Core evidence
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Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and is universally fatal. Despite surgical resection, radiotherapy, and systemic chemotherapy, the median overall survival is less than 15 months. As current therapies are not tumor-specific, treatment commonly results in toxicity. ⋯ Side effects are minimal and mainly consist of hypersensitivity reactions. Due to the efficacy and safety of rindopepimut, it is a promising therapy for patients with GBM. Currently, rindopepimut is undergoing clinical testing in an international Phase III trial for newly diagnosed GBM and a Phase II trial for relapsed GBM.
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Soft tissue sarcoma accounts for less than 1% of all malignant neoplasms and is comprised of a very heterogeneous group of tumors with over 50 different subtypes. Due to its diversity and rarity, developing new therapeutics has been difficult, at best. The standard of care in the treatment of advanced and metastatic disease over the last 30 years has been doxorubicin and ifosfamide, either alone or in combination. There has been significant focus on developing new therapeutics to treat primary and metastatic disease. Trabectedin (ecteinascidin-743) is a tetrahydroiso-quinoline alkaloid which has been evaluated in the treatment of metastatic soft tissue sarcoma. ⋯ Trabectedin is a potential therapeutic option for the management of soft-tissue sarcoma. It appears to have specific activity in a select group of histologies, most notably myxoid/round cell liposarcoma. Although it would be helpful to study the use of trabectedin in a randomized, controlled fashion, the relative rarity of soft-tissue sarcoma, and heterogeneity of the histologic subtypes, makes phase III trials a difficult prospect.
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The selective neurokinin-1 receptor antagonist aprepitant is effective in the treatment of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with both moderately and highly emetogenic chemotherapy. Fosaprepitant has been developed as an intravenous prodrug of aprepitant. ⋯ Fosaprepitant and aprepitant are recommended in guidelines for preventing CINV due to moderately and highly emetogenic chemotherapy. Fosaprepitant is bioequivalent to aprepitant, and could offer potential benefits for patients who may be unable to tolerate oral administration of antiemetics during an episode of nausea or vomiting.
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Constipation is a distressing side effect of opioid treatment, being so irksome in some cases that patients would rather suffer the pain than the side effect of opioid analgesics. Stool softeners or stimulating laxatives are often ineffective or even aggravate the situation. A new efficacious and safe drug is needed to limit the frequently observed side effects induced by effective opioid-based analgesic therapy and to improve the quality of life for patients, most of whom are impaired by a severe disease. ⋯ Methylnaltrexone applied subcutaneously every other day may be given to patients suffering from chronic constipation due to opioid therapy for whom laxatives do not provide adequate relief of their symptoms.
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Sepsis and its sequelae are the leading causes of morbidity and mortality in critically ill patients. The burden to healthcare economies is also considerable. As the pathophysiology of sepsis is better defined, interventions aiming to treat sepsis are emerging. Eritoran (E5564), a toll-like receptor 4 (TLR4)-directed endotoxin antagonist, is one such emerging therapeutic option for treatment of sepsis. ⋯ Eritoran is a potential therapeutic option for management of sepsis and other TLR4- and lipopolysaccharide-mediated disorders with a reasonable safety and tolerability profile that must be validated by several rigorous, blinded, placebo-controlled, adequately powered, multicenter, randomized clinical trials.