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1.
Support Care Cancer ; 23(2): 433-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25123194

RESUMO

PURPOSE: To better understand the indirect effects of standard courses of radiation therapy (RT) on distant tissue toxicity, we evaluated the frequency, course, and health and economic burden of regimen-related diarrhea in a large, multinational group of patients who were being treated for cancers of the head and neck (HNC) or lung (NSCLC). METHODS: In this exploratory, prospective study, 284 patients being treated for HNC and 60 being treated for NSCLC were stratified into four cohorts to evaluate the effect of radiation alone and radiation plus concomitant chemotherapy (CRT) on radiation-induced diarrhea (RID). RID was assessed daily throughout RT using a patient-reported five-point categorical scale. Health and resource use outcomes were evaluated at least weekly during radiation. RESULTS: Moderate to severe RID was reported in all groups and was worse among patient being treated with concomitant chemoradiation (CRT). Whereas 29 % of patients treated with radiation only developed RID, the incidence was 42 % among CRT-treated patients. Tumor site did not impact the rate of RID, but did impact the rate of development and was more acute in patients being treated for NSCLC than for HNC. Patients with significant RID had worse health and resource use outcomes than did patients without RID regardless of the form of treatment. G-tube placement, weight loss, unplanned office visits, and in-patient days were adversely affected by RID. Not surprisingly, patients treated with CRT had poorer health and resource outcomes than RT only patients, even in the absence of RID. CONCLUSION: In addition to local tissue toxicities, our results suggest that focal radiation may also be associated with significant distant tissue-centric injury here represented by RID. While these changes were seen with radiation alone, the addition of chemotherapy increased the incidence and burden of illness. RID adversely impacted resource use. This unanticipated finding supports the hypothesis that focal radiation therapy results in pathobiological changes that extend beyond the radiation field and which can produce distant changes.


Assuntos
Diarreia , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Lesões por Radiação , Erros de Configuração em Radioterapia , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Protocolos Clínicos , Diarreia/etiologia , Diarreia/prevenção & controle , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Órgãos em Risco , Estudos Prospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica/normas , Erros de Configuração em Radioterapia/efeitos adversos , Erros de Configuração em Radioterapia/prevenção & controle , Resultado do Tratamento , Estados Unidos
2.
Support Care Cancer ; 23(10): 2917-23, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25724407

RESUMO

PURPOSE: This study aims to compare the efficacy and safety of oral palonosetron with intravenous (IV) palonosetron for the prevention of cisplatin-related chemotherapy-induced nausea and vomiting (CINV). METHODS: A multinational, randomized, double-blind study enrolling adult chemotherapy-naive patients with malignant solid tumors scheduled to receive cisplatin-based highly emetogenic chemotherapy (HEC). Patients received oral palonosetron (0.50 mg) or IV palonosetron (0.25 mg), each with oral dexamethasone. The primary objective was to demonstrate non-inferiority in terms of patients with a complete response (CR, no emesis/no rescue medication) within the acute phase (0-24 h after chemotherapy administration). RESULTS: Of the 743 patients randomized, 739 received study medications and 738 were included in the full analysis set. The CR rate in the acute phase was high for both groups (oral 89.4 %; IV 86.2 %). As this difference in proportions (stratum-adjusted Cochran-Mantel-Haenszel method) was 3.21 % (99 % confidence interval (CI) -2.74 to 9.17 %), non-inferiority was demonstrated (since the lower limit of the 99 % CI was closer to zero than the predefined margin of 15 %). Treatment-emergent adverse events (TEAEs) related to the study drug were rare (oral 3.2 %; IV 6.5 %). No TEAEs related to study drug leading to discontinuation were reported. CONCLUSION: Non-inferiority of oral versus IV palonosetron was demonstrated. The CR rate in the acute phase was >86 % in both patient groups. The safety profiles were comparable.


