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Coleman R.,Yorkshire Cancer Research | Body J.J.,Free University of Colombia | Aapro M.,Multidisciplinary Oncology Institute | Hadji P.,University of Marburg | Herrstedt J.,University of Southern Denmark
Annals of Oncology | Year: 2014

There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling. This endocrine disturbance results in accelerated bone loss and an increased risk of osteoporosis and fractures that can have a significant negative impact on the lives of the rapidly expanding number of long-term cancer survivors. Finally, the bone marrow micro-environment is also intimately involved in the metastatic processes required for cancer dissemination, and there are emerging data showing that, at least in some clinical situations, the use of bone-targeted treatments can reduce metastasis to bone and has potential impact on patient survival. © The Author 2014.


Aapro M.,Multidisciplinary Oncology Institute | Andre F.,University Paris - Sud | Andre F.,Institute Gustave Roussy | Blackwell K.,Duke University | And 6 more authors.
Annals of Oncology | Year: 2014

Background: Everolimus, an orally administered rapamycin analogue, inhibits the mammalian target of rapamycin (mTOR), a highly conserved intracellular serine-threonine kinase that is a central node in a network of signaling pathways controlling cellular metabolism, growth, survival, proliferation, angiogenesis, and immune function. Everolimus has demonstrated substantial clinical benefit in randomized, controlled, phase III studies leading to approval for the treatment of advanced renal cell carcinoma,advanced neuroendocrine tumors of pancreatic origin, renal angiomyolipoma and subependymalgiant-cell astrocytoma associated with tuberous sclerosis complex, as well as advanced hormone-receptorpositive (HR+) and human epidermal growth factor receptor-negative advanced breast cancer. Materials and methods: We discuss clinically relevant everolimus-related adverse events from the phase III studies, including stomatitis,noninfectious pneumonitis,rash, selected metabolic abnormalities, and infections,with focus on appropriate clinical management of these events and specific considerations in patients with breast cancer.Results: The majority of adverse events experienced during everolimus therapy are of mild to moderate severity. The safety profile and protocols for toxicity management are well established. The class-effect adverse event profile observed with everolimus plus endocrine therapy in breast cancer is (as expected) distinct from that of endocrine therapy alone,but is similar to that observed with everolimus in other solid tumors. Information gained from the experience in other carcinomas on prompt diagnosis and treatments to optimize drug exposure,treatment outcomes,and patients' quality of life also applies to the patient population with advanced breast cancer.Conclusions: As with all orally administered agents, education of both physicians and patients in the management of adverse events for patients receiving everolimus is critical to achieving optimal exposure and clinical benefit.Active monitoring for early identification of everolimus-related adverse events combined with aggressive and appropriate intervention should lead to a reduction in the severity and duration of the event. © The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Droz J.-P.,University Claude Bernard Lyon 1 | Aapro M.,Multidisciplinary Oncology Institute | Balducci L.,H. Lee Moffitt Cancer Center and Research Institute | Boyle H.,University Claude Bernard Lyon 1 | And 15 more authors.
The Lancet Oncology | Year: 2014

In 2010, the International Society of Geriatric Oncology (SIOG) developed treatment guidelines for men with prostate cancer who are older than 70 years old. In 2013, a new multidisciplinary SIOG working group was formed to update these recommendations. The consensus of the task force is that older men with prostate cancer should be managed according to their individual health status, not according to age. On the basis of a validated rapid health status screening instrument and simple assessment, the task force recommends that patients are classed into three groups for treatment: healthy or fit patients who should have the same treatment options as younger patients; vulnerable patients with reversible impairment who should receive standard treatment after medical intervention; and frail patients with non-reversible impairment who should receive adapted treatment. © 2014 Elsevier Ltd.


Olver I.,Cancer Council Australia | Molassiotis A.,University of Manchester | Aapro M.,Multidisciplinary Oncology Institute | Herrstedt J.,University of Southern Denmark | And 2 more authors.
Supportive Care in Cancer | Year: 2011

