RESUMO
AIMS: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. MATERIALS AND METHODS: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. RESULTS: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (≥85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). CONCLUSIONS: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.
Assuntos
Neoplasias da Mama , Qualidade de Vida , Humanos , Feminino , Estudos Prospectivos , Quimioterapia Adjuvante/métodos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Fluoruracila , Metotrexato/uso terapêutico , Ciclofosfamida/uso terapêutico , Quimiorradioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
INTRODUCTION: SUPREMO is a phase 3 randomised trial evaluating radiotherapy post-mastectomy for intermediate-risk breast cancer. 1688 patients were enrolled from 16 countries between 2006 and 2013. We report the results of central pathology review carried out for quality assurance. PATIENTS AND METHODS: A single recut haematoxylin and eosin (H&E) tumour section was assessed by one of two reviewing pathologists, blinded to the originally reported pathology and patient data. Tumour type, grade and lymphovascular invasion were reviewed to assess if they met the inclusion criteria. Slides from potentially ineligible patients on central review were scanned and reviewed online together by the two pathologists and a consensus reached. A subset of 25 of these cases was double-reported independently by the pathologists prior to the online assessment. RESULTS: The major contributors to the trial were the UK (75%) and the Netherlands (10%). There is a striking difference in lymphovascular invasion (LVi) rates (41.6 vs. 15.1% (UK); p = <0.0001) and proportions of grade 3 carcinomas (54.0 vs. 42.0% (UK); p = <0.0001) on comparing local reporting with central review. There was no difference in the locally reported frequency of LVi rates in node-positive (N+) and node-negative (N-) subgroups (40.3 vs. 38.0%; p = 0.40) but a significant difference in the reviewed frequency (16.9 vs. 9.9%; p = 0.004). Of the N- cases, 104 (25.1%) would have been ineligible by initial central review by virtue of grade and/or lymphovascular invasion status. Following online consensus review, this fell to 70 cases (16.3% of N- cases, 4.1% of all cases). CONCLUSIONS: These data have important implications for the design, powering and interpretation of outcomes from this and future clinical trials. If critical pathology criteria are determinants for trial entry, serious consideration should be given to up-front central pathology review.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Gradação de Tumores , Variações Dependentes do Observador , Resultado do TratamentoRESUMO
A high incidence of central nervous system (CNS) metastases has been reported in patients with HER2-positive tumours receiving trastuzumab therapy for metastatic breast cancer. This study tested whether prophylactic cranial irradiation (PCI) could reduce the incidence of CNS metastases in this setting. This was a prospective, randomised phase III trial. Patients were randomised 1:1 to no PCI or PCI delivered at around 6 weeks after study entry. Cognitive function was assessed prospectively. In total, 51 patients were randomised over a 3 year period; 25 received PCI and 26 did not. The cumulative incidence of CNS metastases at 2 years was 32.4% (standard error = 9.8%) on the no PCI arm and 21.0% (standard error = 8.6%) on the PCI arm; the associated hazard ratio was 0.57 (95% confidence interval 0.18-1.74; P = 0.32). There was no evidence of cognitive dysfunction in PCI patients.
Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias da Mama/tratamento farmacológico , Irradiação Craniana , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioprevenção , Feminino , Humanos , Estudos Prospectivos , Receptor ErbB-2/biossíntese , Trastuzumab/uso terapêuticoRESUMO
The mortality from breast cancer has improved steadily over the past two decades, in part because of the increased use of more effective adjuvant therapies. Thousands of women are routinely treated with intensive chemotherapy, which can be unpleasant, is expensive and is occasionally hazardous. Oncologists have long known that some of these women may not need treatment, either because they have a low risk of relapse or because they have tumour biology that makes them less sensitive to chemotherapy and more suitable for early adjuvant endocrine therapy. There is an urgent need to improve patient selection so that chemotherapy is restricted to those patients who will benefit from it. Here we review the emerging technologies that are available for improving patient selection for chemotherapy. We describe the OPTIMA trial, which has just opened to recruitment in the UK, is the latest addition to trials in this area, and is the first to focus on the relative cost-effectiveness of alternate predictive assays.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Seleção de Pacientes , Reino UnidoRESUMO
Hypofractionated radiotherapy regimens have become increasingly popular in breast cancer, particularly in the UK and Canada. However, there are some potential problems inherent to providing such regimens, such as the concern of increased toxicity. In this article we discuss the planning and dosimetry and requirements for hypofractionated radiotherapy in breast cancer and make recommendations both for the planning process and for treatment monitoring.
