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Hadji P.,University of Marburg | Aapro M.,Institute Multidisciplinaire dOncologie | Costa L.,Institute Medicina Molecular | Gnant M.,Medical University of Vienna
Cancer Treatment Reviews | Year: 2012

Antiresorptive therapies are the standard of care for maintaining bone health in patients with advanced cancers involving bone. In the absence of antiresorptive therapies, many patients with bone metastases from solid tumors will experience potentially debilitating skeletal-related events. Furthermore, older age is associated with decreased bone integrity both in female and male patients and also with increased risk for malignancies, such as breast and prostate cancer, which have a high risk of metastasis to bone. Although antiresorptive therapies are generally well tolerated, there have been reports of associated serious adverse events. Hypocalcemia, osteonecrosis of the jaw, renal events, and acute-phase reactions have been reported in patients with cancer receiving all types of antiresorptive therapies. Because the clinical indications of antiresorptive agents continue to expand, and new options are becoming available, it is important for clinicians to recognize adverse events so that they may be prevented or properly treated and managed. Moreover, the risk-benefit profiles of those agents must be considered on a per-patient basis. © 2012 Elsevier Ltd.


Hesketh P.J.,St Elizabeths Medical Center | Aapro M.,Institute Multidisciplinaire dOncologie | Street J.C.,Reagent | Carides A.D.,Merck And Co.
Supportive Care in Cancer | Year: 2010

Goals of work Certain patient and treatment characteristics are predictive of chemotherapy-induced nausea and vomiting (CINV). Objectives of this analysis were: (1) confirm the importance of several previously reported adverse risk factors for CINV in patients receiving chemotherapy, (2) assess the impact of the NK1 receptor antagonist aprepitant according to these risk factors, and (3) assess the impact of age on antiemetic outcome. Patients and methods Patients from two double-blind, placebo-controlled trials were randomized to an activecontrol group (ondansetron 32 mg IV, dexamethasone 20 mg PO day 1; dexamethasone 8 mg bid days 2-4) or an aprepitant group (aprepitant 125 mg PO, ondansetron 32 mg IV, dexamethasone 12 mg day 1; aprepitant 80 mg days 2-3; dexamethasone 8 mg qd days 2-4). The primary endpoint was complete response (no emesis or rescue therapy use). In a post-hoc analysis, multivariate logistic regression models were used to assess the impact of treatment with aprepitant and previously reported risk factors, using a modified intent-to-treat approach. Main results Treatment with aprepitant (p<0.0001), male gender (p=0.023), cisplatin dose <80 mg/m2 (p=0.001), age ≥65 years (p=0.021), and five or more alcoholic drinks per week (p=0.027) were all significantly associated with improved complete response. Aprepitant improved complete response regardless of risk for all factors and neutralized the risk associated with female gender. Conclusions This analysis confirmed the relevance of several previously reported risk factors for CINV in patients receiving chemotherapy. Aprepitant improved complete response regardless of risk and eliminated the increased risk of CINV associated with the female gender. © Springer-Verlag 2009.


Aapro M.,Institute Multidisciplinaire dOncologie | Launay-Vacher V.,Service ICAR
Cancer Treatment Reviews | Year: 2012

Monitoring renal function in patients with solid tumors and hematologic malignancies is vital to the safe administration of therapeutic agents. Renal impairment is frequent in elderly patients (i.e., age≥65) with cancer, despite normal serum creatinine levels in most patients. Because serum creatinine levels do not accurately reflect clearance rates, renal function should be estimated by calculation (either Cockcroft-Gault or abbreviated Modification of Diet in Renal Disease [aMDRD] equations) or by measuring creatinine clearance using a 24-h urine collection. Additionally, patients with cancer often have preexisting comorbidities or other risk factors that increase the probability of renal impairment before receiving potentially nephrotoxic therapies. Patient age, preexisting renal dysfunction, and chronic comorbidities (e.g., diabetes, kidney disease, hypertension, and cardiac insufficiency) all contribute to the risk of renal impairment. Furthermore, both cancer and its therapies may lead to renal impairment. A number of cancer therapy agents are nephrotoxic, including chemotherapy agents, molecular targeted agents, pain management agents, radiopharmaceuticals, contrast agents used in radiology, and antiresorptive agents, and contrast agents used in radiology are nephrotoxic as well. Undetected decreases in clearance rates by the kidneys can greatly increase exposure to treatment agents, possibly decreasing the safety of treatment and exacerbating renal impairment. In conclusion, all cancer patients, not only those receiving potentially nephrotoxic agents, require renal monitoring. © 2011 Elsevier Ltd.