Assuntos
Cisplatino/efeitos adversos , Dexametasona/uso terapêutico , Isoquinolinas/uso terapêutico , Náusea/prevenção & controle , Neoplasias/complicações , Quinuclidinas/uso terapêutico , Vômito/prevenção & controle , Administração Intravenosa , Administração Oral , Antieméticos/uso terapêutico , Cisplatino/farmacologia , Dexametasona/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Isoquinolinas/administração & dosagem , Isoquinolinas/farmacologia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Palonossetrom , Quinuclidinas/administração & dosagem , Quinuclidinas/farmacologia , Vômito/induzido quimicamente
3.
Support Care Cancer ; 21(5): 1453-60, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23354552

RESUMO

BACKGROUND: Palonosetron (Aloxi(®), Onicit(®)) is a pharmacologically unique 5-HT3 receptor antagonist (RA) approved as a single IV injection for the prevention of nausea and vomiting induced by chemotherapy (CINV) of either moderate or highly emetogenic potential (MEC and HEC, respectively). An oral palonosetron formulation has been developed and compared to the IV formulation. METHODS: In this multinational, multicenter, double-blind, double-dummy, dose-ranging trial, 651 patients were randomly assigned to receive one of the following as a single dose prior to moderately emetogenic chemotherapy: oral palonosetron 0.25, 0.50, and 0.75 mg or IV palonosetron 0.25 mg. Patients were also randomized (1:1) to receive dexamethasone 8 mg IV or matched placebo on day 1. The primary endpoint was complete response (CR; no emesis, no rescue therapy) during the acute phase (0-24 h). RESULTS: Acute CR rates were 73.5, 76.3, 74.1, and 70.4 % for all patients receiving the palonosetron 0.25, 0.50, and 0.75 mg oral doses, and for IV palonosetron 0.25 mg, respectively; delayed CR (24-120 h) rates were 59.4, 62.5, 60.1, and 65.4 %, and overall CR (0-120 h) rates were 53.5, 58.8, 53.2, and 59.3 %, respectively. The addition of dexamethasone improved emetic control (acute CR rate) by at least 15 % for all groups except oral palonosetron 0.25 mg, where the acute CR improvement was approximately 7 %. Adverse events were similar in nature, incidence, and intensity for all oral and IV palonosetron groups, and were the expected adverse events for 5-HT3 RAs (primarily headache and constipation). CONCLUSION: Oral palonosetron has a similar efficacy and safety profile as IV palonosetron 0.25 mg and may be the preferred formulation in certain clinical situations. Among the tested oral treatments, a palonosetron 0.50-mg oral dose has been favored for the prevention of CINV in patients receiving moderately emetogenic chemotherapy due to a numerical gain in efficacy without a side effect disadvantage.


Assuntos
Antieméticos/uso terapêutico , Isoquinolinas/uso terapêutico , Náusea/prevenção & controle , Quinuclidinas/uso terapêutico , Vômito/prevenção & controle , Administração Oral , Adulto , Idoso , Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Injeções Intravenosas , Isoquinolinas/administração & dosagem , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Palonossetrom , Quinuclidinas/administração & dosagem , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/uso terapêutico , Resultado do Tratamento , Vômito/induzido quimicamente
4.
Clin Adv Hematol Oncol ; 11(2 Suppl 1): 1-18; quiz 2 p following 18, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23598819

RESUMO

Chemotherapy-induced nausea and vomiting (CINV) is a concern for many cancer patients. It can have an enormous impact on quality of life. CINV occurring in the first 24 hours after treatment is considered acute, and CINV occurring on days 2 through 5 after treatment is considered delayed. Anticipatory nausea and depression can also occur when patients are reminded of their chemotherapy treatment. CINV can lead to weight changes, fatigue, and the need for additional medications. Even mild to moderate CINV can increase health care utilization and costs, as well as delay treatment. Nausea and vomiting are separate events, although their mechanisms are entwined. Drugs that stop vomiting do not necessarily treat nausea. Control of CINV allows patients to complete treatment and to minimize use of health care resources and additional medications. Current antiemesis agents, such as 5-hydroxytryptamine-3 (5-HT3) antagonists and neurokinin-1 (NK-1) antagonists, have markedly decreased hospitalization for chemotherapy and have nearly eliminated acute emesis. The second-generation 5-HT3 receptor palonosetron has a unique pharmacology that makes it especially effective at preventing delayed emesis.