Assuntos
Neoplasias da Mama/radioterapia , Fracionamento da Dose de Radiação , Planejamento da Radioterapia Assistida por Computador/normas , Neoplasias da Mama/patologia , Feminino , Humanos , RadiometriaRESUMO
More women are living with and surviving breast cancer, because of improvements in breast cancer care. Trastuzumab (Herceptin) has significantly improved outcomes for women with HER2-positive tumours. Concerns about the cardiac effects of trastuzumab (which fundamentally differ from the permanent myocyte loss associated with anthracyclines) led to the development of cardiac guidelines for adjuvant trials, which are used to monitor patient safety in clinical practice. Clinical experience has shown that the trial protocols are not truly applicable to the breast cancer population as a whole, and exclude some women from receiving trastuzumab, even though they might benefit from treatment without long-term adverse cardiac sequelae. Consequently, five oncologists who recruited patients to trastuzumab trials, some cardiologists with whom they work, and a cardiovascular lead general practitioner reviewed the current cardiac guidelines in the light of recent safety data and their experience with adjuvant trastuzumab. The group devised recommendations that promote proactive pharmacological management of cardiac function in trastuzumab-treated patients, and that apply to all patients who are likely to receive standard cytotoxic chemotherapy. Key recommendations include: a monitoring schedule that assesses baseline and on-treatment cardiac function and potentially reduces the overall number of assessments required; intervention strategies with cardiovascular medication to improve cardiac status before, during, and after treatment; simplified rules for starting, interrupting and discontinuing trastuzumab; and a multidisciplinary approach to breast cancer care.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiopatias/prevenção & controle , Monitorização Fisiológica/métodos , Algoritmos , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/fisiopatologia , Feminino , Diretrizes para o Planejamento em Saúde , Coração/fisiopatologia , Cardiopatias/etiologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/fisiopatologia , Humanos , Trastuzumab , Reino Unido , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Aromatase inhibitors (AIs) are well established in the treatment of metastatic hormone-sensitive breast cancer in postmenopausal women. Cyclooxygenase (COX)-2 inhibitors have demonstrated efficacy in reducing cancer risk in animal and human studies. In several preclinical studies, combination AI plus COX-2 inhibitor therapy has shown a synergistic antitumor effect. This review describes the utility of AI plus COX-2 inhibitor therapy and discusses the completed and ongoing clinical trials investigating treatment with the AI exemestane and the COX-2 inhibitor celecoxib in the neo-adjuvant and metastatic breast cancer settings. In general, combination therapy had comparable or better efficacy compared with AI monotherapy using the end points of progression-free survival, overall response rate, clinical benefit rate, time to progression, and duration of clinical benefit. All therapies were well tolerated. There appeared to be a beneficial impact on serum lipid levels for patients receiving combination therapy in a neo-adjuvant trial despite the known cardiovascular toxicity risk associated with COX-2 inhibitors. In conclusion, AIs plus COX-2 inhibitors have shown promising efficacy and safety for the treatment of patients with metastatic breast cancer. Careful monitoring during future trials will be necessary to accurately assess the risk-benefit ratio of combination therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/patologia , Inibidores de Ciclo-Oxigenase/administração & dosagem , Feminino , Humanos , Metástase Neoplásica , Resultado do TratamentoRESUMO
The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of bortezomib plus docetaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Forty-eight patients received up to eight 21-day cycles of docetaxel (60-100 mg m(-2) on day 1) plus bortezomib (1.0-1.5 mg m(-2) on days 1, 4, 8, and 11). Pharmacodynamic and pharmacokinetic analyses were performed in a subset of patients. Five patients experienced DLTs: grade 3 bone pain (n=1) and febrile neutropenia (n=4). The MTD was bortezomib 1.5 mg m(-2) plus docetaxel 75 mg m(-2). All 48 patients were assessable for safety and efficacy. The most common adverse events were diarrhoea, nausea, alopecia, asthenia, and vomiting. The most common grade 3/4 toxicities were neutropenia (44%), and febrile neutropenia and diarrhoea (each 19%). Overall patient response rate was 29%. Median time to progression was 5.4 months. In patients with confirmed response, median time to response was 1.3 months and median duration of response was 3.2 months. At the MTD, response rate was 38%. Pharmacokinetic characteristics of bortezomib/docetaxel were comparable with single-agent data. Addition of docetaxel appeared not to affect bortezomib inhibition of 20S proteasome activity. Mean alpha-1 acid glycoprotein concentrations increased from baseline at nearly all time points across different bortezomib dose levels. Bortezomib plus docetaxel is an active combination for anthracycline-pretreated advanced/metastatic breast cancer. The safety profile is manageable and consistent with the side effects of the individual agents.