Oncology
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Breast tumorigenesis is a continuum from preinvasive lesions to early breast cancer and advanced disease. In this article the data supporting the use of the aromatase inhibitor anastrozole in postmenopausal women across this continuum are reviewed. In advanced disease, anastrozole has a significant survival benefit and tolerability advantage compared with megestrol acetate when used as second-line treatment. ⋯ Finally, anastrozole substantially reduces the incidence of contralateral breast cancer compared with tamoxifen in women with HR+ early breast cancer and, therefore, is a potential chemopreventive agent. Anastrozole is thus positioned to become the standard care for postmenopausal women with HR+ disease across the whole breast cancer continuum. Additional data from ongoing studies will further clarify the role of anastrozole across the continuum and answer outstanding questions regarding the optimal timing and duration of treatment.
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Because of its proven efficacy profile based on long-term data, tamoxifen has been the standard adjuvant endocrine therapy for hormone-sensitive early breast cancer for the past 30 years. However, there is well-established evidence that long-term use of tamoxifen is associated with serious side effects. As adjuvant endocrine therapy is generally administered for long periods of time, the safety and tolerability of agents used in this setting are of particular importance. ⋯ The AIs have differing pharmacological profiles, which may translate into dissimilar adverse event profiles in the adjuvant treatment setting, but patient follow-up in most trials is relatively short to make a valid comparison. It cannot, therefore, be assumed that all AIs will be equally well tolerated in the adjuvant setting. Further data on the long-term safety of AIs other than anastrozole are therefore required to allow overall risk:benefit assessments on these agents to be made.
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Newer-generation intravenous bisphosphonates have resulted in the reduction of skeletal-related complications, i.e. skeletal-related events (SREs) such as pain, hypercalcemia, pathologic fractures and spinal cord and nerve compression, as well as improvements in the quality of life in patients with metastatic bone disease who are likely to have a prolonged clinical course. Highly potent, nitrogen-containing bisphosphonates such as zoledronic acid reduce SREs in patients with bone metastases from other solid tumors (including lung cancer). Part one of our review discussed the mechanisms of action by bisphosphonates as well as potential roles for bone markers and imaging in lung cancer. In this article, part two of our review, we examine the economic and clinical impact of bisphosphonates in lung cancer, with a focus on the potential role of newer-generation bisphosphonates in the management of advanced, metastatic bone disease of lung cancer.
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New drugs improved efficacy or convenience of treatment in metastatic colorectal cancer. The oral fluoropyrimidines capecitabine and UFT are less toxic but equally efficacious relative to intravenous bolus 5-fluorouracil (5-FU)/folinic acid (FA). These agents might be beneficial for patients who unlikely benefit from the more intensive combination therapy with infusional 5-FU/FA and irinotecan or oxaliplatin. ⋯ New targets in the treatment of colorectal cancer are the EGF and VEGF receptor. The monoclonal EGF receptor antibody cetuximab alone and in combination with irinotecan is active in second-line treatment. The VEGF antibody bevacizumab prolongs survival when given in combination with 5-FU/FA and irinotecan.
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Ifosfamide is relatively well tolerated but it can be associated occasionally with life-threatening complications such as arrhythmias and heart failure, severe encephalopathy and hemorrhagic cystitis. Mesna administration can control the urothelial toxicity of ifosfamide, but it is without effect on the other complications. Other preventive measures, such as amifostine or methylene blue administration, have not yet been adequately evaluated in a sufficient number of patients. Clinicians prescribing ifosfamide, especially in high doses, should be watchful for early signs of toxicity in order to discontinue ifosfamide administration soon enough to avoid development of major toxicity.