Assuntos
Antieméticos/uso terapêutico , Isoquinolinas/uso terapêutico , Náusea/tratamento farmacológico , Piridinas/uso terapêutico , Quinuclidinas/uso terapêutico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , Vômito/tratamento farmacológico , Regulação Alostérica , Antineoplásicos/efeitos adversos , Humanos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Antagonistas dos Receptores de Neurocinina-1 , Palonossetrom , Receptores 5-HT3 de Serotonina/metabolismo , Serotonina/metabolismo , Vômito/induzido quimicamente , Vômito/prevenção & controle
5.
J Natl Compr Canc Netw ; 10(2): 149-57, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22308514

RESUMO

Despite recent progress, chemotherapy-induced nausea and vomiting (CINV), especially delayed CINV, continues to be a problem. Delayed CINV is underestimated and perceived differently by providers and patients. Communication between providers and patients about this side effect may help improve outcomes. This study identifies patients' and providers' perceptions of management and barriers to quality CINV care. Provider and patient versions of a Nausea and Vomiting Management Barriers Questionnaire were developed to address potential barriers. Providers and patients were given opportunities to add detail in open-ended questions. Providers were recruited through the NCCN and the Oncology Nursing Society mailing lists. Patients who received at least 2 cycles of chemotherapy and experienced CINV were recruited through a consortium of advocacy groups. Both providers (n = 141) and patients (n = 299) completed the survey. Providers (41%) and patients (42%) agreed medication side effects were a concern, but more patients (63%) than providers (36%) tried to limit the number of medications taken (P < .0001). Many providers (67%) spontaneously reported barriers to managing CINV, with financial and patient-related factors among the most common. Few patients (10%) reported cost as a barrier, but 37% endorsed the desire "to be strong by not complaining." Barriers to communication and quality care of CINV differ between caregivers and patients. Addressing misconceptions and establishing mutually consistent goals will lead to more effective overall care.


Assuntos
Antineoplásicos/efeitos adversos , Pessoal de Saúde/psicologia , Náusea/induzido quimicamente , Pacientes/psicologia , Percepção , Vômito/induzido quimicamente , Antieméticos/economia , Antieméticos/uso terapêutico , Atitude do Pessoal de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Náusea/economia , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Vômito/tratamento farmacológico , Vômito/economia
6.
Cancer Control ; 19(2 Suppl): 10-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22488023

RESUMO

BACKGROUND: Oncology providers frequently underestimate the incidence of chemotherapy-induced nausea and vomiting (CINV), and patients often are reluctant to report symptoms. Inadequate patient-provider communication is a significant barrier to optimal management of this debilitating toxicity. METHODS: The author reviews relevant published data and methods to optimize the clinical care of patients receiving chemotherapy with moderate-to-high emetogenic potential. RESULTS: Patient reticence plus physician expectations that patients will report symptoms accurately lead to lapses in communication and suboptimal clinical care. CONCLUSIONS: Communication strategies should serve to encourage patients to share the responsibility for establishing goals of therapy and understanding the risks and benefits of their selected antiemetic regimen, thereby becoming active participants in their own cancer care.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Náusea/terapia , Assistência Centrada no Paciente/métodos , Vômito/induzido quimicamente , Vômito/terapia , Humanos , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Vômito/tratamento farmacológico , Vômito/prevenção & controle
7.
Support Care Cancer ; 19(10): 1609-17, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20835873

RESUMO

PURPOSE: A novel transdermal formulation of granisetron (the granisetron transdermal delivery system (GTDS)) has been developed to deliver granisetron continuously over 7 days. This double-blind, phase III, non-inferiority study compared the efficacy and tolerability of the GTDS to daily oral granisetron for the control of chemotherapy-induced nausea and vomiting (CINV). PATIENTS AND METHODS: Six hundred forty-one patients were randomized to oral (2 mg/day, 3-5 days) or transdermal granisetron (one GTDS patch, 7 days), before receiving multi-day chemotherapy. The primary endpoint was complete control of CINV (no vomiting/retching, no more than mild nausea, no rescue medication) from chemotherapy initiation until 24 h after final administration. The prespecified non-inferiority margin was 15%. RESULTS: Five hundred eighty-two patients were included in the per protocol analysis. The GTDS displayed non-inferiority to oral granisetron: complete control was achieved by 60% of patients in the GTDS group, and 65% in the oral granisetron group (treatment difference, -5%; 95% confidence interval, -13-3). Both treatments were well tolerated, the most common adverse event being constipation. CONCLUSIONS: The GTDS provides effective, well-tolerated control of CINV associated with moderately or highly emetogenic multi-day chemotherapy. It offers a convenient alternative route for delivering granisetron for up to 7 days that is as effective as oral granisetron.


