Seminars in oncology
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Seminars in oncology · Jun 2006
ReviewCardiotoxic consequences of anthracycline-containing therapy in patients with breast cancer.
In women, breast cancer is the second most common form of cancer and the leading cause of death caused by malignancy. The anthracycline antibiotics are potent anti-tumor agents used in a wide spectrum of malignancies. They are part of the gold standard adjuvant therapy for breast cancer and in metastatic disease they provide significant increases in response rate, time to disease progression, and overall survival. ⋯ The onset of clinical and subclinical cardiac damage is delayed and occurs more than 3 months after the cessation of treatment, indicating a crucial time for functional impairment to occur and highlighting the ineffectiveness of monitoring left ventricular ejection fraction as an endpoint during anthracycline therapy. Possible future treatment options for managing anthracycline-induced cardiotoxicity include agents such as dexrazoxane that prevent oxygen-free radical generation. Further investigation is required into the use of angiotensin-converting enzyme inhibitors to redress cardiac damage and new methods of identifying patients at high risk of congestive heart failure before cardiac damage has occurred.
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Seminars in oncology · Apr 2006
ReviewManagement of cancer-treatment-induced bone loss in postmenopausal women undergoing adjuvant breast cancer therapy: a Z-FAST update.
The prevention of cancer-treatment-induced bone loss (CTIBL) in long-term adjuvant breast cancer therapy is a high priority. Postmenopausal women with cancer, already at increased risk of bone loss because of age-related estrogen deficiency, face accelerated bone loss with the use of estrogen-depleting therapies such as third-generation aromatase inhibitors (AIs). Although effective in reducing cancer recurrence rates in the adjuvant setting, AIs are associated with bone loss and an increased risk of fractures. ⋯ At 6 months, assessable women in the upfront group showed a mean increase of 1.55% in lumbar spine (L1 - L4) BMD, compared with a mean decrease of 1.78% in women in the delayed group, resulting in a difference of 3.33% between groups; moreover, women in the former group showed a mean increase of 1.02% in total hip BMD, compared with a mean decrease of 1.40% in those in the latter group, resulting in a significant difference of 2.42% between groups (P <.001). Thus, the Z-FAST BMD results show that upfront zoledronic acid prevents CTIBL in postmenopausal women receiving adjuvant letrozole therapy for early breast cancer. Combining the anticancer efficacy of letrozole with the bone-protective effect of zoledronic acid may be a successful treatment in this setting.
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The majority of patients with ovarian cancer will relapse despite state-of-the-art first-line surgery and chemotherapy. There are two subgroups of patients with recurrent ovarian cancer: those with platinum-resistant disease and those with platinum-sensitive disease. Re-treatment with single-agent platinum has long been considered standard therapy for patients with platinum-sensitive disease, and, based on its favorable therapeutic profile, carboplatin has become the treatment agent of choice. ⋯ The toxicity profiles and schedules of carboplatin plus paclitaxel and carboplatin plus gemcitabine are different, with the taxane combination having greater neurotoxicity and alopecia, less hematologic toxicity, and requiring longer drug infusions (although fewer days of treatment per cycle) than the gemcitabine combination. Based on the results of these two trials, combination chemotherapy should be considered the standard treatment of recurrent platinum-sensitive ovarian cancer. The choice of treatment needs to take into account the increase in side effects when using combination chemotherapy compared with carboplatin monotherapy, and the different toxicities of the two combination regimens.
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Seminars in oncology · Apr 2006
ReviewThe role of alemtuzumab in nonmyeloablative hematopoietic transplantation.
Nonmyeloablative stem cell transplants provide a viable therapeutic option for older patients or patients with comorbid conditions, who were previously deemed to be ineligible for transplantation. Despite improvements in clinical outcomes, graft-versus-host disease (GVHD) remains a significant and potentially lethal complication. One approach by which GVHD has been managed is through introduction of new agents, such as alemtuzumab, into the conditioning regimen. ⋯ Furthermore, in chronic lymphocytic leukemia therapy, alemtuzumab has been shown to purge malignant cells from the host to allow for harvesting for the purpose of autologous transplantation. Despite results showing that alemtuzumab can play an important role in managing GVHD, little information is available regarding a standardized dosing schedule. Greater insight into alemtuzumab's pharmacokinetic activity would assist in developing a schedule that can optimize alemtuzumab-mediated T-cell depletion to prevent GVHD, while retaining sufficient host T-cell activity to encourage the graft-versus-leukemia effect and prevent relapse.
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Seminars in oncology · Feb 2006
ReviewOptimizing therapy in previously treated non-small cell lung cancer.
The past decade has seen the identification of several novel cytotoxic agents. More recently, targeted therapies with single-agent activity or that enhance the efficacy of chemotherapy in advanced non-small cell lung cancer have been identified. ⋯ The cytotoxic agents docetaxel, pemetrexed, and topotecan, as well as the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib, have been evaluated in phase III trials in previously treated populations. This review summarizes the results of these phase III studies with a particular focus on predictors of favorable outcome, attempts to provide a rational approach to therapeutic selection in this patient population, and discusses ongoing pivotal trials and future strategies in this field.