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Gastrointestinal stromal tumors (GIST) are neoplasms of mesenchymal origin arising from the GI tract. These tumors are characterized by activating mutations of the receptor tyrosine kinases, either KIT or PDGFRa, which are found in 85% of cases. Despite the use of imatinib in first-line and sunitinib in second-line treatment, patients with metastatic GIST still have a high risk of progression and death. To date, the median overall survival for metastatic disease is close to 5 years. Treatment with imatinib, an inhibitor of KIT and PDGFRa, results in clinical benefit, that is, objective responses or disease stabilization in approximately 85% of patients with unresectable or metastatic GISTs. However, metastatic GIST develop resistance to imatinib at a median time of 24 months, and sometimes more than 8 years after initiation of the treatment. In addition, as many as 15% of patients do not respond initially to imatinib; therefore, novel therapeutic options, new drugs or combination are needed. Genotypic ana...

Patients with low-risk neutropenic fever as defined by the Multinational Association of Supportive Care in Cancer (MASCC) score might benefit from ambulatory treatment. Optimal management remains to be clearly defined, and new oral antibiotics need to be evaluated in this setting.Cancer patients with febrile neutropenia and a favorable MASCC score were randomized between oral moxifloxacin and intravenous ceftriaxone. All were fit for early hospital discharge. The global success rate was related to the efficacy of monotherapy, as well as to the success of ambulatory monitoring.The trial was closed prematurely because of low accrual. Ninety-six patients were included (47 in the ceftriaxone arm and 49 in the moxifloxacin arm). A total of 65% were women, 30.2% had lymphoma, 34.4% had metastatic, and 35.4% had non-metastatic solid tumors. The success rates of home antibiotics were 73.9% and 79.2% for ceftriaxone and moxifloxacin, respectively. Seven patients were not discharged, and 14 required re-hospitalization. There were 17% of microbiologically documented infections that were, in most cases, susceptible to oral monotherapy.These results suggest that MASCC is a valid and useful tool to select patients for ambulatory treatments and that oral moxifloxacin monotherapy is safe and effective for the outpatient treatment of cancer patients with low-risk neutropenic fever.

International audience; INTRODUCTION: Soft-tissue sarcomas (STS) represent a heterogeneous group of malignant tumors originating from connective tissues. Over recent years, this heterogeneity has led to a molecular breakdown of STS and subsequent use of targeted agents in several molecularly defined subgroups. After the initial success of imatinib in gastrointestinal stromal tumors, several other compounds have shown promising activity in some but not all subgroups of sarcoma. AREAS COVERED: This review discusses the rational and clinical results, when available, that support this subtype-directed approach. In the vast majority of cases, these agents have been tested only in patients with advanced disease; as chemotherapeutic agents are developed as non-histotype-specific therapies, they are not discussed here. The PubMed literature was searched using the terms 'sarcoma', 'angiogenesis', 'mTOR' and 'targeted agents'. Proceedings of the annual meeting of the American Society of Clinical Oncology as well as those of the Connective Tissue Oncology Society were also searched for relevant information. EXPERT OPINION: Many agents are currently developed in a subtype-specific manner in STS and this represents a significant leap forward. However, much remains to be done to improve our understanding of the molecular biology of this heterogeneous group of diseases.