Assuntos
Antieméticos/uso terapêutico , Granisetron/uso terapêutico , Náusea/prevenção & controle , Vômito/prevenção & controle , Administração Cutânea , Administração Oral , Adulto , Idoso , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Preparações de Ação Retardada , Método Duplo-Cego , Feminino , Granisetron/administração & dosagem , Granisetron/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Vômito/induzido quimicamente
9.
Support Care Cancer ; 19 Suppl 1: S49-55, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21063733

RESUMO

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.


Assuntos
Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controle , Antieméticos/uso terapêutico , Pesquisa Biomédica , Relação Dose-Resposta a Droga , Vias de Administração de Medicamentos , Esquema de Medicação , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Náusea/tratamento farmacológico , Guias de Prática Clínica como Assunto , Fatores de Risco , Índice de Gravidade de Doença , Vômito/tratamento farmacológico
10.
Support Care Cancer ; 19 Suppl 1: S43-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20972805

RESUMO

Antiemetic drug development can follow the same logical path as antineoplastic drug development from appropriate preclinical models through Phase I, Phase II, and Phase III testing. However, due to the marked success of antiemetic therapy over the last 25 years, placebo antiemetic treatment against highly or moderately emetogenic chemotherapy is not acceptable. Promising antiemetic agents therefore rapidly reach Phase III testing, where they are substituted into or added to effective and accepted regimens. One challenge of antiemetic drug development is determining whether substitution is indeed acceptable or whether prior regimens must be maintained intact as a basis for further antiemetic drug development. An additional challenge is the classification of emetogenic level of new antineoplastic agents. Accurate reporting of emetogenicity of such antineoplastic agents in the absence of preventive antiemetic treatment may not be available. However, at the 2009 Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Medical Oncology (ESMO) Consensus Conference, an expert panel used best available data to establish rankings of emetogenicity. Oral chemotherapeutic agents are ranked separately from intravenous agents, recognizing intrinsic differences in emetogenicity as well as differing schedules of administration. Since oral chemotherapeutic agents are often administered in extended regimens, the distinction between acute and delayed emesis is less clear, and cumulative emesis must be considered. As control of vomiting has improved, attention has shifted to control of nausea, a related but distinct and equally important problem. Additional efforts will be necessary to understand mechanisms of nausea and to identify optimal remedies.


Assuntos
Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controle , Antieméticos/uso terapêutico , Ensaios Clínicos como Assunto , Dexametasona/administração & dosagem , Vias de Administração de Medicamentos , Esquema de Medicação , Humanos , Náusea/tratamento farmacológico , Antagonistas dos Receptores de Neurocinina-1 , Guias de Prática Clínica como Assunto , Antagonistas da Serotonina/administração & dosagem , Vômito/tratamento farmacológico
11.
Support Care Cancer ; 19 Suppl 1: S25-32, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20803039

RESUMO

In this update of our 2005 document, we used an evidence-based approach whenever possible to formulate recommendations, emphasizing the results of controlled trials concerning the best use of antiemetic agents for the prevention of emesis and nausea following anticancer chemotherapies of high emetic risk. A three-drug combination of a 5-hydroxytryptamine type 3 receptor (5-HT(3)) receptor antagonist, dexamethasone, and aprepitant beginning before chemotherapy and continuing for up to 4 days remains the standard of care. We address issues of dose, schedule, and route of administration of five selective 5-HT(3) receptor antagonists. We conclude that, for each of these five drugs, there is a plateau in therapeutic efficacy above which further dose escalation does not improve outcome. In trials designed to prove the equivalence of palonosetron to ondansetron and granisetron, palonosetron proved superior in emesis prevention, while adverse effects were comparable. Furthermore, for all classes of antiemetic agents, a single dose is as effective as multiple doses or a continuous infusion. The oral route is as efficacious as the intravenous route of administration.