Aapro M.S.,Institute Multidisciplinaire dOncologie
Targeted Oncology | Year: 2012

Until recently, prescribers had to deal with generics, considered to be simple molecules that are easy to copy. But as discussed in this paper, the biodisponibility of generics remains a source of uncertainty. And now there are biosimilars, limited for the time being in the cancer setting to granulocyte-colony stimulating factors (G-CSFs) and epoetins. Soon there will be biosimilar monoclonal antibodies with anticancer activity. Prescribers will ask, as they did for generics, if such drugs have the same activity as originators, if their safety profile is the same, if quality of the production process is guaranteed. Prescribers will want to know if their patients are indeed receiving the prescribed product, and not another. Finally prescribers will want to check that the lower cost of biosimilars will allow them to adhere to international guidelines. This should benefit patients and the community. © 2011 Springer-Verlag.


Aapro M.S.,Institute Multidisciplinaire dOncologie
Cancer Investigation | Year: 2010

The use of endocrine therapy in breast cancer represents one of the earliest molecular targeting strategies used in cancer treatment. Tamoxifen, a selective estrogen-receptor (ER) modulator, has been the standard of care for women with receptor-positive breast cancer for the last 30 years. Tamoxifen suppresses the estrogen-dependent growth of breast cancer cells by specifically targeting the ER. Because of estrogenic effects, tamoxifen does not increase the risk of osteoporosis, but it can lead to endometrial cancer and thromboembolism. The third-generation aromatase inhibitors (AIs) exert their tumor antiproliferative action by targeting an enzyme critical for estrogen biosynthesis. The AIs thus have a different mechanism of action than tamoxifen, and a different safety profile. The majority of adverse events (AEs) related to the AIs are mild to moderate. Most of these AEs are common to menopause and are predictable and manageable. This review looks at AI-associated side effects and current clinical management strategies, with a particular emphasis on managing bone health. Compliance with long-term therapy, strategies to improve adherence, and considerations in elderly patients with hormone-responsive breast cancer are also discussed. Copyright © 2010 Informa Healthcare USA, Inc.


Aapro M.S.,Institute Multidisciplinaire dOncologie | Walko C.M.,University of North Carolina at Chapel Hill
Annals of Oncology | Year: 2010

The implications of chemotherapeutic drug-drug interactions can be serious and thus need to be addressed. This review concerns the potential interactions of the antiemetic aprepitant, a neurokinin-1 receptor antagonist indicated for use (in Europe) in highly emetogenic chemotherapy and moderately emetogenic chemotherapy (MEC) in combination with a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and corticosteroids and (in the United States) in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy including high-dose cisplatin. When considering use of aprepitant for prevention of chemotherapy-induced nausea and vomiting, its potential drug-drug interaction profile as a moderate inhibitor of cytochrome P-450 isoenzyme 3A4 (CYP3A4) has been a source of concern for some physicians and other health care professionals. We explore in this paper how real those concerns are. Our conclusion is that either no interaction or no clinically relevant interaction exists with chemotherapeutic agents (intravenous cyclophosphamide, docetaxel, intravenous vinorelbine) or 5-HT3 antagonists (granisetron, ondansetron, palonosetron). For relevant interactions, appropriate measures, such as corticosteroid dose modifications and extended International Normalized Ratio monitoring of patients on warfarin therapy, can be taken to effectively manage them. Therefore, the concern of negative interactions remains largely theoretical but needs to be verified with new agents extensively metabolized through the 3A4 pathway. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.


Aapro M.S.,Institute Multidisciplinaire dOncologie
Oncologie | Year: 2011

Until recently the prescriber had to deal with generics, considered to be simple molecules which are easy to copy. But as discussed in this paper, the biodisponibility of generics remains a source of uncertainty. And now arrive biosimilars, limited for the time being in the cancer setting to granulocyte-colony stimulating factors (G-CSFs) and epoetins. Soon there will be biosimilar monoclonal antibodies with anticancer activity. The prescriber will ask, as for generics, if such drugs have the same activity as originators, if their safety profile is the same, if quality of the production process is guaranteed. The prescriber will want to know if the patient is indeed receiving the prescribed product, and not another. Finally the prescriber will want to check that the lower cost of biosimilars will allow to adhere to international guidelines. This should benefit patients and the community. © 2011 Springer Verlag France.


Chapell R.,Merck And Co. | Aapro M.S.,Institute Multidisciplinaire dOncologie
Journal of Geriatric Oncology | Year: 2013

