Expert review of anticancer therapy
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Expert Rev Anticancer Ther · Feb 2005
ReviewMolecular neuro-oncology and the development of targeted therapeutic strategies for brain tumors. Part 4: p53 signaling pathway.
Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches. Molecular neuro-oncology has now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targeted therapy. Loss of the tumor suppressor gene p53 and its encoded protein are the most common genetic events in human cancer and are a frequent occurrence in brain tumors. p53 functions as a transcription factor and is responsible for the transactivation and repression of key genes involved in cell growth, apoptosis and the cell cycle. ⋯ Molecular therapeutic strategies to normalize p53 signaling in cells with mutant p53 include pharmacologic rescue of mutant protein, gene therapy approaches, small-molecule agonists of downstream inhibitory genes, antisense approaches and oncolytic viruses. Other strategies include activation of normal p53 activity, inhibition of mdm2-mediated degradation of p53 and blockade of p53 nuclear export. Further development of targeted therapies designed to restore or enhance p53 function, and evaluation of these new agents in clinical trials, will be needed to improve survival and quality of life for patients with brain tumors.
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Alemtuzumab is a humanized monoclonal antibody against CD52, a small glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on normal T- and B-lymphocytes, and on a large proportion of malignant lymphoid cells, but not on hematopoietic progenitor cells. Over the past several years, a number of clinical trials have demonstrated the clinical activity of alemtuzumab in treating patients with chronic lymphocytic leukemia, T-cell malignancies such as T-prolymphocytic leukemia and cutaneous T-cell lymphoma, as well as in the prevention and therapy of graft-versus-host disease in the setting of allogeneic stem cell transplantation. ⋯ The most significant side effect of alemtuzumab is predisposition to infections related to the associated profound lymphopenia. Despite this, and with appropriate and more effective antibiotic prophylaxis, it is likely that we will witness an expansion of the role of alemtuzumab in the future.
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Expert Rev Anticancer Ther · Dec 2004
ReviewCapecitabine: the new generation of fluoropyrimidines in colorectal cancer.
Colorectal cancer is the second leading cause of cancer death in the USA and fluoropyrimidines have been the mainstay of treatment for over 40 years. Currently, capecitabine is the only orally available fluoropyrimidine approved for treatment in the USA. As a single agent it has demonstrated activity and equivalence to 5-fluorouracil (5-FU) intravenous administration via the Mayo Clinic regimen, in both the metastatic and adjuvant settings. Ongoing clinical trials are evaluating the efficacy of capecitabine in combination with oxaliplatin and irinotecan as more convenient substitutes for infusional 5-FU in the 5-FU/leucovorin/oxaliplatin and 5-FU/irinotecan regimens.
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Expert Rev Anticancer Ther · Oct 2004
Review Comparative StudyClinical management of medulloblastoma in adults.
Although medulloblastoma is the most common malignant brain tumor in children, 30% of cases occur in adults. Recent therapeutic advances in the treatment of average-risk childhood medulloblastoma have emphasized the reduction of treatment-related toxicity while improving progression-free survival. However, lessons learned from the pediatric experience have not been widely applied to the adult population in Phase II or randomized clinical trials. This review will compare adult and pediatric medulloblastoma, highlight case series of adults treated at major academic institutions, and suggest directions for the contemporary management of adults with medulloblastoma.
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Expert Rev Anticancer Ther · Oct 2004
ReviewAprepitant: a neurokinin-1 receptor antagonist for the treatment of chemotherapy-induced nausea and vomiting.
Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life, and although the use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, delayed nausea and vomiting remain a significant clinical problem. Aprepitant (Emend), Merck) is the first agent available in the new drug class of neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3 receptor antagonist and dexamethasone in patients receiving highly emetogenic chemotherapy, it improves the complete response rate of acute CINV. ⋯ Drug interactions should be monitored when aprepitant is coadministered with agents affected by CYP3A4 and CYP2C9 isoenzymes. The safety and efficacy of aprepitant has not been established in pediatric or adolescent patients, and aprepitant has not been evaluated in the treatment of patients with established nausea and vomiting. Future studies may consider the use of aprepitant with current and other new agents in moderately and highly emetogenic chemotherapy, as well in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.