Assuntos
Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controle , Dexametasona/administração & dosagem , Vias de Administração de Medicamentos , Esquema de Medicação , Humanos , Náusea/tratamento farmacológico , Antagonistas dos Receptores de Neurocinina-1 , Antagonistas da Serotonina/administração & dosagem , Vômito/tratamento farmacológico
12.
Clin Adv Hematol Oncol ; 9(11 Suppl 27): 1-14; quiz 15-6, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22362372

RESUMO

One of the most dreaded side effects of anticancer treatment, chemotherapy-induced nausea and vomiting (CINV) plays a significant role in cancer patients' morbidity and quality of life. The management of CINV has been refined over the past several decades, and CINV can now be addressed with targeted prophylactic medications aimed at inhibiting the molecular pathways involved in emesis, including serotonin receptor antagonists and neurokinin-1 receptor antagonists. Advances in the understanding of the physiology of CINV, coupled with the introduction of several agents that inhibit activation of these receptors, are reflected in current CINV guidelines. These guidelines, which are largely similar, provide recommendations based on expert review of available clinical trial data. Despite the availability of effective prophylaxis, many patients still suffer from CINV. To minimize these side effects, clinicians should ensure widespread adoption and implementation of at least 1 CINV guideline in their practice. Even when the recommendations are followed, a small group of patients continue to experience CINV, often in the form of nausea, for which few treatments are effective. Current and future studies will begin to delineate the specific pathways for the development of nausea, hopefully leading to the identification of novel agents and regimens with improved efficacy in this setting.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controle , Humanos , Guias de Prática Clínica como Assunto
13.
J Support Oncol ; 8(6): 242-51, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21265391

RESUMO

We estimated the cost-utility of palonosetron-based therapy compared with generic ondansetron-based therapy throughout four cycles of anthracycline and cyclophosphamide for treating women with breast cancer. We developed a Markov model comparing six strategies in which ondansetron and palonosetron are combined with either dexamethasone alone, dexamethasone plus aprepitant following emesis, or dexamethasone plus aprepitant up front. Data on the effectiveness of antiemetics and emesis-related utility were obtained from published sources. Relative to the ondansetron-based two-drug therapy, the incremental cost-effectiveness ratios for the palonosetron-based regimens were $115,490/quality-adjusted life years (QALY) for the two-drug strategy, $199,375/QALY for the two-drug regimen plus aprepitant after emesis, and $200,526/QALY for the three-drug strategy. In sensitivity analysis, using the $100,000/QALY benchmark, the palonosetron-based two-drug strategy and the two-drug regimen plus aprepitant following emesis were shown to be cost-effective in 39% and 26% of the Monte Carlo simulations, respectively, and with changes in values for the effectiveness of antiemetics and the rate of hospitalization. The cost-utility of palonosetron-based therapy exceeds the $100,000/QALY threshold. Future research incorporating the price structure of all antiemetics following ondansetron's recent patent expiration is needed.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Isoquinolinas/uso terapêutico , Quinuclidinas/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Vômito/prevenção & controle , Neoplasias da Mama/economia , Análise Custo-Benefício , Feminino , Humanos , Cadeias de Markov , Palonossetrom , Anos de Vida Ajustados por Qualidade de Vida
14.
Support Care Cancer ; 18 Suppl 1: S1-10, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20084406

RESUMO

INTRODUCTION: Chemotherapy-induced nausea and vomiting remains a significant problem for cancer patients. DISCUSSION: Patient factors such as polypharmacy, medication costs, mucositis, and depression may hinder good antiemetic control, while high workloads, poor communication, and underestimation of the problem on the part of healthcare professionals also play a role. Improving outcomes requires accurate assessment of risk factors, use of guidelines, and better adherence to antiemetic regimens. CONCLUSION: Extended-release formulations and new delivery systems such as transdermal patches, nasal sprays, and pumps provide a new strategy that may improve patient outcomes.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Antieméticos/efeitos adversos , Antineoplásicos/uso terapêutico , Humanos , Fatores de Risco
15.
Lancet Oncol ; 10(6): 549-58, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19428297

