Expert review of anticancer therapy
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Expert Rev Anticancer Ther · Jun 2003
ReviewTargeting epidermal growth factor receptor: novel therapeutics in the management of cancer.
Overexpression of epidermal growth factor receptor (EGFR) in epithelial tumors, including head and neck, lung, breast, colon and other solid tumors, has frequently been correlated with poor prognosis, thus stimulating efforts to develop new cancer therapies that target EGFR. Monoclonal antibodies and tyrosine kinase inhibitors specifically targeting EGFR are the most well-studied and hold substantial promise of success. Several compounds of monoclonal antibodies and tyrosine kinase inhibitors targeting EGFR have been studied and clinical trials are now underway to test the safety and efficacy of these targeting strategies in several human tumors. ⋯ EGFR targeted treatment by monoclonal antibodies and tyrosine kinase inhibitors have been proven to sensitize tumor cells to the effects of chemotherapy and radiation therapy. The synergistic activities and nonoverlapping toxicities of these compounds allow concomitant administration with cytotoxic therapy. Challenges of evaluating EGFR targeted agents exist in selecting the optimal dosages and determining long-term toxicity.
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Expert Rev Anticancer Ther · Apr 2003
ReviewAromatase inhibitors for treatment of postmenopausal patients with breast cancer.
The third generation of aromatase inhibitors and inactivators, such as anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin), have become available for treatment of postmenopausal breast cancer patients. Several clinical trials have demonstrated that these new drugs can achieve better treatment results than megestrol acetate (Megace) and may replace tamoxifen for the first-line hormonal therapy for metastatic breast cancer patients. In fact, these drugs are now used in many hospitals and clinics for patients with metastatic breast cancer who were previously given tamoxifen as adjuvant treatment. ⋯ Additional data regarding survival resulting from comparative trials of letrozole and tamoxifen and of exemestane and tamoxifen are expected to be available in a few years. However, limited information is available regarding adverse events caused by long-term administration of aromatase inhibitors. Longer follow-up is needed to determine the efficacy and safety of these new aromatase inhibitors when used for adjuvant treatment of postmenopausal patients with breast cancer.
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The recent clinical and commercial success of anticancer antibodies, such as rituximab (Rituxan) and trastuzumab (Herceptin) has created great interest in antibody-based therapeutics for hematopoietic malignancies and solid tumors. Given the likely lower toxicity for antibodies versus small molecules, the potential increase in efficacy by conjugation to radioisotopes and other cellular toxins and the ability to characterize the target with clinical laboratory diagnostics to improve the drug's clinical performance, it is anticipated that current and future antibody therapeutics will find substantial roles alone and in combination therapy strategies for the treatment of patients with cancer. ⋯ However, although there are a large number of agents in both early and later stages of clinical development, only a handful will make it through regulatory approval and become successful products. This review considers the structure of anticancer therapeutic antibodies, the techniques used to reduce their antigenicity, factors that influence efficacy and toxicity, conjugation with isotopes and toxins and antibody target validation.
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Cancer-related fatigue is now a recognized phenomenon with an established diagnosis. Fatigue is the most common symptom experienced by cancer patients and in many cases, the challenge of alleviating its severity is daunting for the clinician. ⋯ Research of cancer-related fatigue treatment is in its infancy and future clinical trials examining the effects of various pharmacologic and nonpharmacologic therapies for cancer-related fatigue are needed. The development of effective therapies for the treatment of cancer-related fatigue could profoundly affect the lives of many cancer patients.
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The statistics on lung cancer survival remain disappointing and form a powerful argument to develop new methods to control this most deadly form of cancer in both men and women. Chemoprevention is one of these new approaches. While carcinogens from cigarette smoke form an essential link between nicotine addiction and lung cancer, several investigations confirm that dietary and genetically determined factors play an important role in modulating the individual susceptibility and are linked to the chemoprevention approach. ⋯ On the other hand, recent progress in molecular biology has led to the discovery of specific approaches to chemoprevention and there considerable optimism regarding the potential of molecules and antibodies that target specific receptors or mutations. Epidermal growth factor receptor blocking agents, farnesyltransferase and cyclooxygenase inhibitors and 9-cis retinoic acid have been identified as promising candidates for studies in high risk populations. After more than 20 years of worldwide research, the prospects for effective lung cancer treatment are better than ever.