Background: Various antiemetic agents are commonly administered during and after chemotherapy to prevent nausea and vomiting depending on the emetogenic risk. Data specific for patients older than 65 are rarely discussed and it is often assumed that such patients have less risk of nausea and vomiting and might not need the same prevention. Objective: To determine whether response to antiemetic regimens incorporating aprepitant varies with patient age, we combined previously unpublished subgroup analyses from four previously published studies. Methods: Risk ratios were combined using standard meta-analytic techniques to determine whether antiemetic regimens including aprepitant lead to more complete responses to antiemetic therapy than regimens without aprepitant, among patients aged 65 and over. Results: Patients aged 65 and over have a significantly greater chance of experiencing a complete response (no vomiting or use of rescue therapy) to antiemetic treatment when aprepitant is included in the antiemetic regimen (Risk Ratio 1.25, 95% Confidence Interval 1.11 to 1.40, p = 0.0002) than when it is not. This risk ratio is not significantly different (Q = 0.281, p = 0.596) from the risk ratio calculated for patients under age 65 (1.30, 95% Confidence Interval 1.19 to 1.42), from the same set of studies. Limitations: This meta-analysis combines studies utilizing different antiemetic regimens and different patient populations. Only a single efficacy outcome is included, and safety is not assessed. Conclusion: We conclude that for both the under 65years and the age 65 and over populations, antiemetic regimens including aprepitant, along with a 5-HT3 antagonist and a corticosteroid, are more effective in reducing chemotherapy-induced nausea and vomiting than regimens that do not include aprepitant. © 2012 Elsevier Ltd.


Aapro M.,Institute Multidisciplinaire dOncologie | Cornes P.,University of Bristol | Sun D.,University of Arizona | Abraham I.,University of Arizona
Therapeutic Advances in Medical Oncology | Year: 2012

Objectives: To evaluate the comparative cost efficiency across the European Union G5 countries of the erythropoiesis-stimulating agents (ESAs) epoetin α (originator [Eprex] and biosimilar [Binocrit®] once weekly), epoetin β (NeoRecormon® once weekly), and darbepoetin α (Aranesp® once weekly or once every 3 weeks) under different scenarios of fixed and weight-based dosing in the management of chemotherapy-induced anemia.Methods: Direct costs of ESA treatment were calculated for one patient with cancer undergoing chemotherapy (six cycles at 3-week intervals) with ESA initiated at week 4 and continued for 15 weeks. Five scenarios were developed under fixed and weight-based dosing: continuous standard dose for 15 weeks; sustained dose escalation to 1.5× or double the standard dose at week 7, continued for 12 weeks; and discontinued dose escalation to 1.5× or double the standard dose at week 7 for a 3-week period, then 9 weeks of standard dose.Results: Under fixed dosing, the average cost of biosimilar epoetin α treatment across scenarios was €4643 (30,000 IU) or €6178 (40,000 IU). Corresponding estimates were €7168 for originator epoetin α, €7389 for epoetin β, €8299 for darbepoetin α once weekly, and €9221 for darbepoetin α once every 3 weeks. Under weight-based dosing, the average cost of biosimilar epoetin α treatment across scenarios was €4726. Corresponding estimates were €5484 for originator epoetin α, €5652 for epoetin β, and €8465 for both darbepoetin α once weekly and once every three weeks.Conclusion: Managing chemotherapy-induced anemia with biosimilar epoetin α is consistently cost efficient over treatment with originator epoetin α, epoetin β, and darbepoetin α under both fixed and weight-based dosing scenarios. © The Author(s), 2012.


Aapro M.,Institute Multidisciplinaire dOncologie | Cornes P.,Bristol Haematology and Oncology Center | Abraham I.,University of Arizona
Journal of Oncology Pharmacy Practice | Year: 2012

Objectives: This cost-efficiency analysis of the granulocyte colony-stimulating factors (G-CSF) filgrastim (originator Neupogen® and biosimilar Zarzio®) and pegfilgrastim (Neulasta®) examined against a time horizon of 1-14 days of treatment and across the European Union G5 countries (a) when, cost-wise, using Neulasta® 6 mg versus Neupogen® or Zarzio® 300 μg may be cost-saving in reducing the incidence of chemotherapy-induced febrile neutropenia; and (b) if cost-wise, treatment with Zarzio® 300 μg yields a savings advantage over Neupogen® 300 μg.Methods: Cost-efficiency analysis of the direct costs a buyer or payer would incur when purchasing or covering any of these agents for managing one patient during one cycle of chemotherapy under regimens of 1-14 days of standard filgrastim using the population-weighted average unit dose cost of each agent per their public pack cost across the European G5 countries.Results: The cost of Neupogen® treatment ranged from €128.16 (1 day) to €1794.30 (14 days), compared to €95.46 and €1336.46 for Zarzio®, thus yielding potential cost savings from €32.70 to €457.84 for the latter. Neulasta® turns cost-saving at day 12 of Neupogen® treatment. At no point over a 14-day treatment period did Neulasta® yield a savings advantage over Zarzio®.Conclusion: Prophylaxis or treatment of febrile neutropenia with Zarzio® is cost-efficient under all possible treatment scenarios relative to Neupogen® and to Neulasta®. In the absence of convincing evidence that pegfilgrastim is pharmacotherapeutically superior to standard filgrastim, there is no cost-efficiency rationale to treat with Neulasta® over Zarzio®, though there may be a small window of approximately 3 days where Neulasta® is cost-efficient over Neupogen®. Regardless, our analysis shows Zarzio® to be the most cost-efficient approach to reducing the incidence of febrile neutropenia in chemotherapy-treated patients. © The Author(s) 2011.

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