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BACKGROUND: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. METHODS: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2-9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2-3 arm A vs B, 19% and 38%, respectively). CONCLUSION: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease. TRIAL REGISTRATION: EudraCT, 2012-002707-18 . Registered on June 4, 2012. NIH ClinicalTrials.gov, NCT02783222 . Retrospectively registered on May 26, 2016.
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Albúminas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/uso terapéutico , Factores de Edad , Anciano , Anciano de 80 o más Años , Albúminas/efectos adversos , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/patología , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Invasividad Neoplásica , Estadificación de Neoplasias , Paclitaxel/efectos adversos , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Metronomic oral vinorelbine could be a safe option for elderly patients with advanced non small cell lung cancer (NSCLC). Metronomic administration of chemotherapy leads to a cytostatic action shifting treatment target from cancer cell to tumor angiogenesis. METHODS: 43 chemotherapy naive elderly (≥ 70 yrs) PS 0-2 patients with stage IIIB-IV NSCLC were prospectively recruited. Median age was 80 yrs (M/F 36/7) with predominantly squamous histology. PS distribution was 0-1(16)/2(27) with a median of 3 serious co-morbid illnesses. Study treatment consisted of oral vinorelbine 50mg three times weekly (Monday-Wednesday-Friday) continuously until disease progression, unacceptable toxicity or patient refusal. Primary endpoints were overall response rate (ORR), clinical benefit (CB--disease response plus disease stabilization >12 weeks) and safety. Health-related QoL (HRQoL) was also assessed with FACT-L V4 scoring questionnaire. We conducted an exploratory time-course analysis of VEGF and thrombospondin-1 (TSP1) serum levels in a subgroup of patients. RESULTS: Patients received a median of 5 (range 1-21) cycles with a total of 272 cycles delivered. ORR was 18.6% with 7 partial and 1 complete responses; 17/43 experienced stable disease lasting more than 12 weeks leading to an overall CB of 58.1%. Median time to progression was 5 (range 2-21) and median overall survival 9 (range 3-29) months. Treatment was well tolerated with rare serious toxicity. Regardless of severity main toxicities observed were anemia in 44%, fatigue in 32.4%, and diarrhoea 10.5%. FACT-L v4 scores did not significantly vary during treatment. Baseline VEGF levels were lower and showed a rapid increase during treatment in non-responders pts only while TSP1 levels did not change. CONCLUSIONS: Metronomic oral vinorelbine is safe in elderly patients with advanced NSCLC with an interesting activity mainly consisting in long-term disease stabilization coupled with an optimal patient compliance (Eudra-CT 2010-018762-23, AIFA OSS on 26 February 2010).
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Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Vinblastina/análogos & derivados , Administración Metronómica , Administración Oral , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/sangre , Vinblastina/administración & dosificación , VinorelbinaRESUMEN
BACKGROUND: Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET). PATIENTS AND METHODS: The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials. RESULTS: Between October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases. CONCLUSIONS: AI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.
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BACKGROUND/AIM: There is controversy around the use of high-sensitive troponin T (hs-TnT) as an early biomarker of cardiac toxicity in patients with breast cancer on trastuzumab (T). PATIENTS AND METHODS: Patients receiving adjuvant or neo-adjuvant T for early HER2-positive breast cancer were prospectively included. Transthoracic echocardiograms and matched hs-TnT before T and at 3, 6, and 9 months were performed on all patients. Congestive heart failure, cardiac death, a decline in left ventricular ejection fraction (LVEF) of more than 10% from baseline even if it is still within the normal range, or a drop in LVEF below 55% were all considered signs of cardiac toxicity. RESULTS: In total, 24 patients (median age: 57; range=39-79 years) were enrolled. Anthracyclines were administered to all patients but three as part of neo/adjuvant treatment before T. Cardiovascular toxicity was observed in 3 out of 24 (12.5%) patients: two non-symptomatic LVEF declines (8.3%) and one heart failure episode (4.2%). In the entire population, the mean baseline hs-TnT level was 10.1±8.8 pg/ml, and after 3, 6, and 12 months, no appreciable change was observed. Patients with cardiac toxicity had mean hs-TnT levels higher than those without (18.3±12.3 vs. 8.2±7.2 pg/ml; p=0.049). A definite trend was evident in the chi-square test (chi2=3.52; p=0.06). CONCLUSION: In anthracycline-exposed patients with early breast cancer, hs-TnT may be able to identify those at risk of developing cardiac toxicity during neo/adjuvant T treatment.
