00 months. Radiation and pathologic fractures affected 45% and 10% of patients, respectively; 32% of patients had no reported SREs. Patients survived for a median of 7.00 months after bone metastases diagnosis; SREs did not significantly affect survival. Subgroup analyses revealed that zoledronic acid significantly prolonged median time to first SRE (2.00 months versus 1.00 month, respectively, P=0.009) and produced a trend toward improved overall survival versus no zoledronic acid. CONCLUSION: This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Colorretais/patologia , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Difosfonatos/uso terapêutico , Humanos , Imidazóis/uso terapêutico , Estudos Retrospectivos , Ácido Zoledrônico
2.
Clin Ter ; 162(3): 251-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21717054

RESUMO

Sunitinib malate (SU11248) is a multitarget oral tyrosine kinase receptor (RTKs) inhibitor which was approved by FDA in renal cells carcinoma (RCC) and imatinib-resistant or imatinib-intollerant gastro-intestinal stromal tumour (GIST). Sunitinib is able to inhibit RTKs such as receptors for platelet-derived growth factor (PDGF-Rα and ß) and for vascular endothelial growth factor (VEGFRs). It is able to inhibit KIT receptor, colony stimulating factor type 1 receptor (CSF-1R), glial cell line neutrophic factor receptor (RET), fms-like tyrosine kinase receptor-3 (FLT-3 or CD135), signal transducer and activator of transcription 3 (STAT3) and AKT (protein kinase B) in tumour cells. Many Sunitinib targets play important roles in growth and survival of human breast cancer (BC). The "rationale" of Sunitinib in BC (with or without others antiagiogenetic therapy) is its ability to block simultaneously intracellular portion of RTKs inhibiting many downstream signals. We overviewed the most relevant studies concerning Sunitinib in metastatic BC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Indóis/uso terapêutico , Pirróis/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Humanos , Sunitinibe
3.
Cancer Treat Rev ; 36 Suppl 3: S6-S10, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21129612

RESUMO

Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as "vicious circle," a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results from those in the advanced clinical phases are encouraging and underlined the need to design large randomised clinical trials to validate these results in the next future. Targeting the bone by preventing skeletal related events (SREs) and bone metastases has major clinical impact in improving survival in bone metastatic patients and in preventing disease relapse in adjuvant setting.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Neoplasias Ósseas/metabolismo , Catepsina K/efeitos dos fármacos , Catepsina K/metabolismo , Denosumab , Endotelinas/efeitos dos fármacos , Endotelinas/metabolismo , Humanos , Proteínas Proto-Oncogênicas pp60(c-src)/efeitos dos fármacos , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Ligante RANK/efeitos dos fármacos , Ligante RANK/metabolismo , Ligante RANK/uso terapêutico
4.
Clin Ter ; 161(5): 475-82, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20949248

RESUMO

Sunitinib malate (SU11248) is a multitarget oral tyrosine kinase receptor (RTKs) inhibitor which was approved by FDA in renal cells carcinoma (RCC) and imatinib-resistant or imatinib-intollerant gastrointestinal stromal tumour (GIST). Sunitinib is able to inhibit RTKs such as receptors for platelet-derived growth factor (PDGF-R alpha and beta) and for vascular endothelial growth factor (VEGFRs). It is able to inhibit KIT receptor, colony stimulating factor type 1 receptor (CSF- 1R), glial cell line neutrophic factor receptor (RET), fms-like tyrosine kinase receptor-3 (FLT-3 or CD135), signal transducer and activator of transcription 3 (STAT3) and AKT (protein kinase B) in tumour cells. Many sunitinib targets play important roles in growth and survival of human breast cancer (BC). The "rationale" of sunitinib in BC (with or without others antiagiogenetic therapy) is its ability to block simultaneously intracellular portion of RTKs inhibiting many downstream signals. We overviewed the most relevant studies concerning sunitinib in metastatic BC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Indóis/uso terapêutico , Pirróis/uso terapêutico , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Feminino , Humanos , Metástase Neoplásica , Sunitinibe
6.
Curr Cancer Drug Targets ; 9(7): 834-42, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20025571

RESUMO

This system constituted of the Receptor Activator of nuclear Factor-kB Ligand (RANKL), the Receptor Activator of Nuclear Factor-kB (RANK) and by the decoy Receptor Osteoprotegerin (OPG) plays a central role in bone resorption. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL.This review will critically describe and discuss the recent results of clinical trial investigating denosumab in different settings of medical oncology. In particular, we will report the recently published data of clinical trials investigating denosumab in prevention of cancer treatment induced bone loss (CTIBL), in prevention of skeletal related events (SREs) in bone metastatic patients and the ongoing studies in prevention of disease recurrence in the adjuvant setting of solid tumours. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of bone health care in cancer patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Ligante RANK/uso terapêutico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/farmacologia , Neoplasias Ósseas/fisiopatologia , Remodelação Óssea/fisiologia , Quimioterapia Adjuvante , Ensaios Clínicos como Assunto , Denosumab , Sistemas de Liberação de Medicamentos , Humanos , Modelos Biológicos , Ligante RANK/efeitos adversos , Ligante RANK/antagonistas & inibidores , Ligante RANK/farmacologia , Ligante RANK/fisiologia , Receptor Ativador de Fator Nuclear kappa-B/fisiologia
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