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BACKGROUND: Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. METHODS: Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. RESULTS: Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0-1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. CONCLUSIONS: BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients. TRIAL REGISTRATION: NCT03847220. Retrospectively registered on clinicaltrials.gov (February the 20th 2019).
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OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.
Assuntos
Aconselhamento Genético/psicologia , Predisposição Genética para Doença/psicologia , Testes Genéticos/métodos , Neoplasias/psicologia , Adulto , Ansiedade/psicologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/prevenção & controle , EspanhaRESUMO
We have previously demonstrated that male rats exposed to stress during the last week of gestation present age-specific impairments of brain development. Since the organization of the fetal developing brain is subject to androgen exposure and prenatal stress was reported to disrupt perinatal testosterone surges, the aim of this research was to explore whether abnormal androgen concentrations during late gestation affects the morphology of the prefrontal cortex (PFC), hippocampus (HPC) and ventral tegmental area (VTA), three major areas that were shown to be affected by prenatal stress in our previous studies. We administered 10-mg/kg/day of the androgen receptor antagonist flutamide (4'nitro-3'-trifluoromethylsobutyranilide) or vehicle injections to pregnant rats from days 15-21 of gestation. The antiandrogenic effects of flutamide were confirmed by the analysis of androgen-dependent developmental markers: flutamide-exposed rats showed reduced anogenital distance, delay in the completion of testis descent, hypospadias, cryptorchidism and atrophied seminal vesicles. Brain morphological studies revealed that prenatal flutamide decreased the number of MAP2 (a microtubule-associated protein type 2, present almost exclusively in dendrites) immunoreactive neuronal processes in all evaluated brain areas, both in prepubertal and adult offspring, suggesting that prenatal androgen disruption induces long-term reductions of the dendritic arborization of several brain structures, affecting the normal connectivity between areas. Moreover, the number of tyrosine hydroxylase (TH)-immunopositive neurons in the VTA of prepubertal offspring was reduced in flutamide rats but reach normal values at adulthood. Our results demonstrate that the effects of prenatal flutamide on the offspring brain morphology resemble several prenatal stress effects suggesting that the mechanism of action of prenatal stress might be related to the impairment of the organizational role of androgens on brain development.
Assuntos
Androgênios/fisiologia , Encéfalo/crescimento & desenvolvimento , Estresse Fisiológico , Antagonistas de Androgênios/administração & dosagem , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Feminino , Flutamida/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/crescimento & desenvolvimento , Córtex Pré-Frontal/metabolismo , Gravidez , Ratos , Ratos Wistar , Testosterona/sangue , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/crescimento & desenvolvimento , Área Tegmentar Ventral/metabolismoRESUMO
BACKGROUND: Src is a non-receptor tyrosine kinase involved in signalling and crosstalk between growth-promoting pathways. We aim to investigate the relationship of active Src in response to trastuzumab of HER2-positive breast carcinomas. METHODS: We selected 278 HER2-positive breast cancer patients with (n=154) and without (n=124) trastuzumab treatment. We performed immunohistochemistry on paraffin-embedded tissue microarrays of active Src and several proteins involved in the PI3K/Akt/mTOR pathway, PIK3CA mutational analysis and in vitro studies (SKBR3 and BT474 cancer cells). The results were correlated with clinicopathological factors and patients' outcome. RESULTS: Increased pSrc-Y416 was demonstrated in trastuzumab-resistant cells and in 37.8% of tumours that correlated positively with tumour size, necrosis, mitosis, metastasis to the central nervous system, p53 overexpression and MAPK activation but inversely with EGFR and p27. Univariate analyses showed an association of increased active Src with shorter survival in patients at early stage with HER2/hormone receptor-negative tumours treated with trastuzumab. CONCLUSIONS: Src activation participates in trastuzumab mechanisms of resistance and indicates poor prognosis, mainly in HER2/hormone receptor-negative breast cancer. Therefore, blocking this axis may be beneficial in those patients.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/enzimologia , Neoplasias do Sistema Nervoso Central/enzimologia , Receptor ErbB-2/metabolismo , Quinases da Família src/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/secundário , Quimioterapia Adjuvante , Classe I de Fosfatidilinositol 3-Quinases , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Fosfatidilinositol 3-Quinases/genética , Transdução de Sinais , Trastuzumab , Quinases da Família src/antagonistas & inibidoresRESUMO