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Neoplasias de la Mama , Insuficiencia Cardíaca , Humanos , Persona de Mediana Edad , Femenino , Trastuzumab/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad/etiología , Cardiotoxicidad/diagnóstico , Troponina , Volumen Sistólico , Función Ventricular Izquierda , Insuficiencia Cardíaca/diagnóstico , Antraciclinas/efectos adversos , Troponina T , Receptor ErbB-2RESUMEN
To investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8, HIF-1α, EPAS-1, and TSP-1 SNPs and their role on progression-free survival (PFS) in metastatic breast cancer (MBC) patients treated with bevacizumab plus first-line paclitaxel or with paclitaxel alone. Analyses were performed on germline DNA, and SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction (MDR) methodology was applied to investigate the interaction between SNPs. The present study was an explorative, ambidirectional cohort study: 307 patients from 11 Oncology Units were evaluated retrospectively from 2009 to 2016, then followed prospectively (NCT01935102). Two hundred and fifteen patients were treated with paclitaxel and bevacizumab, whereas 92 patients with paclitaxel alone. In the bevacizumab plus paclitaxel group, the MDR software provided two pharmacogenetic interaction profiles consisting of the combination between specific VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes. Median PFS for favorable genetic profile was 16.8 vs. the 10.6 months of unfavorable genetic profile (p = 0.0011). Cox proportional hazards model showed an adjusted hazard ratio of 0.64 (95% CI, 0.5-0.9; p = 0.004). Median OS for the favorable genetic profile was 39.6 vs. 28 months of unfavorable genetic profile (p = 0.0103). Cox proportional hazards model revealed an adjusted hazard ratio of 0.71 (95% CI, 0.5-1.01; p = 0.058). In the 92 patients treated with paclitaxel alone, the results showed no effect of the favorable genetic profile, as compared to the unfavorable genetic profile, either on the PFS (p = 0.509) and on the OS (p = 0.732). The pharmacogenetic statistical interaction between VEGF-A rs833061 and VEGFR-2 rs1870377 genotypes may identify a population of bevacizumab-treated patients with a better PFS.
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BACKGROUND/AIM: Cardiovascular risk factors (CVRFs) predict cardiotoxicity in cancer patients but their role in late cardiac toxicity is less clear. PATIENTS AND METHODS: This was a retrospective analysis of patients treated with anthracyclines (A) and/or trastuzumab (T) and a correlation with early (≤5 years) or late (>5 years) cardiac toxicity, and baseline CVRFs and CVRFs at toxicity time. RESULTS: A total of 610 patients were included, 422 with (Group A) and 188 without (Group B) baseline CVRFs. In group A toxicity incidence was 4.7% with all events during treatment or immediately after [mean onset time 0.7 years (range=0.2-1.6)]. Events rate was 3.2% in group B with all events after five years [mean time onset 6.9 years (range=5.2-7.5)]. All group B patients who developed late cardiac toxicity presented with CVRFs at the time of toxicity not reported before. CONCLUSION: CVRFs could predict late cardiac toxicity and their control should be part of the survivorship program.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Cardiotoxicidad/etiología , Cardiopatías/inducido químicamente , Adulto , Anciano , Antraciclinas/administración & dosificación , Antraciclinas/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trastuzumab/administración & dosificación , Trastuzumab/efectos adversosRESUMEN
BACKGROUND: We aimed to explore the use of platinum plus bevacizumab in a real world NSCLC population. PATIENTS AND METHODS: We retrospectively collected data from patients affected by NS-NSCLC treated with platinum plus bevacizumab across Tuscany. RESULTS: We evaluated 62 (median age: 63.5 [30-77] years) pts. All but one presented with adenocarcinoma and the majority had ECOG PS of 0/1. 17.7% presented with central lesion, 11.3% with brain metastasis, 38.7% with hypertension and 4.8% with mild haemoptysis. We observed a median time to progression (TTP) of 6.5 [2-37] and a median overall survival (OS) of 10.5 [2-39] months. Overall response rate (ORR) was 59.6% with a disease control rate (DCR) of 80.6%. Safety profile was acceptable. We observed five cardiovascular events and two major bleedings with no toxic deaths. CONCLUSION: Safety and efficacy real world data are consistent with those from clinical trials even in a less selected population.