Purpose and methods: As a part of reviewing the Multinational Association of Supportive Care in Cancer (MASCC) antiemetic guidelines in Perugia in 2009, an expert group identified directions for future antiemetic research. Results and conclusions: In future trials, the prediction of nausea and vomiting may combine algorithms based on observed prognostic factors relating to the patient and the anticancer therapy, the identification of the genes that code for receptors, and pharmacogenetic studies of the metabolism of drugs. Design issues for future trials include standardising the emetic stimulus across studies and finding the minimum tolerated effective dose and schedule of an antiemetic. Also control of delayed emesis is not independent of the control of acute emesis. The full range of side effects and the impact on global quality of life scores should be part of the routine assessment of an antiemetic. With current high rates of control of acute vomiting, future trials will need to consider new primary endpoints such as nausea, a complex symptom, where improvement is needed. Economic endpoints should be incorporated to ascertain the cost benefit of antiemetic prophylaxis, taking into account the impact of nausea on work capacity. New antiemetic drugs may be targeted at different receptors, such as opioid, cannabinoid and peptide YY receptors. New research is needed into determining the extent of corticosteroid use. The emetic potential of a range of newer cytotoxics particularly when used in combinations and different scheduling, such as prolonged oral dosing of cytotoxics and use of targeted therapies, are all areas in need of research. More antiemetic studies are needed in niche areas such as in patients receiving high dose chemotherapy, radiation therapy or combined modality therapy. Further evidence of the efficacy of newer antiemetic agents is required in children. © 2010 Springer-Verlag.


Celio L.,Instituto Nazionale Tumori | Bonizzoni E.,University of Milan | Bajetta E.,Instituto Of Oncologia | Sebastiani S.,Helsinn Healthcare SA | And 2 more authors.
Supportive Care in Cancer | Year: 2013

Purpose: Data from two randomized trials, evaluating a single-day regimen of palonosetron plus dexamethasone against emesis due to moderately emetogenic chemotherapy, were assessed for the impact of age on outcome in a pooled sample of women receiving anthracycline and/or cyclophosphamide (AC)-containing chemotherapy. Methods: Chemo-naïve breast cancer patients randomized to receive palonosetron (0.25 mg) plus dexamethasone (8 mg IV) on day 1 of chemotherapy (n = 200), or the same regimen followed by oral dexamethasone (8 mg) on days 2 and 3 (n = 205), were included in the analysis. The primary endpoint was complete response (CR: no vomiting and no rescue anti-emetics) in the 5-day study period. The effect of the 1-day regimen and age (<50 and ≥50 years) was investigated by a meta-analysis of individual patient data. Results: Younger patients comprised 43 % and 49 % of the 1-day and 3-day regimen groups, respectively; 94 % of the pooled sample received the AC combination. There were no between-treatment differences in CR rate according to age during all observation periods. In the 1-day regimen group, 55.2 % of younger patients achieved overall CR compared with 54 % of older patients. In the 3-day regimen group, 51.5 % of younger patients achieved overall CR compared with 58.7 % of older patients. In the adjusted analysis, younger age was not associated with overall CR to treatment (risk difference, -3.1 %; 95 % CI, -13.0 to 6.7 %; P = 0.533). Conclusions: These results provide evidence that, irrespective of age, the dexamethasone-sparing regimen is not associated with a significant loss in overall anti-emetic protection in women undergoing AC-containing chemotherapy. © 2012 The Author(s).


Biganzoli L.,Nuovo Ospedale Santo Stefano Instituto Toscano Tumori | Aapro M.,Multidisciplinary Oncology Institute | Loibl S.,German Breast Group | Wildiers H.,University Hospitals Leuven | Brain E.,Institute Curie Hopital Rene Huguenin
Cancer Treatment Reviews | Year: 2016

Along with anthracyclines, taxanes are the most active cytotoxics in breast cancer (BC). Balancing efficacy against toxicity in older patients with reduced physiological reserves and significant comorbidities is both important and difficult. This is especially so given the under-representation of elderly patients in major trials and a consequent lack of evidence for drug, dose and schedule. However, BC is frequent in elderly women, who are a growing proportion of the population. Careful consideration of their care is therefore imperative. Treatment that can cure or extend the duration and quality of life should not be restricted by age, but needs to be tailored to the circumstances of elderly patients. In adjuvant use, taxane toxicity in older women is greater than in their younger counterparts, limiting its sequential combination with anthracyclines for high-risk disease unless patients are in very good health. More frequently taxanes are used alone (weekly paclitaxel, three-weekly docetaxel) or combined with cytotoxics other than anthracyclines (e.g. docetaxel plus cyclophosphamide) to reduce cardiac risk, especially in HER-2-positive patients who may develop additional trastuzumab-related cardiac events. In elderly patients with metastases, weekly paclitaxel and three-weekly docetaxel are among the cornerstones of treatment, with generally acceptable toxicity. Three-weekly docetaxel at the approved dose of 100 mg/m2 is not appropriate for the elderly. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication but has been little studied in older BC patients. A head-to-head comparison with weekly paclitaxel favoured the solvent-free formulation for pathologic response, but those studied were a general adult population. Compared with early stage disease, choice of taxane and regimen in the metastatic setting relies even more on availability and preferences with regard to schedule, toxicity profile and cost, especially for recently developed formulations. © 2015 Elsevier Ltd.


