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Abstract: The incidence rate of prostate cancer (PCa) in many Western countries is high, contributing greatly to the cancer disease bur-den. In most cases, patients progress to metastatic disease defined as castration-resistant prostate cancer after androgen deprivation (mCRPC) following primary treatment where the majority of patients receive first-line new-generation oral hormonal therapies (HT) such as Abiraterone Acetate (AA) and Enzalutamide (ENZ). Despite the importance of correct intake of these drugs, adherence in patients with mCRPC is still poorly investigated and managed with measures not specific to this population. A self-report questionnaire was developed and validated with women with breast cancer treated with oral HT (A-BET). Therefore, this study aims to test the psychometric properties of this instrument on patients with mCRPC treated with AA or ENZ. A prospective observational validation study. The questionnaire was completed by all participants and again after 7/10 days by a randomized subsample to assess stability. Sixty-six patients completed the study (mean age of 72.8 years) and 31 completed the re-test (mean age of 72.7 years). Content validity reported excellent results. Cronbach's alpha of each item showed a strong correlation. Validation of an instrument to measure adherence to HT in patients with mCRPC can be a valuable tool for health professionals involved in patient care. In addition, having a population-specific validated instrument allows to make comparisons between results from different observations.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Femenino , Anciano , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/inducido químicamente , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del Tratamiento , Antagonistas de Andrógenos/uso terapéutico , Psicometría , Estudios Retrospectivos , Acetato de Abiraterona/efectos adversos , Encuestas y Cuestionarios , Hormonas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Purpose: To develop an Italian tool that measures the therapy adherence of women with breast cancer undergoing treatment with oral endocrine therapy. Methods: A two-phase study was conducted, which followed the guidelines of the European Statistical System for the development and validation of a questionnaire. In the first phase, the questionnaire was developed; in the second phase, a preliminary validation was carried out on patients with breast cancer undergoing treatment with oral hormonal therapies. Results: In its final version, the questionnaire presents 6 main items which aim to investigate the level of adherence, the degree of awareness of the nature of the drug taken and the reasons that may influence non-adherence. 82 patients were recruited in the validation study, with an average age of 56.4 years, while for the re-test 40 were selected with an average age of 57.3 years. Content validity reported excellent results. Cronbach's alpha of each item showed a strong degree of correlation. Conclusions: The creation of a tool for measuring adherence to endocrine therapy in breast cancer patients can be a valuable support for healthcare professionals involved in their care. Future studies should be aimed at using A-BET (Adherence - Breast Endocrine Therapy) on larger cohorts of patients in order to verify its validity / reliability more accurately and to be able to generalize the results.
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Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Personal de Salud , Humanos , Persona de Mediana Edad , Psicometría/métodos , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Although the development of bone metastasis is a major detrimental event in prostate cancer, the molecular mechanisms responsible for bone homing and destruction remain largely unknown. Here we show that loss of miR-15 and miR-16 in cooperation with increased miR-21 expression promote prostate cancer spreading and bone lesions. This combination of microRNA endows bone-metastatic potential to prostate cancer cells. Concomitant loss of miR-15/miR-16 and gain of miR-21 aberrantly activate TGF-ß and Hedgehog signaling, that mediate local invasion, distant bone marrow colonization and osteolysis by prostate cancer cells. These findings establish a new molecular circuitry for prostate cancer metastasis that was validated in patients' cohorts. Our data indicate a network of biomarkers and druggable pathways to improve patient treatment.
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Biomarcadores de Tumor/biosíntesis , Neoplasias Óseas/genética , MicroARNs/biosíntesis , Neoplasias de la Próstata/genética , Animales , Neoplasias Óseas/patología , Neoplasias Óseas/secundario , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Hedgehog/biosíntesis , Humanos , Masculino , MicroARNs/genética , Invasividad Neoplásica/genética , Neoplasias de la Próstata/patología , Transducción de Señal/genética , Factor de Crecimiento Transformador beta/biosíntesisRESUMEN
The purpose of this study was to estimate in all randomised trials the relative risk of overall response rate (ORR), clinical benefit (CB), time to progression (TTP), overall survival (OS), and toxicity of aromatase inhibitors (AI), compared with tamoxifen (Tam) as first-line endocrine therapy in postmenopausal metastatic breast cancer (PMBC) women. Prospective randomised studies were searched through computerised queries of MEDLINE, EMBASE, and the American Society of Clinical Oncology (ASCO) abstract database. Relative risk, 95% confidence interval, and heterogeneity were derived according to the inverse variance and Mantel-Haenszel method and Q statistics. Six phase III prospective randomised trials including 2787 women were gathered. A significant advantage in ORR (P = 0.042), TTP (P = 0.007), and CB (P = 0.001) in favour of AI over Tam was detected at the fixed effects model. These results were not significant at the random effects model, owing to the significant heterogeneity. On the contrary, no difference was registered for OS (P = 0.743) with no significant heterogeneity. Regarding toxicity, Tam caused more frequently thromboembolic events (P = 0.005) and vaginal bleeding (P = 0.001) compared with AI. Aromatase inhibitors appear to be superior to Tam as first-line endocrine option in PMBC women. Owing to a component of variability between the six studies analysed, the random effects estimates differed from corresponding fixed ones. Investigators should assess heterogeneity of trial results before deriving summary estimates of treatment effect.