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Alopecia/induzido quimicamente , Antraciclinas/administração & dosagem , Antibióticos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Bélgica , Ácidos Borônicos/administração & dosagem , Bortezomib , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/patologia , Diarreia/induzido quimicamente , Docetaxel , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Estudos Prospectivos , Pirazinas/administração & dosagem , Espanha , Taxoides/administração & dosagem , Resultado do Tratamento , Reino Unido , Vômito/induzido quimicamenteAssuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Terapia Combinada , Feminino , Coração/efeitos da radiação , Humanos , Metástase Linfática , Mastectomia , Recidiva Local de Neoplasia , Doses de Radiação , Radioterapia Adjuvante , Fatores de Risco , Parede Torácica/efeitos da radiaçãoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Antineoplásicos/administração & dosagem , Capecitabina , Ensaios Clínicos como Assunto , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Medicina Baseada em Evidências , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , HumanosRESUMO
BACKGROUND: This was a feasibility study of the combination of Exemestane and the cyclooxygenase-2 (COX-2) inhibitor Celecoxib in advanced breast cancer. PATIENTS AND METHODS: Post-menopausal women with histologically proven, hormone receptor positive, advanced breast cancer who had progressive disease, normal blood counts, liver and renal function were eligible. Exemestane was given at a dose of 25 mg daily and Celecoxib at a dose of 400 mg bd. Responses were assessed according to RECIST criteria and toxicity was accessed according to CTC. The primary end-point was the percentage of patients who had neither discontinued therapy nor progressed at 6 months ('treatment successes'). RESULTS: Fifty-three eligible patients were enrolled. Of 30 patients with target lesions, 4 (13%) had a complete response (CR), 12 (40%) a partial response (PR) and 5 (17%) stable disease (SD). The best response in 18 of the 23 patients with no target lesions at baseline was stable disease. The clinical benefit (CR, PR+SD) for the whole group was therefore 39/53 (74%). The 'treatment success' rate was 60%. There were two non-malignant deaths which may have been associated with treatment. CONCLUSION: The combination of Exemestane and Celecoxib shows promising activity and tolerability and these results support the use of this combination in phase III clinical trials of short duration treatments.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Androstadienos/administração & dosagem , Androstadienos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Celecoxib , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Qualidade de Vida , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: Supraclavicular fossa (SCF) radiotherapy plays an important part in the adjuvant management of breast cancer but data on acute radiotherapy toxicity are lacking, particularly when differing patient treatment positions are used to allow computed tomography planning or to reduce cardiac doses. MATERIALS AND METHODS: We evaluated SCF and breast/chest wall acute skin toxicity in a cohort of 92 women with breast cancer, who were planned in a 'T'-grip (n = 72) or 90 degrees-grip (n = 20) position, while 'on treatment' and at 6 weeks. The modified Radiation Therapy Oncology Group (RTOG) criteria were used to score toxicity. Data on age, body mass index, smoking history, type of breast operation, prior chemotherapy, radiation dose, number of fields and field size were recorded and correlated with outcome. RESULTS: Maximum SCF reaction score was RTOG 2a, with no moist desquamation observed. SCF reactions were less severe compared with chest wall reactions and no worse than breast reactions. There was significant resolution of toxicity at 6 weeks. SCF radiotherapy in 'T'-grip patients was well tolerated and no worse than the 90 degees-grip group. Pain scores and sore throat occurrences were minimal. Univariate and multivariate analyses showed that smoking was associated with worsening SCF toxicity (odds ratio [OR] 2.92; P = 0.045) and delayed healing. Incremental SCF dose worsened toxicity (OR 3.65; P = 0.023). Smoking worsened breast but not chest wall toxicity. CONCLUSIONS: SCF radiotherapy was at least as well tolerated as breast radiotherapy and better tolerated than chest wall radiotherapy. The 'T'-grip position did not affect toxicity negatively. Smoking and radiation dose affected SCF toxicity.