RESUMO

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) remains a clinical management problem after treatment with highly emetogenic chemotherapy (HEC). We therefore designed and carried out a multicentre, randomised, double-blind, placebo-controlled trial to assess whether a three-drug antiemetic regimen of ondansetron, dexamethasone, and the neurokinin-1-receptor antagonist casopitant mesylate was able to prevent acute and delayed CINV events in patients naive to chemotherapy with a malignant solid tumour who were scheduled to receive cisplatin-based HEC regimens. METHODS: The study was done between Nov 6, 2006, and Oct 9, 2007, in 77 participating centres in 22 countries. All 810 patients enrolled in the trial received dexamethasone and ondansetron. Patients were randomly assigned to also receive placebo (n=269), single oral dose of casopitant mesylate (150 mg oral, n=271), or 3-day intravenous plus oral casopitant mesylate (90 mg intravenous on day 1 plus 50 mg oral on days 2 and 3, n=270). Randomisation was done using a central telephone system at the study level, because some centres were expected to recruit only a few patients during the study period. The primary endpoint was the proportion of patients achieving complete response (no vomiting, retching, or use of rescue medications) in the first 120 h after receiving HEC. Efficacy analysis was done on the modified intention-to-treat population (n=800), which included all patients who received placebo or study drug and HEC (n=265 control, n=266 single-dose oral casopitant mesylate, n=269 3-day intravenous and oral casopitant mesylate). Safety was reported in 802 patients who received either placebo or study medication. This study is registered with ClinicalTrials.gov, NCT00431236. FINDINGS: Significantly more patients in each casopitant group achieved complete response in cycle 1 of HEC treatment than did those in the control group (175 [66%] patients in the control group, 228 [86%] in the single-dose oral casopitant mesylate group [p<0.0001 vs control], and 214 [80%] in the 3-day intravenous plus oral casopitant mesylate group (p=0.0004 vs control]). This improvement was sustained over multiple cycles of HEC. Adverse events occurred in 205 (77%) patients in the single-dose oral casopitant mesylate group and 203 (75%) patients in the 3-day intravenous and oral casopitant mesylate group compared with 194 (73%) of patients in the control group. The most common serious adverse events were neutropenia (n=5 [3%] in the control group, n=3 [1%] in the single-dose oral casopitant mesylate group, and n=11 [4%] in the 3-day intravenous plus oral casopitant mesylate group), febrile neutropenia (n=1 [<1%] in the control group, n=4 [1%] in the single-dose oral casopitant mesylate group, and n=6 [2%] in the 3-day intravenous plus oral casopitant mesylate group), and dehydration (n=4 [2%] in the control group, n=2 [<1%] in the single-dose oral casopitant mesylate group, and n=1 [<1%] in the 3-day intravenous plus oral casopitant mesylate group). INTERPRETATION: A three-drug regimen including a single oral dose or 3-day intravenous plus oral regimen of casopitant mesylate plus dexamethasone and ondansetron significantly reduced CINV events in patients receiving HEC compared with a two-drug regimen of dexamethasone and ondansetron. FUNDING: GlaxoSmithKline.


Assuntos
Antieméticos/uso terapêutico , Cisplatino/uso terapêutico , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Antagonistas dos Receptores de Neurocinina-1 , Piperazinas/uso terapêutico , Piperidinas/uso terapêutico , Vômito/prevenção & controle , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Bombas de Infusão , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Náusea/induzido quimicamente , Piperazinas/administração & dosagem , Piperidinas/administração & dosagem , Vômito/induzido quimicamente , Adulto Jovem
16.
Support Care Cancer ; 17(4): 405-11, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18762991

RESUMO

GOALS OF WORK: This study investigated physician's attitudes toward the relative importance of chemotherapeutic and antiemetic efficacy in different clinical scenarios. MATERIALS AND METHODS: Oncologists in the USA and four European countries completed an online stated-choice survey consisting of three hypothetical treatment choices for each of two patient types. Each hypothetical treatment alternative included both chemotherapy and antiemetic regimens. The two hypothetical patient types were (1) a 48-year-old woman with locoregional infiltrating ductal carcinoma of the breast and (2) a 78-year-old man with squamous cell carcinoma of the lung and multiple liver metastases. In each choice question, oncologists were asked to select the better combination of chemotherapy and antiemetic prophylaxis between two treatment alternatives. MAIN RESULTS: Five hundred fifty-seven oncologists completed the survey. For the adjuvant breast cancer patient, the most aggressive chemotherapy is consistently the most important treatment consideration in all countries. For the advanced lung cancer patient, the most aggressive chemotherapy, the less aggressive chemotherapy, and the most aggressive antiemetic prophylaxis are of similar importance in most countries. CONCLUSIONS: Physicians appear more likely to prescribe a more aggressive chemotherapy regimen for a younger patient with a perceived curable tumor, regardless of the emetogenic properties of the chemotherapy. Symptom management is more of a concern and chemotherapeutic efficacy relatively less of a priority in an older patient with advanced disease for whom chemotherapy is not curative.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Fatores Etários , Idoso , Antineoplásicos/efeitos adversos , Coleta de Dados , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/patologia , Médicos/psicologia , Prognóstico , Estados Unidos
17.
Support Care Cancer ; 17(5): 589-94, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19037667