Aapro M.,Multidisciplinary Oncology Institute | Wildiers H.,University Hospitals Leuven
Annals of Oncology | Year: 2012

Breast cancer in advanced age has been associated with a slightly increased probability of favourable tumour biology (e.g. hormone receptor-positive and human epidermal growth factor-2 [HER2]-negative by immunohistochemistry). Nevertheless, a substantial proportion of older women (∼15-18%) still develop 'triple-negative' breast cancer (TNBC), which is generally associated with a poor prognosis. To date, there have been very few investigations comparing the prognosis of younger and older women with TNBC; however, some emerging studies suggest that older patients with TNBC may have a better outcome when compared with their younger counterparts. The reasons for these differences in prognosis have yet to be fully elucidated, but may be due to age-related biological variations, as suggested by observed differences in the distribution of histological subtypes of TNBC, or perhaps other unknown (biological) factors. Despite the evidence of benefit of chemotherapy in TNBC in older women, there is still a tendency for geriatric patients to receive less adjuvant chemotherapy than their younger counterparts. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Aapro M.,Multidisciplinary Oncology Institute
Hematology Reports | Year: 2011

A taskforce of the International Society of Geriatric Oncology (SIOG) has recently submitted recommendations on the use of anthracyclines in elderly patients. Despite the aging of the population and the high proportion of elderly individuals in the population of patients with non-Hodgkin's lymphoma, the development of specialist expertise in the treatment of elderly patients with cancer is relatively recent. Treatment of the elderly is complex because they are a highly heterogeneous population, with large variations in health status, comorbidities and life expectancy. In addition, these patients are generally more susceptible than young patients to the cardiotoxic effects of anthracyclines. Strategies for assessing elderly patients with cancer, reducing the risk of congestive heart failure, and assessing the cardiotoxic effects of treatments are discussed. In addition, a summary of the SIOG recommendations is presented. © M. Aapro, 2011.


Aapro M.S.,Multidisciplinary Oncology Institute
The oncologist | Year: 2012

The landscape of treatment for advanced prostate cancer is continually evolving as new therapies are developed and guidelines are constantly updated. However, the management of older men with advanced disease is not optimal. Many men are denied chemotherapy based on their chronological age, not their health status. Androgen-deprivation therapy (ADT) remains the mainstay of first-line treatment of advanced disease. Once the disease becomes resistant to castration, docetaxel-based chemotherapy is the regulatory-approved standard of care, irrespective of age. The place of weekly docetaxel in patients with poor performance status and signs of frailty has to be further evaluated in clinical studies. New treatments are now available, or on the horizon, for disease that progresses during or after docetaxel therapy. Cabazitaxel and abiraterone have been shown to prolong survival, irrespective of age, and are already in clinical use having received regulatory approval. The optimal sequence for these two agents is still unknown, although there is some indication that in patients predicted to be poor responders to abiraterone (high Gleason score, progression during docetaxel therapy, rapid progression to castrate-resistant prostate cancer with ADT) cabazitaxel should be the preferred choice. Further advances are being investigated, with promising data reported from phase III trials.


Jordan K.,Martin Luther University of Halle Wittenberg | Jahn F.,Martin Luther University of Halle Wittenberg | Aapro M.,Multidisciplinary Oncology Institute
Annals of Oncology | Year: 2015

The prevention of chemotherapy-induced nausea and vomiting (CINV) has been revolutionized over the past 25 years. Guideline-based treatment means that vomiting can be prevented in the majority, but not in all patients. Therefore, antiemetic research continues with the goal of optimizing CINV control for all patients. This comprehensive review summarizes the research efforts in this field over the past few years. Emerging from this research are two new antiemetic agents, netupitant/ palonosetron, the first antiemetic combination agent and rolapitant, a new NK1RA. In addition, studies have evaluated the benefits of olanzapine and ginger, explored optimal combinations of agents for delayed CINV prevention, confirmed that dexamethasone-sparing regimens are effective, and demonstrated the value of NK1RAs in high-dose chemotherapy settings as well as with certain moderately emetogenic chemotherapies such as carboplatin. Research has also validated the correlation between antiemetic guideline adherence and improved CINV control. Finally, regulatory authorities have utilized extreme caution in retiring some 5-HT3RAs or decreasing their maximum dose. © The Author 2015.

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