Assuntos
Neoplasias da Mama/radioterapia , Irradiação Linfática/efeitos adversos , Lesões por Radiação/epidemiologia , Pele/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Clavícula , Relação Dose-Resposta à Radiação , Feminino , Humanos , Modelos Logísticos , Irradiação Linfática/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/etiologia , Radioterapia Adjuvante/efeitos adversos , Escócia/epidemiologia , Estatísticas não Paramétricas , Parede Torácica/efeitos da radiaçãoRESUMO
One hundred and sixteen women with measurable metastatic breast cancer participated in a randomised phase II study of single agent liposomal pegylated doxorubicin (Caelyx) given either as a 60 mg/m2 every 6 weeks (ARM A) or 50 mg/m2 every 4 weeks (ARM B) schedule. Patients were over 65 years of age or, if younger, had refused or been unsuitable for standard anthracyclines. The aims of the study were to evaluate toxicity and dose delivery with the two schedules and obtain further information on the response rate of liposomal pegylated doxorubicin as a single agent in anthracycline nai ve advanced breast cancer. Twenty-six patients had received prior adjuvant chemotherapy (including an anthracycline in 10). Sixteen had received non-anthracycline-based first-line chemotherapy for advanced disease. One hundred and eleven patients were evaluable for toxicity and 106 for response. The delivered dose intensity (DI) was 9.8 mg/m2 (95% CI, 7.2-10.4) with 37 (69%) achieving a DI of >90% on ARM A and 11.9 mg/m2 (95% CI, 7.5-12.8) with 37 (65%) achieving a DI of >90% on ARM B. The adverse event profiles of the two schedules were distinctly different. Mucositis was more common with the every 6 weeks regimen (35% CTC grade 3/4 in ARM A, 14% in ARM B) but palmar plantar erythrodysesthesia (PPE) was more frequent with the every 4 weeks regimen (2% CTC grade 3/4 in ARM A, 16% in ARM B). Confirmed objective partial responses by RECIST criteria were seen with both schedules; 15/51 (29%) on ARM A and 17/56 (31%) on ARM B. Liposomal pegylated doxorubicin showed significant activity in advanced breast cancer with a generally favourable side-effect profile. The high frequency of stomatitis seen with 6 weekly treatment makes this the less preferred of the two schedules tested.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Lipossomos/uso terapêutico , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
Prediction of outcome in patients with metastatic breast cancer remains problematical. The present study evaluated the value of an inflammation-based score (Glasgow Prognostic Score, GPS) in patients with metastatic breast cancer. The GPS was constructed as follows: patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a score of 2. Patients in whom only one or none of these biochemical abnormalities was present were allocated a score of 1 or 0, respectively. In total, 96 patients were studied. During follow-up 51 patients died of their cancer. On multivariate analysis of the GPS and treatment received, only the GPS (HR 2.26, 95% CI 1.45-3.52, P<0.001) remained significantly associated with cancer-specific survival. The presence of a systemic inflammatory response (the GPS) appears to be a useful indicator of poor outcome independent of treatment in patients with metastatic breast cancer.
Assuntos
Neoplasias da Mama/patologia , Escala de Resultado de Glasgow , Inflamação/patologia , Metástase Neoplásica/patologia , Neoplasias da Mama/mortalidade , Proteína C-Reativa/análise , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Albumina Sérica , Análise de Sobrevida , Taxa de SobrevidaRESUMO
BACKGROUND: Ibandronate is the first third-generation bisphosphonate to have both oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate in female breast cancer patients with metastatic bone disease, undergoing i.v. chemotherapy. METHODS: A global economic model was adapted to the UK National Health Service (NHS), with primary outcomes of direct healthcare costs and quality-adjusted life years (QALYs). Efficacy, measured as relative risk reduction of skeletal-related events (SREs), was obtained from clinical trials. Resource use data for i.v. bisphosphonates and the cost of managing SREs were obtained from published studies. Hospital management and SRE treatment costs were taken from unit cost databases. Monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with/without an SRE to adjust survival for quality of life. Model design and inputs were validated through expert UK clinician review. RESULTS: Total cost, including drug acquisition, was pound 386 less per patient with oral ibandronate vs. i.v. zoledronic acid and pound 224 less vs. i.v. generic pamidronate. Oral ibandronate gained 0.019 and 0.02 QALYs vs. i.v. zoledronic acid and i.v. pamidronate, respectively, making it the economically dominant option. At a threshold of pound 30,000 per QALY, oral ibandronate was cost-effective vs. zoledronic acid in 85% of simulations and vs. pamidronate in 79%. CONCLUSIONS: Oral ibandronate is a cost-effective treatment for metastatic bone disease from breast cancer due to reduced SREs, bone pain, and cost savings from avoidance of resource use commonly associated with bisphosphonate infusions.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Análise Custo-Benefício , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Metástase Neoplásica , Administração Oral , Neoplasias Ósseas/secundário , Ensaios Clínicos Fase III como Assunto , Estudos de Coortes , Difosfonatos/economia , Feminino , Humanos , Ácido Ibandrônico , Imidazóis/economia , Infusões Intravenosas , Pamidronato , Qualidade de Vida , Medicina Estatal , Reino Unido , Ácido ZoledrônicoRESUMO
Menopausal symptoms are a major survivorship issue for patients treated for breast cancer. There are increasing concerns over the use of hormone replacement therapy (HRT) in this setting and a growing consumer interest in "natural" therapies. It had been suggested that soy phyto-oestrogens might be beneficial in the treatment of menopausal symptoms. Seventy-two patients with a histologically confirmed pre-existing diagnosis of breast cancer who were having menopausal symptoms were randomised between 12 weeks of treatment with soy capsules or placebo. Quality of life and menopausal symptom scores were assessed at baseline, 4, 8 and 12 weeks. There was no statistical difference in menopausal symptom scores or quality of life between the two arms of the study.