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Inhibidores de la Angiogénesis/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Bevacizumab/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Italia , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Compuestos de Platino/administración & dosificación , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND/AIM: The optimal therapeutic use of metronomic vinorelbine has not yet been defined. We aimed to assess the safety of metronomic oral vinorelbine in first-line treatment of elderly patients with advanced lung cancer who were unfit for polychemotherapy. Progression-free survival, response rate and overall survival were secondary end-points. PATIENTS AND METHODS: Seventy-six patients received 50 mg of oral vinorelbine three times per week, until disease progression, patient refusal or unacceptable toxicity. Patients were evaluated for response and toxicity after one cycle of chemotherapy. The treatment was considered feasible with a grade 3/4 toxicity rate lower than 20%. RESULTS: Clinical benefit was observed in 50% of patients. Median overall survival was 8.0 months. Grade 1/2 toxicity was observed in 53 patients (69.7%), grade 3 toxicity in eight patients (10.5%). One patient had grade 4 diarrhea. CONCLUSION: Metronomic oral vinorelbine is safe in elderly patients, allowing for long-term disease stabilization with optimal patient compliance.
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Antineoplásicos Fitogénicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Vinblastina/análogos & derivados , Administración Metronómica , Administración Oral , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Italia , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Cumplimiento de la Medicación , Proyectos Piloto , Factores de Tiempo , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , VinorelbinaRESUMEN
The burden of cardiac side effects in oncology patients will dramatically increase in the near future as a result of the widespread use of anticancer agents affecting the cardiovascular system, the general population aging, the heightened attention in the detection of cardiac toxicity and the absolute gain in terms of overall survival. The relationship between cardiologists and oncologists should therefore be closer leading to the definition of cardio-oncology. The increased number of such patients requires the creation of a dedicated patient assistance program in order to guarantee every patient the possibility of an interdisciplinary and multiprofessional approach. A dedicated care pathway needs a reorganization of internal resources to ensure high standards of care. The proposed pathway is actually active at our institution and has been implemented taking into account available facilities and planned work amount. Our patient cardio-oncology program could be adapted with minimal changes to different hospitals.
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Cardiología , Vías Clínicas , Cardiopatías/terapia , Comunicación Interdisciplinaria , Oncología Médica , Neoplasias/terapia , Grupo de Atención al Paciente , Cardiotoxicidad/etiología , Cardiotoxicidad/terapia , Cardiopatías/etiología , Hospitalización , Humanos , Neoplasias/complicaciones , Diseño de SoftwareRESUMEN
AIM: To investigate pharmacogenetic interactions among VEGF-A, VEGFR-2, IL-8, HIF-1α, EPAS-1 and TSP-1 SNPs and their role on progression-free survival in a population of metastatic breast cancer patients treated with bevacizumab in combination with first-line paclitaxel. PATIENTS & METHODS: Analyses were performed on germline DNA obtained from blood samples and SNPs were investigated by real-time polymerase chain reaction technique. The multifactor dimensionality reduction methodology was applied to investigate the interaction between SNPs. RESULTS: One hundred and thirteen patients were enrolled from eight Italian Oncology Units ( clinicaltrial.gov : NCT01935102). The multifactor dimensionality reduction software provided two pharmacogenetic interaction profiles consisting of the combination between specific VEGFR-2 rs11133360 and IL-8 rs4073 genotypes. The median progression-free survival was 14.1 months (95% CI: 11.4-16.8) and 10.2 months (95% CI: 8.8-11.5) for the favorable and the unfavorable genetic profile, respectively (HR: 0.44, 95% CI: 0.29-0.66, p < 0.0001). CONCLUSION: The pharmacogenetic statistical interaction between VEGFR-2 rs11133360 and IL-8 rs4073 genotypes may identify a population of patients with a better outcome.
