Seminars in oncology
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Seminars in oncology · Apr 2006
Randomized Controlled Trial Multicenter StudyPreventing relapse beyond 5 years: the MA.17 extended adjuvant trial.
For patients with hormone-receptor-positive breast cancer, the risk of relapse remains significant even after successfully completing 5 years of adjuvant tamoxifen. The use of tamoxifen beyond 5 years is not recommended, but the need to protect against relapse following tamoxifen is clear. The third-generation aromatase inhibitors offer a new approach to treating postmenopausal women with receptor-positive early stage breast cancer through the potent and specific systemic inhibition of estrogen synthesis. ⋯ Letrozole showed minimal side effects compared with placebo; adverse effects on bone metabolism of uncertain clinical significance were the most noteworthy side effect. Thus, the updated results from the MA.17 trial support the previous findings and show extended adjuvant therapy with letrozole to be a well-tolerated protection against the continuing risk of breast cancer recurrence for thousands of women currently receiving standard adjuvant tamoxifen. The re-randomization of MA.17 patients to an additional 5 years of letrozole or to no treatment will provide further insights into the benefits and side effects of long-term treatment.
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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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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 · Apr 2006
Randomized Controlled Trial Multicenter StudyThe use of early adjuvant aromatase inhibitor therapy: contributions from the BIG 1-98 letrozole trial.
Letrozole has proven efficacious in a variety of therapeutic scenarios, including that of extended adjuvant therapy following 5 years of tamoxifen treatment in postmenopausal women with estrogen-receptor-positive early breast cancer. The Breast International Group 1-98 trial (BIG 1-98) is the first to study the efficacy of upfront letrozole treatment and the first to evaluate the benefits of initial versus sequential aromatase inhibitor therapy. At 25.8 months of follow-up, the primary core analysis of BIG 1-98 compared the efficacy of upfront letrozole treatment with that of upfront tamoxifen treatment in 8,010 postmenopausal women with early breast cancer. ⋯ Letrozole has an efficacy advantage over tamoxifen and can now be considered part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer. Women at increased risk for recurrence may obtain protective benefit from letrozole. Letrozole is generally well tolerated and is associated with a similar frequency of serious side effects, but fewer deaths, than tamoxifen.
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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.