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The use of azanucleosides has altered the treatment paradigm of myelodysplastic syndromes. Recently, treatment with 5-azacitidine was demonstrated to prolong survival in patients with myelodysplastic syndromes for the first time. This Review discusses the potential of these forms of treatment as monotherapy and in combination, and assesses the most recent clinical data.
EGFR is one of the most studied targets in oncology, and several inhibitors have shown promising results in selected patient populations. However, intrinsic and acquired resistance to these targeted therapies is increasingly recognized. The authors of this Review describe the successful translation of EGFR inhibitors to the clinic, and highlight the mechanisms of resistance to these agents that limit their long-term efficacy. Understanding these processes will allow researchers to develop therapies that overcome resistance and ultimately lead to more successful outcomes.
Survival outcomes for advanced or metastatic non-small-cell lung cancer remain poor; however, molecular targeted agents offer new opportunities provided that patients are selected for treatment according to their tumor profile. This Review highlights the promising activity shown with novel targeted therapies that interfere with the IGF-1R pathway and agents that inhibit the EML4-ALK fusion protein. Aberrations in other key signaling pathways that have been identified as crucial targets, especially in resistant patients, are also discussed.
Metronomic chemotherapy is the chronic administration of chemotherapeutic agents at relatively low, minimally toxic doses, and with no prolonged drug-free breaks. This type of chemotherapy inhibits tumor growth primarily through anti-angiogenic mechanisms. The latest clinical trials of metronomic chemotherapy in adult and pediatric cancer patients are discussed and the authors highlight the research efforts that need to be made to facilitate the optimal development of metronomic chemotherapy in the clinic.
A recent landmark study reported the long-term results that compared a standard course of whole-breast irradiation (25 treatments over 5 weeks) with a hypofractionated course of radiation (16 treatments over 3.5 weeks) in patients with early-stage, node-negative breast cancer. The trial demonstrated equivalence of results with respect to overall survival, local control, toxicity and cosmetic outcomes.
Prognostic models for patients with Hodgkin lymphoma are imperfect and do not allow a precise individualized therapy. A recent gene-expression profiling study, translated into a routine immunohistological test, identified genes of tumor-associated macrophages as being responsible for treatment outcome in patients with Hodgkin lymphoma. If this finding is confirmed by other investigators, it could be a major step towards personalized therapy for patients with Hodgkin lymphoma.
Management of high-risk non-muscle-invasive bladder cancer represents a difficult challenge in clinical practice. The dilemma is to decide between an organ-sparing approach or radical cystectomy with the risk of undertreatment or overtreatment for this group of patients. This issue is especially important for patients who have failed previous intravesical therapy.
Although high-dose methotrexate is widely accepted as the most effective chemotherapeutic agent for primary CNS lymphoma, no optimal dose or dosing strategy has been established. Researchers from the International Extranodal Lymphoma Study Group used clinical trial data to explore whether or not an area under the curve model might be useful to optimize methotrexate dosing. The results strongly suggest that effective methotrexate dose is an important variable in patient outcome.