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Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Metástasis de la Neoplasia/tratamiento farmacológico , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/uso terapéutico , Femenino , Humanos , Posmenopausia , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de SupervivenciaRESUMEN
Several chemotherapic agents, which are active against breast cancer, penetrate poorly into the central nervous system. Despite its limited brain penetration, 5-fluorouracil has been a component of effective regimens for brain metastases. Capecitabine is a recently developed oral prodrug that is converted into 5-fluorouracil by sequential enzymatic steps. Thymidine phosphorylase (TP) is the final enzyme responsible for Capecitabine activation. Studies have demonstrated that high intratumoral levels of TP and low levels of its catabolite dihydropyrimidine-dehydrogenase are correlated with the capecitabine response. The penetration of Capecitabine across the brain-blood barrier remains unknown; we report the case of and discuss a breast cancer patient who had an interesting response of brain metastases with Capecitabine in monochemotherapy before brain irradiation.
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Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Desoxicitidina/análogos & derivados , Adulto , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/análogos & derivados , Humanos , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE: To observe whether in pretreated metastatic breast cancer patients with HER2-positive disease vinorelbine plus trastuzumab can produce different overall response rate (ORR), time to progression (TTP), and overall survival (OS) from women with HER2-negative tumors treated with vinorelbine alone. METHODS: Between June 2000 and January 2004, 68 consecutive women were enrolled: 33 patients received vinorelbine (V) alone, while 35 patients were given trastuzumab plus vinorelbine (T+V) according to HER2 expression determined by immunohistochemistry. In tumors scored +2, HER2 gene amplification was determined by fluorescence in situ hybridization. RESULTS: In patients treated with V (HER2-negative tumors) the ORR was 27.3%, while in those given T+V (HER2 positive tumors) the ORR was 51.4%. The median duration of response was 8 months for women treated with V and 10 months for those who received T+V. Patients given T+V had a longer TTP (9 months) and OS (27 months) than those receiving V alone (6 months and 22 months respectively). Toxicity was mild in both groups. Concerning cardiotoxicity in T+V group, 7 patients (20%) had left ventricular systolic disfunction. CONCLUSION: Our data suggest that trastuzumab can change the natural history of HER2-positive metastatic breast cancer. In fact, when treated with trastuzumab, women with HER2-positive disease had better prognosis than patients with HER2-negative tumors. Conducting a formal phase III trial comparing vinorelbine alone vs vinorelbine plus trastuzumab in HER2-positive metastatic breast cancer women could be debatable.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Genes erbB-2 , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Trastuzumab , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
Prostate cancer is the cause of more than 1% of all deaths in men. Its incidence is increasing by 2-3% per year. The general prognosis for diagnosed prostate cancer remains poor, with 70% survival at 10 years compared to the general population. About 50% of the cases are diagnosed at a locally advanced stage, and about 30% have bone metastases at the time of diagnosis. Adjuvant systemic treatments (hormones or chemotherapy), which are effective for advanced-stage disease, might have a greater role in early-stage disease. Advanced prostate cancer is an incurable disease. Treatment objective is palliation only. Here, we review the major controversies concerning hormonal therapy, and provide a general approach to management of patients with early-stage and advanced prostate cancer.
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Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Hormona Liberadora de Gonadotropina/agonistas , Humanos , Masculino , Metástasis de la Neoplasia , Neoplasias de la Próstata/patología , Resultado del TratamientoRESUMEN
This study was performed to determine the activity of adding continuous infusion (CI) of 5-fluorouracil (5-FU) to gemcitabine (GEM) vs GEM alone in advanced pancreatic cancer (APC). In all, 94 chemo-naïve patients with APC were randomised to receive GEM alone (arm A: 1000 mg m(-2) per week for 7 weeks followed by a 2 week rest period, then weekly for 3 consecutive weeks out of every 4 weeks) or in combination with CI 5-FU (arm B: CI 5-FU 200 mg m(-2) day(-1) for 6 weeks followed by a 2 week rest period, then for 3 weeks every 4 weeks). Overall response rate (RR) was the primary end point and criteria for decision were planned according to the Simon's optimal two-stage design. The overall RR was 8% (arm A) and 11% (arm B) (95% confidence interval: 0.5-16% and 2-22%), respectively, and stable disease was 29 and 28%. The median duration of RR was 34 weeks (range 25-101 weeks) for GEM and 26 weeks (range 16-46 weeks) for the combination. The median progression-free survival (PFS) was 14 weeks (range 2-65 weeks) and 18 weeks (range 4-51 weeks), respectively. The median overall survival (OS) was 31 weeks (range 1-101 weeks) and 30 weeks (1-101 weeks). Toxicity was mild in both arms. This study does not show promising activity in terms of RR, PFS and OS for the double combination arm in APC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Adulto , Anciano , Desoxicitidina/administración & dosificación , Progresión de la Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Análisis de Supervivencia , GemcitabinaAsunto(s)
