Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). © 2019 American Society for Bone and Mineral Research.

NCCN Guidelines Insights: Antiemesis, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine.

Managing cancer treatment-induced bone loss and osteoporosis in patients with breast or prostate cancer.

PURPOSE: To discuss trends in breast and prostate cancer prevalence and survival; risk factors for bone loss, osteoporosis, and fractures and the approach to risk assessment in patients with these malignancies; established and investigational drug therapies for managing cancer treatment-induced bone loss and osteoporosis; and the role of health-system pharmacists in promoting bone health in patients with breast or prostate cancer. SUMMARY: Breast cancer and prostate cancer are common, deadly diseases, but many survivors are alive today because of improvements in early detection and treatment over the past 10-15 years. Cancer chemotherapy, corticosteroids, hormone-ablation therapy, and other common risk factors place patients with breast or prostate cancer at high risk for bone loss, osteoporosis, and fractures. Most patients with breast or prostate cancer should undergo assessment of risk for bone loss and osteoporosis that involves a bone-related history and physical examination, dual-energy X-ray absorptiometry scanning, and the FRAX fracture risk assessment tool from the World Health Organization. A recent National Comprehensive Cancer Network task force report on bone health in cancer care provides recommendations for considering the use of pharmacologic therapy on the basis of the results of this assessment. Bisphosphonates are useful for slowing or preventing bone loss associated with hormone-ablation therapy in women with breast cancer and men with prostate cancer, although fracture data are limited in women and not available in men. The usefulness of other therapies (selective estrogen receptor modulators, teriparatide, calcitonin salmon, and estrogens) is limited by adverse effects, a lack of experience with the drugs in these patient populations, or both. Various drug therapies are in development for managing cancer treatment-induced bone loss and osteoporosis. The agent closest to approval by the Food and Drug Administration, denosumab, has been shown to improve bone mineral density in women and men receiving hormone-ablation therapy for breast or prostate cancer, but additional data are needed to dispel safety concerns that could limit the use of this drug in these patient populations. Health-system pharmacists play an important role in screening patients with a history of breast or prostate cancer for bone loss or osteoporosis, making drug therapy recommendations to address the problem, and counseling patients on modifiable risk factors for osteoporosis and proper use of drug therapies to improve bone health. CONCLUSION: Health-system pharmacists can improve the detection and management of cancer treatment-induced bone loss and osteoporosis in patients receiving systemic therapy for breast or prostate cancer.

The epothilones: how pharmacology relates to clinical utility.

OBJECTIVE: To review the pharmacologic properties of a novel class of chemotherapeutic agents, the epothilones, and to summarize findings from recent clinical trials investigating the various epothilones in cancer therapy. DATA SOURCES: Literature searches were conducted using MEDLINE, PubMed, and the abstract search engines for the American Society of Clinical Oncology and American Association for Cancer Research annual meetings (all searches through November 2008). Primary search terms included epothilone, BMS-247550, ixabepilone, EPO906, patupilone, sagopilone, and ZK-EPO. STUDY SELECTION AND DATA EXTRACTION: Publications were given priority for inclusion if they discussed structural or pharmacologic properties of the epothilones as a class or if they included preclinical or clinical data for epothilones currently in clinical development. DATA SYNTHESIS: The epothilones are a novel class of microtubule-stabilizing agents (MSAs). Epothilones are structurally and pharmacologically distinct from taxanes, but the exact ways in which the pharmacophores of the 2 classes differ has not been firmly established. A number of natural, semisynthetic, and fully synthetic epothilones are in various stages of clinical development. These agents differ from each other and from existing MSAs; these differences influence potency, stability, and solubility. Ixabepilone is currently approved to treat multidrug-resistant metastatic breast cancer and has demonstrated efficacy in earlier stages of breast cancer and in several other tumor types. Patupilone and sagopilone are currently under clinical investigation and have each shown promise in a number of treatment settings and tumor types. All 3 agents appear to be associated with manageable toxicities, but no class-wide toxicity profile exists for the epothilones and dose-limiting toxicities differ among the agents. CONCLUSIONS: The epothilones have demonstrated significant potential for addressing the growing therapeutic challenge of taxane resistance, and the ever-increasing pool of information regarding structure-activity relationships of these MSAs will help to optimize microtubule-targeted chemotherapy.

Treatment-experienced breast cancer.