RESUMO

PURPOSE: Chemotherapy-induced nausea and vomiting includes both Acute (0-24 h) and Delayed (24-120 h) components with different physiologic mechanisms. A combination of a serotonin antagonist, a corticosteroid, and an NK-1 antagonist has proven effective against this problem. However, standard antiemetic regimens require administration over 3-4 days after chemotherapy. The present study evaluated a more convenient single-day three-drug antiemetic regimen for patients receiving moderately emetogenic chemotherapy. MATERIALS AND METHODS: Chemotherapy-naïve patients with solid tumors receiving cyclophosphamide and/or doxorubicin were eligible. Patients could not have pre-existing etiologies for vomiting. Prior to chemotherapy, patients received a single dose of aprepitant 285 mg p.o., dexamethasone 20 mg p.o., and palonosetron 0.25 mg i.v. A daily patient diary recording episodes of emesis and severity of nausea was then kept for 5 days. Any further antiemetics were considered rescue medication. RESULTS: Forty-one eligible and evaluable patients (40 women, one man) with breast cancer were entered on study. Most were receiving adjuvant chemotherapy. Complete Response (no vomiting, no rescue medication) was seen in 51% of patients, including 76% with Complete Response for the Acute period and 66% for the Delayed period. No emesis was reported for 100% of patients in the Acute period and 95% in the Delayed period. No Nausea was seen in 32% of patients. No untoward toxicities were seen. CONCLUSION: A single-day three-drug antiemetic regimen is feasible and effective for protection against both Acute and Delayed vomiting after moderately emetogenic chemotherapy. Formal comparison to a standard multi-day antiemetic regimen is warranted.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/prevenção & controle , Vômito/prevenção & controle , Adulto , Idoso , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Antineoplásicos/uso terapêutico , Aprepitanto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama Masculina/tratamento farmacológico , Quimioterapia Adjuvante/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversos , Isoquinolinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Morfolinas/uso terapêutico , Náusea/induzido quimicamente , Palonossetrom , Quinuclidinas/administração & dosagem , Quinuclidinas/efeitos adversos , Quinuclidinas/uso terapêutico , Fatores de Tempo , Vômito/induzido quimicamente
18.
Lung Cancer ; 57(3): 410-3, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17475364

RESUMO

As the number of long-term cancer survivors increases, secondary malignancies are becoming a greater clinical issue. Although some of these malignancies may be related to common environmental exposures, a significant number are considered to be therapy-related. Pleural malignant mesothelioma is a neoplasm that may be related to asbestos exposure or radiation exposure. Previous reports of pleural mesothelioma as a second malignancy have tended to follow radiotherapy for extra-thoracic malignancies such as Hodgkin's disease, breast cancer and Wilms' tumor. We report the case of a 66-year-old woman with no prior asbestos exposure who developed pleural mesothelioma 17 years after pneumonectomy and adjuvant radiation therapy for non-small cell lung cancer. Opacification of the lung field from prior therapy made determination of the diagnosis more challenging. Secondary malignancies such as mesothelioma should be considered in patients who develop unexplained symptoms even long after treatment of a primary tumor.


Assuntos
Neoplasias Pulmonares/radioterapia , Mesotelioma/diagnóstico , Neoplasias Induzidas por Radiação/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias Pleurais/diagnóstico , Adolescente , Adulto , Feminino , Humanos , Masculino , Mesotelioma/etiologia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Neoplasias Pleurais/etiologia
20.
Clin Adv Hematol Oncol ; 5(12 Suppl 19): 1-20, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18277964

RESUMO

A Review of a Satellite Symposium Held in Conjunction With the 14th European Conference of Clinical Oncology, September 23-27, 2007, Barcelona, Spain.

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