Antibióticos Antineoplásicos/efectos adversos , Biomarcadores/sangre , Doxorrubicina/efectos adversos , Corazón/efectos de los fármacos , Infarto del Miocardio/sangre , Infarto del Miocardio/inducido químicamente , Troponina T/sangre , Humanos , Infarto del Miocardio/diagnóstico , PronósticoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Leucemia Mieloide/inducido químicamente , Síndromes Mielodisplásicos/inducido químicamente , Neoplasias Primarias Secundarias/inducido químicamente , Enfermedad Aguda , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Factores de RiesgoAsunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Doxorrubicina/uso terapéutico , Receptor ErbB-2/biosíntesis , Adulto , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Valor Predictivo de las Pruebas , Pronóstico , Resultado del TratamientoAsunto(s)
Difosfonatos/efectos adversos , Síndrome Hemolítico-Urémico/inducido químicamente , Imidazoles/efectos adversos , Púrpura Trombocitopénica/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Difosfonatos/uso terapéutico , Femenino , Humanos , Imidazoles/uso terapéutico , Persona de Mediana Edad , Ácido ZoledrónicoRESUMEN
This retrospective study compared toxicity and activity of vinorelbine according to two schedules with different projected dose intensities in heavily pretreated breast cancer patients. Forty patients were assessable for toxicity and activity in each group; group A received vinorelbine 25 mg/m2 week + lenograstim (150 microg/m2 s.c. on day 3); group B received 25 mg/m2 on days 1 and 8 every 3 weeks. The projected dose intensity was 25 mg/m2/week and 16.6 mg/m2/week, and delivered dose intensity 95.2% and 94.5% in group A and B, respectively. Grade 3-4 afebrile neutropenia was recorded in 25% and 37.5% of patients in A and B, respectively. Overall response rate, 52.5% and 35%; no change, 35% and 40%; progression of disease, 12.5% and 25% in A and B, respectively. Median duration of the response was 10 months for group A and 7 months for B. Median time to progression: 9.0 months and 4.0 months for A and B, respectively. At a median follow-up of 45 months for group A and 19 months for group B, median overall survival was 19 months and 16, respectively. In conclusion the results of the study showed that dose intensity of vinorelbine could have an improvement in terms of time to progression in pretreated advanced breast cancer.
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Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Vinblastina/análogos & derivados , Vinblastina/uso terapéutico , Adyuvantes Inmunológicos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Lenograstim , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Estudios Retrospectivos , Terapia Recuperativa , Factores de Tiempo , VinorelbinaRESUMEN
Since epidermal growth factor receptor (EGFR) is involved in tumor proliferation and angiogenesis, and in the mechanisms of resistance to chemo- and hormono-therapy, it represents a unique promising target for anticancer treatment. Gefinitib (Iressa, ZD1839), an inhibitor of the EGFR tyrosine kinase activity able to bind the intracellular domain of the receptor, is at present in clinical development. In preclinical models Gefitinib induced a dose-dependent response rate in tumor xenografts obtained from different human cancer cells lines. The expression of EGFR in the prior tumor did not appear to be a predictive marker for Gefitinib sensitivity. Furthermore, long-term drug use was well tolerated in mice without inducing resistance. However, tumors started to grow again after treatment interruption. Laboratory findings and in vivo data have prompted the evaluation of Gefitinib administered as a single oral daily dose alone or in combination with conventional anticancer treatment.
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Antineoplásicos/uso terapéutico , Quinazolinas/uso terapéutico , Animales , Antineoplásicos/farmacocinética , Línea Celular Tumoral/efectos de los fármacos , Ensayos Clínicos como Asunto , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/uso terapéutico , Factor de Crecimiento Epidérmico , Receptores ErbB/antagonistas & inhibidores , Gefitinib , Humanos , Ratones , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Quinazolinas/farmacocinética , Trasplante HeterólogoRESUMEN
BACKGROUND: The aim of this study was to characterize the factors associated with chemotherapy-induced amenorrhea (CIA) and to examine whether the phase of the menstrual cycle at chemotherapy start could affect the rate of CIA in premenopausal women with early breast cancer. METHODS: CIA was defined as the cessation of menses for at least 3 months during or after chemotherapy. Menstrual phase was defined as days 1-6, follicular phase as days 7-14, luteal phase as days 15-20 and premenstrual phase as days 21-28. Univariate and multivariate predictors of CIA were examined. RESULTS: Among 111 premenopausal women, univariate analysis showed a higher incidence of CIA in patients treated in the follicular phase rather than in other menstrual cycle phases (67.6% compared with 45.5%; P=0.03). The rate of CIA increased with age: 65.2% and 45.8% in patients aged >42 and =42 years, respectively (P=0.05). Upon multivariate analysis these differences remained statistically significant and duration of chemotherapy of more than six cycles correlated significantly with the incidence of CIA (P=0.03). CONCLUSIONS: The major implication of this analysis is that the timing of treatment within the menstrual cycle may potentially modulate the onset of CIA. This work and its future confirmation using prospective randomized trials would be useful in predicting the likelihood of CIA and in counseling breast cancer patients, especially those with a good prognosis who benefit less from chemical castration.