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Neoplasias de la Mama/genética , Interleucina-8/genética , Farmacogenética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Bevacizumab , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Asociación Genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Polimorfismo de Nucleótido Simple , Trombospondina 1/genética , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
BACKGROUND: The human epidermal growth factor receptor 2 (HER2) and p53 pathways may be involved in chemotherapy sensitivity and/or resistance. We explore the value of HER2 and p53 status to foretell docetaxel sensitivity in advanced breast cancer. METHODS: HER2 and p53 expression was analysed in 36 (median age 55 yrs; range 37-87) metastatic breast cancer patients receiving docetaxel-based first-line chemotherapy. HER2 was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), p53 was tested by IHC. We correlate the expression of study parameters with pathologic parameters, RECIST response and survival. The standard cut-off value of 2 was used to determine HER2 overexpression while p53 mean expression level was used to divide low/high expressors tumors. RESULTS: Median time to progression and overall survival were 9 (range 2-54) and 20 (range 3-101) months. Overall response rate was 41.6%. Nine cases showed HER2 overexpression. HER2 was more frequently overexpressed in less differentiated (p=0.05) and higher stage (p=0.003) disease. Mean FISH-HER2 values were significantly higher in responder than in non-responder pts (8.53±10.21 vs 2.50±4.12, p=0.027). Moreover, HER2 overexpression correlates with treatment response at cross-tabulation analysis (p=0.046). p53 expression was only associated with higher stage disease (p=0.02) but lack of any significant association with HER status or docetaxel response. No significant relation with survival was observed for any parameter. CONCLUSION: Our data seem to indicate that FISH-determined HER2 status but not p53 is associated with docetaxel sensitivity in metastatic breast cancer.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Receptor ErbB-2/biosíntesis , Taxoides/uso terapéutico , Proteína p53 Supresora de Tumor/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/enzimología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/cirugía , Terapia Combinada , Docetaxel , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
INTRODUCTION: sorafenib, a tyrosine-kinase inhibitor, is widely used in the treatment of advanced hepatocellular carcinoma. Drug-related toxicities are generally mild but sorafenib, as other similar agents, may induce elevation of systemic arterial blood pressure levels in relation to an interaction with cardiovascular system probably mediated by HIF pathway. This side effect may be particularly critical for patients with underlying serious heart disease as it can induce acute heart failure, a life-threatening condition, and usually such patients are excluded from active treatment with tyrosine-kinase inhibitors. We report the case of a patient affected by advanced hepatocellular carcinoma and serious impairment of cardiac function treated with sorafenib without any worsening of heart function. To our knowledge this is the first report of this kind in the literature. CASE PRESENTATION: We report the case of a 74-year-old patient affected by advanced multifocal HCV-cirrhosis related hepatocellular carcinoma and severe post-ischemic fall of left-ventricular function with serious risk of cardiac functional impairment. The patient presented with an ECOG performance status of 0. Blood chemistry tests showed a substantial elevation of alpha-fetoprotein values and slight increases of bilirubin, of gamma-GT and of GOT; the absence of encephalopathy and ascites and the normality of coagulation parameters and of albumin led to classify the patient into the functional class Child-Pugh A. The patients was successfully treated with sorafenib at the reduced daily dose of 400 mg for long-time without any worsening of heart function. CONCLUSION: The presented case can offer to oncologists a clinical support to take into consideration when deciding to treat with sorafenib advanced hepatocellular carcinoma patients presenting with serious impairment of cardiac function that are usually excluded from an active treatment.