PURPOSE: Breast cancer, the second leading cause of cancer mortality among women in the U.S., following lung cancer is described and the number of treatment options for patients with breast cancer, which has been accompanied by a trend toward declining cancer mortality, is reviewed. SUMMARY: Despite these advances in cancer therapy, many patients with early stage breast cancer eventually progress to metastatic disease. Several prognostic factors have been identified for patients with metastatic breast cancer, including tumor volume and location, comorbid conditions, response to prior therapy, and the presence of molecular tumor markers (e.g., estrogen receptors [ER] and human epidermal growth factor receptor 2 [HER2]). Metastatic breast cancer is usually incurable, and the goals of therapy are palliation of symptoms, extending survival, and improving quality of life. Options for the medical management of metastatic breast cancer include endocrine therapy, cytotoxic chemotherapy, and targeted biologic agents. Treatment guidelines developed by the National Comprehensive Cancer Network generally recommend endocrine therapy for patients with ER-positive or progesterone receptor (PR)-positive disease, for patients with bone or soft tissue metastasis, or those with asymptomatic visceral disease. Cytotoxic chemotherapy alone is usually recommended for patients with ER-negative/PR-negative disease, who have symptomatic visceral disease, or whose tumors are HER2-negative or rapidly growing. Biologic agents (e.g., trastuzumab and lapatinib) alone or in combination are recommended for patients with HER2-positive disease. CONCLUSION: Treatment options for meta-static breast cancer continue to increase as new antitumor medications enter clinical practice and controlled clinical trials evaluate the optimal combinations of established and novel medications.

Dietary supplements in patients with cancer: risks and key concepts, part 2.

PURPOSE: The risks and key concepts regarding the use of dietary supplements in patients with cancer are described. SUMMARY: There are six common characteristics of dietary supplements that must be addressed when used by patients with cancer. Clinicians must establish if the supplement is an antioxidant, is an anticoagulant or procoagulant, has immunosuppressive or immunomodulating properties, has hormonal properties, has known safety issues, and has known or theoretical drug interactions. These six characteristics of the dietary supplements commonly used by patients with cancer are reviewed to aid in the analysis of the scientific data and communication of the results with the patient or family members. A framework upon which clinicians can adequately help patients make informed decisions regarding the use of complimentary and alternative medicine and dietary supplements is also described. When evaluating the appropriateness of a supplement for use by a patient with cancer, clinicians must conduct a safety review (evaluate the six characteristics). If the supplement is considered safe, an efficacy review must be conducted, after which the clinicians can recommend the supplement's use, accept the patient's decision to use the supplement if no or inconclusive evidence exists, or discourage use if there is conclusive evidence supporting inefficacy. Available resources for locating information regarding dietary supplements are also discussed. CONCLUSION: Counseling patients with cancer about dietary supplements requires a systematic thought process that considers the available theories and data, as well as the patients' views about the agents.

Dietary supplements in patients with cancer: risks and key concepts, part 1.

PURPOSE: The risks and key concepts regarding the use of dietary supplements in patients with cancer are described. SUMMARY: There are six common characteristics of dietary supplements that must be addressed when used by patients with cancer. Clinicians must establish if the supplement is an antioxidant, is an anticoagulant or procoagulant, has immunosuppressive or immunomodulating properties, has hormonal properties, has known safety issues, and has known or theoretical drug interactions. These six characteristics of the dietary supplements commonly used by patients with cancer are reviewed to aid in the analysis of the scientific data and communication of the results with the patient or family members. A framework upon which clinicians can adequately help patients make informed decisions regarding the use of complimentary and alternative medicine and dietary supplements is also described. When evaluating the appropriateness of a supplement for use by a patient with cancer, clinicians must conduct a safety review (evaluate the six characteristics). If the supplement is considered safe, an efficacy review must be conducted, after which the clinicians can recommend the supplement's use, accept the patient's decision to use the supplement if no or inconclusive evidence exists, or discourage use if there is conclusive evidence supporting inefficacy. Available resources for locating information regarding dietary supplements are also discussed. CONCLUSION: Counseling patients with cancer about dietary supplements requires a systematic thought process that considers the available theories and data, as well as the patients' views about the agents.

Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience.

PURPOSE: To evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) -overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX). PATIENTS AND METHODS: Among 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF). RESULTS: The median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up. CONCLUSION: The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.

Cancer-treatment-induced bone loss, part 2.

