Clinical advances in hematology & oncology : H&O
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Pulmonary hypertension (PH), a disorder characterized by elevated pulmonary artery pressure and pulmonary vascular resistance, is an increasingly recognized complication of sickle cell disease (SCD), with a prevalence of approximately 30% in adult patients. It confers a high risk of death, with 2-year mortality rates of 40-50%, even at modest elevations of pulmonary pressures. The pathogenesis of PH complicating SCD is probably heterogeneous, including hemolysis and its effect on nitric oxide bioavailability, asplenia, thrombosis, chronic lung disease, and iron overload. ⋯ Current data on treatment of PH in SCD are limited. Recommendations include intensification of sickle cell-directed therapies, treatment of causal factors or associated diseases, general supportive measures, and use of PH-specific pharmacologic agents. Further knowledge of the pathobiology of this complication and clinical trials of effective therapy are needed to improve survival.
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The development of new anti-myeloma agents with different mechanisms of action from conventional chemotherapy has necessitated a new look at clinical trial design. We discuss design issues for cytostatic agents for phase I, II, and III clinical trials pertaining to myeloma. The success of phase I trials with cytotoxic agents is predicated on the dose toxicity curve being strictly monotone. ⋯ The appropriateness of different endpoints in phase II myeloma trials is discussed. The goal of phase III clinical trials for cytostatic agents is typically twofold: to determine efficacy of the new agent for all patients and for the subset of patients with a certain biomarker. We present different trial designs that can address both aims.
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Antiangiogenic therapy has emerged as an important concept in the treatment of solid tumors, including non-small cell lung cancer (NSCLC). Vascular endothelial growth factor (VEGF) represents an important therapeutic target, as it is the primary mediator of angiogenesis and is induced by multiple tumor-relevant stimuli. The anti-VEGF monoclonal antibody bevacizumab has demonstrated a significant clinical benefit in patients with non-squamous cell NSCLC in a randomized phase III trial. ⋯ In some cases, combination therapy with different targeted agents may provide the most comprehensive treatment approach. In a randomized phase II study, bevacizumab in combination with the epidermal growth factor receptor inhibitor erlotinib demonstrated efficacy similar to chemotherapy plus bevacizumab. Ongoing studies are continuing to investigate new agents and identify the patients most likely to benefit from antiangiogenic therapy.