BACKGROUND: Trastuzumab resistance hampers its well-known efficacy to control HER2-positive breast cancer. The involvement of PI3K/Akt pathway in this mechanism is still not definitively confirmed. METHODS: We selected 155 patients treated with trastuzumab after development of metastasis or as adjuvant/neoadjuvant therapy. We performed immunohistochemistry for HER2, ER/PR, epidermal growth factor 1-receptor (EGFR), α-insulin-like growth factor 1-receptor (IGF1R), phosphatase and tensin homologue (PTEN), p110α, pAkt, pBad, pmTOR, pMAPK, MUC1, Ki67, p53 and p27; mutational analysis of PIK3CA and PTEN, and PTEN promoter hypermethylation. RESULTS: We found 46% ER/PR-positive tumours, overexpression of EGFR (15%), α-IGF1R (25%), p110α (19%), pAkt (28%), pBad (22%), pmTOR (23%), pMAPK (24%), MUC1 (80%), PTEN loss (20%), and PTEN promoter hypermethylation (20%). PIK3CA and PTEN mutations were detected in 17% and 26% tumours, respectively. Patients receiving adjuvant trastuzumab with α-IGF1R or pBad overexpressing tumours presented shorter progression-free survival (PFS) (all P≤0.043). Also, p110α and mTOR overexpression, liver and brain relapses implied poor overall survival (OS) (all P≤0.041). In patients with metastatic disease, decreased PFS correlated with p110α expression (P=0.024), whereas for OS were the presence of vascular invasion and EGFR expression (P≤0.019; Cox analysis). CONCLUSION: Our results support that trastuzumab resistance mechanisms are related with deregulation of PTEN/PI3K/Akt/mTOR pathway, and/or EGFR and IGF1R overexpression in a subset of HER2-positive breast carcinomas.
Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosfatidilinositol 3-Quinases/genética , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Análise de Sobrevida , TrastuzumabRESUMO
The following manuscript summarises the content of the Breast Symposium that was held in May 2008 in Barcelona in which four controversies regarding the management of breast cancer were discussed. The design of the symposium included two speakers per controversy, one in favour and one diverging, and the audience had to vote before and after the presentations to assess changes in the participants' views. The four controversies included: (1) the role of non-conventional predictive factors in selecting treatment for breast cancer; (2) the role of surgery in disseminated disease; (3) are taxanes indicated in the adjuvant treatment of patients with lymph-node-negative disease?; (4) is treatment with tamoxifen (TAM) always required after surgery in patients with ductal carcinoma in situ (DCIS)? The symposium concluded with the presentation titled: 'Features of a well designed clinical trial in the adjuvant treatment of breast cancer'.
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Neoplasias da Mama/terapia , Antineoplásicos/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Humanos , MastectomiaRESUMO
The following manuscript summarises the content of the Breast Symposium that was held in May 2008 in Barcelona in which four controversies regarding the management of breast cancer were discussed. The design of the symposium included two speakers per controversy, one in favour and one diverging, and the audience had to vote before and after the presentations to assess changes in the participants' views. The four controversies included: (1) the role of non-conventional predictive factors in selecting treatment for breast cancer; (2) the role of surgery in disseminated disease; (3) are taxanes indicated in the adjuvant treatment of patients with lymph-node-negative disease?; (4) is treatment with tamoxifen (TAM) always required after surgery in patients with ductal carcinoma in situ (DCIS)? The symposium concluded with the presentation titled: 'Features of a well designed clinical trial in the adjuvant treatment of breast cancer' (AU)
No disponible
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Humanos , Feminino , Neoplasias da Mama/terapia , Ensaios Clínicos como Assunto , Antineoplásicos/uso terapêutico , Terapia Combinada , Mastectomia/métodos , Mastectomia/tendências , MastectomiaRESUMO
INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS: Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/biossíntese , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , DNA Topoisomerases Tipo II/biossíntese , Proteínas de Ligação a DNA/biossíntese , Docetaxel , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose , Proteínas Associadas aos Microtúbulos/biossíntese , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Nuclear de Célula em Proliferação/biossíntese , Survivina , Taxoides/administração & dosagem , Taxoides/efeitos adversosRESUMO
INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS: Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer (AU)
No disponible
Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , DNA Topoisomerases Tipo II/biossíntese , Antígenos de Neoplasias/biossíntese , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Imuno-Histoquímica , Proteínas Associadas aos Microtúbulos/biossínteseRESUMO
Doxorubicin and gemcitabine are active as single agents in breast cancer, have different mechanisms of action, and mainly have non-overlapping side effects. Dose-dependent doxorubicin-related cardiac toxicity is the principal limitation in the metastatic setting. This open, multicenter, single-arm phase I/II study assessed the safety and activity of gemcitabine in combination with non-pegylated liposomal doxorubicin (Myocet), a more cardiac-friendly anthracycline, in the first-line treatment of patients with advanced breast cancer. We aimed to determine the optimal recommended dose (RD) of gemcitabine combined with Myocet in a population, with performance status >or=2 and LVEF >or=50%. A formal phase II study was performed afterwards. A total of 53 patients were recruited. Gemcitabine 900 mg/m(2) intravenously day 1 and 8 combined with Myocet 55 mg/m(2) intravenously day 1, every 21 days, was the final RD. The principal toxicity observed was hematological, and 48% of patients developed grade 3-4 neutropenia. Other toxicities were mild and infrequent, including nausea and vomiting. There were no symptomatic cardiac events despite the fact that 36% of the patients had received prior treatment with adjuvant anthracyclines. Objective responses were observed in 51.1% of 47 evaluable patients (95% CI: 36-66%), including two complete response. In addition, 14 patients (29.8%) demonstrated stable disease. The combination of Myocet and gemcitabine at the RD is safe and has encouraging clinical activity in patients with advanced breast cancer, without apparent cardiac toxicity in anthracycline-pretreated patients. These data support further development of this combination.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Lipossomos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Resultado do Tratamento , GencitabinaRESUMO