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BACKGROUND: Fulvestrant is a pure anti-estrogen hormoal agent formally lacking any estrogen-agonist activity. We analyze the effect(s) of fulvestrant treatment on estrogen target systems in hormoe-sensitive advanced breast cancer patients. RESULTS: Patients received a median of five fulvestrant injections (range 3-19). We observed a partial response in one patient, disease stability in 21 and disease progression in 29 patients with a clinical benefit of 43.2% and a median time to progression of 5 [range 3-20] mo. Total cholesterol levels significantly decreased during treatment (219.8 +/- 45.3 vs. 201.4 +/- 42.1 mg/dl; p = 0.0054) together with LDL-cholesterol (129.7 +/- 41.39 vs. 112.3 +/- 37.1 mg/dl; p = 0.018). HDL-cholesterol and triglycerides did not show significant changes. Reduction of total and LDL-cholesterol was independent from last hormoal treatment or treatment duration. All coagulation indices and mean endometrial mucosa thickness value did not vary. METHODS: Fifty-one patients [median age 65 (range 48-82) y] were enrolled. All patients received previous hormoal treatments, with 90.2% receiving > or =2 courses. Last hormoal treatment was exemestane, letrozole, anastrozole and other in 30-10-7-4/51 patients respectively. Median withdrawal time was 18 d (range 3-1456). Complete fasting lipid blood profile and coagulation indices were assessed before fulvestrant administration, every 3 mo and at discontinuation time. Endometrial mucosa thickness was evaluated before fulvestrant administration and at end-study time. CONCLUSIONS: We observed a lipid lowering effect of fulvestrant possibly related to an influence on lipid metabolism by a mechanism in which a role could be played by progesterone receptor.
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Adenocarcinoma/secundario , Antineoplásicos Hormonales/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Colesterol/sangre , Estradiol/análogos & derivados , Moduladores de los Receptores de Estrógeno/farmacología , Estrógenos , Proteínas de Neoplasias/análisis , Neoplasias Hormono-Dependientes/secundario , Progesterona , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Adenocarcinoma/sangre , Adenocarcinoma/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/farmacología , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/sangre , Neoplasias de la Mama/patología , LDL-Colesterol/sangre , Endometrio/efectos de los fármacos , Endometrio/ultraestructura , Estradiol/farmacología , Estradiol/uso terapéutico , Moduladores de los Receptores de Estrógeno/uso terapéutico , Femenino , Fulvestrant , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/sangre , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/patología , Posmenopausia , Estudios Prospectivos , Receptores de Estrógenos/efectos de los fármacos , Receptores de Progesterona/efectos de los fármacos , Receptores de Progesterona/fisiología , Triglicéridos/sangreRESUMEN
We present a case of metastatic spreading to the testicle in a 46-year-old patient with renal cell carcinoma, "clear-cell" type, during interleukin-2 combined subcutaneous plus aerosol treatment. Testicular metastasis occurred while the patient showed a response to the treatment with disappearance of lung lesions and reduction of lymph-nodes lesions. After orchiectomy with spermatic cord resection and disease re-evaluation confirming the previous response, the patient re-started immunotherapy. The contrast between systemic disease response to treatment and disease testicular progression might be explained by a relative insensitivity of the testicle to interleukin-2 immunotherapy as a result of a possible establishment of an immunosuppressive microenvironment. We believe that the rarity of this metastatic site and the intriguing possible mechanisms at its base, makes an interesting case for clinicians.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/secundario , Interleucina-2/uso terapéutico , Neoplasias Renales/patología , Neoplasias Testiculares/secundario , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/tratamiento farmacológico , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Neoplasias Renales/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias Testiculares/diagnósticoRESUMEN
The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor aggressiveness. In this study expression of the DG subunit was evaluated by immunostaining in a series of renal epithelial cancers and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated. alphaDG expression was undetectable in a significant fraction of tumors (54%). In renal cell carcinomas (RCC) loss of alpha-DG staining correlated with higher tumor grade (p = 0.02) but not with tumor stage nor tumor size. In clear cell RCC patients loss of alphaDG staining correlated with an increased risk of recurrence (p = 0.002 by log-rank test) and death (p = 0.004) also when patients with lower grade or stage tumors were analyzed separately. In a multivariate analysis loss of DG staining confirmed to be and independent predictor of shorter disease-free (p = 0.001; RR = 4.9) and overall (p = 0.009; RR = 4.9) survival stronger than tumor grade and size. These findings demonstrate that loss of alphaDG expression, which correspond to loss of a functional DG complex, is a frequent event in human renal tumorigenesis and is an independent predictor of early recurrence and death for patients with clear cell RCC.
