RESUMO
Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin, and a paradigmatic model for a successful rational development of targeted therapies in cancer. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. These guidelines are elaborated by the conjoint effort of the Spanish Society of Medical Oncology (SEOM) and the Spanish Sarcoma Research Group (GEIS) and provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.
Assuntos
Tumores do Estroma Gastrointestinal , Sarcoma , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/terapia , Oncologia , Consenso , Receptores Proteína Tirosina QuinasesRESUMO
Soft tissue sarcomas are uncommon tumors of mesenchimal cell origin. Criteria for suspicion is a soft tissue mass that is increasing in size, and has a size greater than 5 cm or is located under the deep fascia. Diagnosis and management of these patients should preferably be performed by a specialist multidisciplinary team in a referral center. Assessment of a patient with a suspect of sarcoma should include magnetic resonance and biopsy performed prior to surgery. Primary local therapy for patients with localized sarcoma is based on wide surgical resection with a tumor-free tissue margin, in association in most cases with radiotherapy. Adjuvant chemotherapy constitutes an option that could be considered in high-risk sarcomas of the extremities. When metastasis are present, surgery of pulmonary lesions, in some selected patients, and chemotherapy are current available options.
Assuntos
Guias de Prática Clínica como Assunto , Sarcoma/terapia , Adulto , Algoritmos , Árvores de Decisões , Humanos , Oncologia/legislação & jurisprudência , Metástase Neoplásica , Estadiamento de Neoplasias/métodos , Sarcoma/diagnóstico , Sarcoma/patologia , EspanhaRESUMO
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs are characterised by the expression of KIT, a type III tyrosine kinase receptor, and the presence of mutations in KIT or PDGFRA in about 80-85% of cases. The primary treatment for GIST is surgery, which cures most patients with low- or intermediate-risk tumours. The introduction of the kinase inhibitor imatinib mesylate, and sunitinib in second line, against KIT and PDGFRA has provided the first evidence of directed therapy in GIST. The aim of this review is to highlight the growing evidence that KIT and PDGFRA genotyping provides valuable information for the clinical management of GIST patients. We show that KIT and PDGFRA genotyping has emerged as one of the principal factors in the evaluation of GISTs, particularly in those tumours that are clearly malignant or have a high risk of recurrence. In addition to helping establish the diagnosis of GIST in unusual cases, genotyping can be very useful to physicians and patients in deciding on imatinib dose, in estimating the likelihood and duration of benefit, and potentially in selecting second-line therapies.
Assuntos
Tumores do Estroma Gastrointestinal/genética , Proteínas Proto-Oncogênicas c-kit/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Antineoplásicos/uso terapêutico , Benzamidas , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Genótipo , Humanos , Mesilato de Imatinib , Mutação , Piperazinas/uso terapêutico , Pirimidinas/uso terapêuticoRESUMO
INTRODUCTION: This phase II study was designed to evaluate the efficacy of vinorelbine in combination with estramustine in patients with chemotherapy-naïve hormone-refractory prostate cancer. MATERIAL AND METHODS: Patients received vinorelbine (i.v. 25 mg/m2) on days 1 and 8 every 3 weeks and estramustine (oral, 600 mg/m2) daily. Eligible patients were required to have progressive metastatic disease following the first hormonal manipulation. RESULTS: Of the 51 patients enrolled (median age = 69 years), 84% presented bone involvement and 75% had at least two organs involved at the time of study entry and 47 were evaluable for treatment efficacy. Prostate specific antigen (PSA) response (> or =50% decrease) which was the primary efficacy criterion was reported in 21 patients (41.2%) in the intent-to-treat (ITT) population and in 20 patients (48.8%) in the per protocol (PP) population. Of the 7 patients with measurable disease, 2 achieved partial response. Median progression-free survival and overall survival were 4.7 months (range: 1.9-8.6) and 14.3 months (range: 4.2-21.2), respectively. Grade 3-4 neutropenia was reported in 6.1% of patients and in 1% of cycles. The incidence of complicated neutropenia (febrile neutropenia reported in 1 patient and septic shock with severe neutropenia reported in 2 patients) was 5.8%. The most frequent grade 3-4 non-haematological events (% of patients > or =5%) included anorexia (10%), thrombosis/embolism (8%), vomiting and hypotension (6% each). There were 3 toxic deaths (5.9 %) resulting from pulmonary embolism, angina pectoris, and septic shock. The impact of combined chemotherapy on the quality-of-life (QL) of the patients was assessed between baseline and the first evaluation scheduled at 6 weeks indicated a marked reduction in pain while the rest of the symptoms remained stable. Overall, health status improved slightly over the treatment period. CONCLUSIONS: This study confirmed that the combination of vinorelbine and estramustine is an active regimen in patients with hormone-resistant prostate cancer who had not been treated previously with chemotherapy. Main toxicities included complicated neutropenia even though the incidence of severe neutropenia was low. We observed a higher incidence of toxic deaths which could have been related to the regimen of estramustine used in the study.