Medical professionals in general, and medical oncologists in particular, have highly stressful practices because they are under constant pressure to have the highest-quality, up-to-date evidence available in order to make the right decision for each individual patient. From a practical point of view, being updated on oncological and other medical specialties may seem an insurmountable task because the number of scientific publications has increased dramatically. The use of systematic reviews of randomised controlled trials or the application of results obtained from high-quality randomised controlled trials are some of the most common ways to address this need. Unfortunately, they do not cover all complex clinical situations that the majority of medical oncologists face in their outpatient consultations. In this review, we report the conclusions achieved in a multiexpert meeting where five important controversies in the treatment of breast cancer were analysed. Five highly experienced medical oncologists were required to defend an affirmative answer and another five were required to defend a negative answer for each of the clinical questions. After that, a one-day meeting was organised to debate each clinical question and to reach a consensus. We report here the content of this multi-expert meeting along with the conclusions drawn.
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Neoplasias da Mama/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Regulação Neoplásica da Expressão Gênica , Genes erbB-2/genética , Humanos , Terapia Neoadjuvante , Ovariectomia , Biópsia de Linfonodo Sentinela , TrastuzumabRESUMO
Medical professionals in general, and medical oncologists in particular, have highly stressful practices because they are under constant pressure to have the highest-quality, up-to-date evidence available in order to make the right decision for each individual patient. From a practical point of view, being updated on oncological and other medical specialties may seem an insurmountable task because the number of scientific publications has increased dramatically. The use of systematic reviews of randomised controlled trials or the application of results obtained from high-quality randomised controlled trials are some of the most common ways to address this need. Unfortunately, they do not cover all complex clinical situations that the majority of medical oncologists face in their outpatient consultations. In this review, we report the conclusions achieved in a multiexpert meeting where five important controversies in the treatment of breast cancer were analysed. Five highly experienced medical oncologists were required to defend an affirmative answer and another five were required to defend a negative answer for each of the clinical questions. After that, a one-day meeting was organised to debate each clinical question and to reach a consensus. We report here the content of this multi-expert meeting along with the conclusions drawn (AU)
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Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Genes erbB-2/genética , Ovariectomia/métodos , Ovariectomia , Biópsia de Linfonodo Sentinela/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante , Regulação Neoplásica da Expressão Gênica , Terapia Neoadjuvante/métodos , Terapia NeoadjuvanteRESUMO
BACKGROUND: The aim of the study was to analyse the toxicity and health related quality of life (HRQoL) of breast cancer patients treated with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) and TAC (docetaxel, doxorubicin, cyclophosphamide) with and without primary prophylactic G-CSF (PPG). PATIENTS AND METHODS: This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients. After the entry of the first 237 patients, the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia. A total of 1047 evaluable patients from 49 centres in Spain, two in Poland and four in Germany were included in the trial. Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 questionnaires were compared in the three groups (FAC, TAC pre-amendment and TAC post-amendment). RESULTS: The addition of PPG to TAC significantly reduced the incidence of neutropenic fever, grade 2-4 anaemia, asthenia, anorexia, nail disorders, stomatitis, myalgia and dysgeusia. Patient QoL decreased during chemotherapy, more with TAC than FAC, but returned to baseline values afterwards. The addition of PPG to TAC significantly reduced the percentage of patients with clinically relevant Global Health Status deterioration (10 or more points over baseline value) at the end of chemotherapy (64% versus 46%, P<0.03). CONCLUSIONS: The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects. The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG, particularly in the final part of chemotherapy treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neutropenia/prevenção & controle , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Docetaxel , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/prevenção & controle , Humanos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Qualidade de Vida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Taxoides/uso terapêuticoRESUMO
BACKGROUND: The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. PATIENTS AND METHODS: Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). RESULTS: Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. CONCLUSIONS: Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.