Asunto(s)
Carcinoma de Células Renales/metabolismo , Distroglicanos/fisiología , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/metabolismo , Proteínas de Neoplasias/fisiología , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidad , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Distroglicanos/análisis , Distroglicanos/deficiencia , Distroglicanos/genética , Femenino , Humanos , Italia/epidemiología , Estimación de Kaplan-Meier , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/deficiencia , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Bisphosphonates (BPs) delay the onset or reduce the incidence of skeletal complications in patients with bone metastases. However, there are few data on the renal safety and activity of i.v. BPs beyond 2 years of administration. MATERIALS AND METHODS: We retrospectively analyzed serum creatinine (SCr) levels and skeletal-related events (SREs) in cancer patients receiving i.v. BPs for >or= 24 months. All patients received 90 mg pamidronate every 3-4 weeks. Pre- and post-treatment SCr levels and the peak levels attained were recorded. A notable SCr increase was defined as: an increase >0.5 mg/dl for patients with baseline SCr <1.4 mg/dl; an increase >1 mg/dl for patients with baseline SCr >1.4 mg/dl; or doubling over baseline. The following parameters were also analyzed: the proportion of patients with at least one SRE, the distribution of each type of SRE, the time to first SRE, and the skeletal morbidity rate (SMR). RESULTS: Fifty-seven patients with bone metastases resulting from breast cancer (BC) (n = 48), multiple myeloma (n = 7), renal cell carcinoma (n = 1), and prostate cancer (n = 1) were evaluated. The median age at the start of treatment was 57 years (range, 27-81); 25% of the patients were >70 years old. Forty-three patients received pamidronate then switched to zoledronic acid. The median overall duration of BP administration was 34 months (range, 24+ to 131+), with a median duration of zoledronic acid therapy of 25 months (range, 2-40). Twenty-seven of 48 BC patients received different chemotherapy regimens (median number of lines, 2; range, 1-6). The median SCr levels were: baseline, 0.82 mg/dl (range, 0.4-1.4); time of analysis, 0.89 mg/dl (0.4-2); highest level, 1.0 mg/dl (0.5-2). A notable SCr increase was observed in seven patients (12.2%; all grade 1). Twenty-six patients (45.6%) experienced SREs after starting BP treatment. The median time to first SRE was 911 days (95% confidence interval, 731; 1,023). The SMR was 0.20 events per year. Ten patients ceased treatment because of: an SCr level of 2 mg/dl (n = 1) physician decision (n = 6) and jaw osteonecrosis (n = 3). Ten patients died of progressive disease. CONCLUSION: i.v. BPs are safe and active during prolonged treatment administration, and renal function is maintained in patients receiving multiple cytotoxic therapies. Jaw osteonecrosis occurred in 5% of the study population, and its causal relationship with BP treatment requires further observation and study.