Assuntos
Neoplasias da Mama , Isoflavonas/uso terapêutico , Menopausa/efeitos dos fármacos , Fitoestrógenos/uso terapêutico , Proteínas de Soja/uso terapêutico , Adulto , Idoso , Cápsulas , Método Duplo-Cego , Feminino , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Medicamentos sem Prescrição , Qualidade de VidaRESUMO
Idoxifene is a novel selective oestrogen receptor modulator (SERM) which had greater binding affinity for the oestrogen receptor (ER) and reduced agonist activity compared with tamoxifen in preclinical studies. In a randomized phase II trial in 56 postmenopausal patients with progressive locally advanced/metastatic breast cancer we assessed whether idoxifene showed evidence of activity compared with an increased 40 mg/day dose of tamoxifen in patients who had previously demonstrated resistance to the standard 20 mg/day dose of tamoxifen. Of 47 patients eligible for response (25 idoxifene, 22 tamoxifen), two partial responses and two disease stabilizations (SD) for >6 months were seen with idoxifene (overall clinical benefit rate 16%, 95% CI 4.5-36.1%). The median duration of clinical benefit was 9.8 months. In contrast, no objective responses were seen with the increased 40 mg/day dose of tamoxifen, although two patients had SD for 7 and 14 months (clinical benefit rate 9%, 95% CI 1.1-29.2%). Idoxifene was well tolerated and the reported possible drug-related toxicities were similar in frequency to those with tamoxifen (hot flushes 13% vs 15%, mild nausea 20% vs 15%). Endocrine and lipid analysis in both groups showed a similar significant fall in serum follicle-stimulating hormone and luteinizing hormone after 4 weeks, together with a significant rise in sex hormone binding globulin levels and 11% reduction in serum cholesterol levels. In conclusion, while idoxifene was associated with only modest evidence of clinical activity in patients with tamoxifen-resistant breast cancer, its toxicity profile and effects on endocrine/lipid parameters were similar to those of tamoxifen.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/análogos & derivados , Tamoxifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/farmacocinética , Disponibilidade Biológica , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Método Duplo-Cego , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Receptores de Superfície Celular/metabolismo , Receptores de Estrogênio/metabolismo , Tamoxifeno/efeitos adversos , Tamoxifeno/farmacocinética , Resultado do Tratamento , Reino UnidoRESUMO
Cardiac damage is recognized to be a potentially serious side effect of breast cancer radiotherapy, the risk of which may be reduced by the choice of appropriate radiotherapy technique. We have previously described variation in physical dose to the heart dependent upon radiotherapy technique. In this paper we report the calculated improvement in normal tissue complication probability (NTCP) (for cardiac damage) achievable by these methods. Cardiac doses were calculated from dose-volume histograms (DVHs) using a "Helax" planning system for 11 patients with left-sided tumours and 5 patients with right-sided tumours. The DVH reduction algorithm of Lyman and Wolbarst [1989] was applied to each DVH to produce a value for the NTCP. For left-sided tumours, mean NTCP with the standard technique was 7.4 +/- 5.6% (range 0.6-17%) and for the optimum technique mean NTCP was 0.3 +/- 0.6% (range 0-2%) (p < 0.003 for the difference between the two techniques): a predicted reduction in late cardiac complications of 23-fold, which is not clearly evident from viewing the DVH raw data.