Assuntos
Carboplatina/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Cuidados Paliativos , Adulto , Idoso , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Intervalos de Confiança , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Ovariectomia/métodos , Paclitaxel/efeitos adversos , Probabilidade , Prognóstico , Qualidade de Vida , Medição de Risco , Espanha , Análise de Sobrevida , Resultado do TratamentoRESUMO
3% of human cancers are renal cell carcinomas (RCC). The most common chromosome abnormality found in this tumor is loss of heterozygosity (LOH) on the short arm of chromosome 3, which suggests that there must be one or more tumor suppressor genes between 3p14 and 3p21 near the VHL gene which play a relevant role in renal cancer development. DNA from normal and tumor tissue from 40 patients at various stages of RCC was analyzed for LOH at three microsatellites mapped to 3p (3p14.1-14.3; 3p21.2-21.3 and 3p25) by polymerase chain reaction). 42.5% of the tumors studied showed LOH on at least one locus. 30% showed LOH on only one locus; 5% on two loci and 7.5% on the three loci tested. LOH occurred only on nonpapillary tumors (p = 0.03). Interestingly, all the tumors with LOH on 3p21 were >/=25 mm (p = 0.04; relative risk 1.76, confidence interval: 1.3-2.3).
Assuntos
Cromossomos Humanos Par 3 , Neoplasias Renais/genética , Perda de Heterozigosidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-IdadeRESUMO
The expression of p53 protein was examined in a series of 111 colorectal cancer adenocarcinomas with a long follow-up. A quantitative luminometric immunoassay (LIA) was used for the measurement of wild-type and mutant p53 protein in extracts from colorectal tumour cytosols, p53 being detected in 42% of the samples (range 0.0-52 ng (mg-1)). Using an arbitrary cut-off value of 2.7 ng mg(-1), 25% of the tumours were classified as manifesting high p53 levels. There was no association of p53 expression with patient age, sex, serum preoperative carcinoembryonic antigen (CEA) levels, tumour site and size, nodal status or TNM stage. Significant and independent correlation was found to exist between high p53 levels and prolonged disease-free survival (P = 0.05) at a median follow-up of 60 months. This survival advantage was most apparent among stage III cancer patients. The results from this study would suggest that expression of high p53 levels appear to be useful in selecting a group of colorectal cancer patients with a better prognosis.
Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/biossíntese , Neoplasias Colorretais/química , Proteína Supressora de Tumor p53/biossíntese , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Proteína Supressora de Tumor p53/metabolismoRESUMO
PURPOSE: This study was undertaken to assess the antitumor activity and tolerance of chronic oral etoposide (50 mg/m2/d for 21 days every 4 weeks) in metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-three consecutive metastatic breast cancer patients with at least one site of measurable disease entered the study. All patients had received prior chemotherapy (adjuvant, three patients; adjuvant plus chemotherapy for metastases, 21; chemotherapy for metastases, 19). Twenty-two and 21 patients had also received prior hormonal and radiation therapy, respectively. RESULTS: Thirty-five percent of patients (15 of 43; 95% confidence interval, 21% to 51%) had objective responses, according to an intention-to-treat analysis. Responses were seen in lymph nodes (six of 14), skin and soft tissues (eight of 16), lung (six of 14), lytic lesions of the bone (two of six), liver (four of 23), and peritoneum (one of one). The median duration of response was 7 months (range, 3+ to 12). The main toxic side effects were leukopenia (overall, 65% of patients; World Health Organization [WHO] grade 4, 21%), thrombocytopenia (21%; WHO grade 4, 5%) and anemia (51%; WHO grade 4, 5%). Nine patients (21%) required a 25% dose reduction because of myelosuppression, and one patient abandoned treatment because of gastrointestinal toxicity and severe asthenia. Ninety-one percent of patients developed alopecia, 39.5% had mucositis (WHO grade 3, 9.5%) and 60.5% had some degree of emesis (11.5% nausea, 46.5% transient vomiting, 2.5% intractable vomiting). No toxic deaths occurred. CONCLUSION: Chronic oral etoposide appears to be an active and well-tolerated regimen in MBC patients previously exposed to chemotherapy. This schedule of etoposide administration warrants further studies, alone or in combination, in MBC.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Etoposídeo/uso terapêutico , Administração Oral , Adulto , Idoso , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
Twenty-seven women with metastatic breast cancer (at least one site of measurable disease) entered a phase II study of chronic oral etoposide (50 mg/m2/day x 21 days, given every 4 weeks). To date, 23 patients are evaluable for response and toxicity. All patients had received prior chemotherapy (adjuvant therapy, one patient; adjuvant plus chemotherapy for metastases, six patients; chemotherapy for metastases, 16 patients). Thirteen patients had previously received anthracyclines, and 10 had also received prior hormonal therapy. Of the 23 evaluable patients, one obtained a complete response and six achieved partial responses (objective response rate 30.4%, 95% confidence interval, 13 to 53%). Responses were seen in lymph nodes (three of eight sites), skin and soft tissue (five of seven), lung (two of six), lytic lesions of the bone (one of three), and liver (1 of 12). The median duration of responses was 6 months (range, 1+ to 8). The main toxic side-effects were leukopenia (74% of patients), thrombocytopenia (22%), and anemia (69.5%). Myelosuppression in four patients (17%) necessitated a 25% dose reduction. Other toxicities included alopecia (83%), mucositis (52%), and emesis (35%). Chronic oral etoposide appears to be an active regimen in metastatic breast cancer patients previously exposed to chemotherapy.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Etoposídeo/uso terapêutico , Administração Oral , Adulto , Idoso , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
PURPOSE: The study was undertaken to assess the antitumor activity of carboplatin 400 mg/m2 intravenously every 4 weeks in metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-four MBC patients without any prior exposure to chemotherapy entered the study. All patients had measurable disease in at least one site and were assessable for response and toxicity. RESULTS: Of 34 assessable patients, 12 obtained a complete (one) or partial (11) response to carboplatin, resulting in an overall response rate of 35% (95% confidence interval, 19.8% to 53.5%). The median duration of response was 8 months (range, 2+ to 12 months). Responses were seen in lymph nodes (four of six), lung (five of nine), skin and soft tissues (four of nine), breast (two of eight), and liver (three of 11), but not in measurable lytic lesions of the bone. Toxicity was mild, mainly consisting of emesis (81% of the patients; 66% of the courses), leukopenia of World Health Organization (WHO) grade 1 to 2 (47% of the patients; 18% of the courses), and thrombocytopenia (12% of the patients; 3% of the courses). There were no cases of life-threatening toxicity, although one patient developed grade 4 thrombocytopenia without bleeding. Of 22 patients who did not respond to carboplatin, 18 received salvage therapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF; 15 patients); cyclophosphamide, methotrexate, and fluorouracil (CMF; one patient); or hormones (two patients). Objective responses to CAF and hormonal therapy were seen in 11 of 15 and two of two patients, respectively. The remaining patient did not respond to CMF salvage chemotherapy. Overall, the response rate to either first-line carboplatin or second-line salvage therapy was 73.5% (25 of 34 patients). After a median follow-up time of 22 months, the median survival was 19 months. CONCLUSIONS: Carboplatin is an active drug in MBC patients without previous exposure to chemotherapy. In our study, the use of an experimental drug as first-line single-agent treatment in MBC did not have a negative influence on patient survival, as the majority of the carboplatin nonresponding patients could be salvaged with a conventional therapeutic regimen.