Seminars in oncology
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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
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 · 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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Although rare, cardiotoxicity is a significant complication of cancer treatment. The incidence and severity of cardiotoxicity are dependent on the type of drugs used, dose and schedule employed, and age of patients, as well as the presence of coexisting cardiac diseases and previous mediastinal irradiation. Anthracyclines are among one of the most active agents in oncology, but their use is often hampered by their cumulative dose-limiting cardiotoxicity. ⋯ Existing methods of minimizing cardiotoxicity include the use of protective agents such as dexrazoxane, different preparations of anthracyclines such as liposomal formulations, and alternative scheduling techniques. Assessment of left ventricular ejection fraction (LVEF) with two-dimensional (2D)-echocardiography or radionuclide ventriculography (RNVG) remains the most pragmatic means of monitoring for cardiotoxicity. The increasing number of long-term survivors of pediatric cancers, as well as the use of trastuzumab, taxanes, and anthracyclines in adjuvant treatment of breast cancer, means that more than ever, cardiotoxicity will remain an important issue for clinicians.