PURPOSE: The pathophysiology, frequency, sequelae, diagnosis, and treatment of cancer-treatment-induced bone loss (CTIBL) are discussed. SUMMARY: CTIBL is a long-term complication associated with cancer therapies that can directly or indirectly affect bone metabolism. Although CTIBL can occur in any patient receiving a cancer therapy known to cause bone loss, CTIBL is most common in patients with breast or prostate cancer who receive chemotherapy, hormone therapy, or surgical castration, as these can cause hypogonadism and induce bone loss. CTIBL causes bone fragility and an increased susceptibility to fractures; therefore, prevention, early diagnosis, and treatment of CTIBL are essential to decrease the risk of fracture. Bone loss occurs more rapidly and tends to be more severe in patients with CTIBL compared with those with normal age-related bone loss. Fractures of the hip, vertebra, and wrist are the fractures most commonly associated with bone loss. CTIBL is diagnosed by measuring bone mass using bone densitometry. Treatment of CTIBL consists of changing diet and lifestyle such as optimizing calcium and vitamin D intake, exercising, modifying behaviors known to increase the risk of CTIBL and pharmacologic therapy with hormone replacement therapy (HRT), selective estrogen-receptor modifiers (SERMs), calcitonin, or a bisphosphonate. CONCLUSION: Early identification and treatment of CTIBL are essential to prevent fractures. Patients should be instructed to optimize calcium and vitamin D intake, exercise regularly, and modify lifestyle behaviors known to cause bone loss. Patients with CTIBL should be treated with an oral or i.v. bisphosphonate; SERMs or HRT may be an option in some patients if contraindications do not exist.

Cancer-treatment-induced bone loss, part 1.

PURPOSE: The pathophysiology, frequency, sequelae, diagnosis, and treatment of cancer-treatment-induced bone loss (CTIBL) are discussed. SUMMARY: CTIBL is a long-term complication associated with cancer therapies that can directly or indirectly affect bone metabolism. Although CTIBL can occur in any patient receiving a cancer therapy known to cause bone loss, CTIBL is most common in patients with breast or prostate cancer who receive chemotherapy, hormone therapy, or surgical castration, as these can cause hypogonadism and induce bone loss. CTIBL causes bone fragility and an increased susceptibility to fractures; therefore, prevention, early diagnosis, and treatment of CTIBL are essential to decrease the risk of fracture. Bone loss occurs more rapidly and tends to be more severe in patients with CTIBL compared with those with normal age-related bone loss. Fractures of the hip, vertebra, and wrist are the fractures most commonly associated with bone loss. CTIBL is diagnosed by measuring bone mass using bone densitometry. Treatment of CTIBL consists of changing diet and lifestyle such as optimizing calcium and vitamin D intake, exercising, modifying behaviors known to increase the risk of CTIBL and pharmacologic therapy with hormone replacement therapy (HRT), selective estrogen-receptor modifiers (SERMs), calcitonin, or a bisphosphonate. CONCLUSION: Early identification and treatment of CTIBL are essential to prevent fractures. Patients should be instructed to optimize calcium and vitamin D intake, exercise regularly, and modify lifestyle behaviors known to cause bone loss. Patients with CTIBL should be treated with an oral or i.v. bisphosphonate; SERMs or HRT may be an option in some patients if contraindications do not exist.

Efficacy of Anastrozole in a Consecutive Series of Advanced Breast Cancer Patients Treated with Multiple Prior Chemotherapies and Endocrine Agents: M. D. Anderson Cancer Center Experience.

Anastrozole is a highly selective, nonsteroidal aromatase inhibitor approved by the U.S. Food and Drug Administration (FDA) in January 1996 for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. To date, information on anastrozole's use has been limited to breast cancer patients with minimal prior therapy. The purpose of this review was to determine, in clinical practice, the benefits of anastrozole in advanced breast cancer patients treated with multiple prior cytotoxic and endocrine therapies. This was a retrospective review of a consecutive series of 117 patients who received anastrozole after marketing in January 1996. As this was not a prospective study, rigorous response criteria could not be applied. Responses were categorized as improvement in disease (ID), stable disease (SD), or progressive disease (PD). One hundred eight patients were evaluable for response with a median age of 61 years and the number of prior therapies ranging from one to nine. Response, defined as improvement of disease or stable disease >/=8 weeks, was seen in 59% of patients. Patients with three or more prior endocrine therapies demonstrated a 61% response (ID + SD) and patients with ER-negative tumors demonstrated 50% response. Patients with prior aminoglutethamide therapy exhibited similar response rates to the overall group. One male patient received anastrozole without benefit. This data determines the activity of anastrozole even in heavily pretreated patients and suggests that patients who have tumors that are ER-negative may also benefit from anastrozole therapy.