RESUMEN
BACKGROUND: Wilms' tumor 1 (WT1) is overexpressed in various malignancies. DSP-7888 Dosing Emulsion, also known as ombipepimut-S (United States Adopted Name; International Nonproprietary Name: adegramotide/nelatimotide), is an investigational therapeutic cancer vaccine comprising two synthetic peptides derived from WT1 to promote both cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte-mediated immune responses against WT1-expressing tumors. OBJECTIVE: The aim of this study was to report the results from a phase I dose-escalation study (NCT02498665) that evaluated DSP-7888, administered either intradermally (ID) or subcutaneously (SC), in patients with recurrent or advanced malignancies associated with overexpression of WT1. PATIENTS AND METHODS: In this phase I dose-escalation study, patients with recurrent or advanced malignancies associated with overexpression of WT1 who progressed on, were intolerant to, or not a candidate for standard therapy or who presented with a malignancy that had no definite standard therapy received escalating doses of ID or SC DSP-7888 in a rolling-six study design. DSP-7888 3.5, 10.5, or 17.5 (ID only) mg was administered until disease progression or other discontinuation event. Primary objectives were safety, tolerability, and identification of the recommended phase II dose (RP2D). Overall survival (OS) and WT1-specific CTL induction were included as secondary and exploratory objectives, respectively. RESULTS: Twenty-four patients received either ID (3.5 mg, n = 4; 10.5 mg, n = 3; 17.5 mg, n = 3) or SC DSP-7888 (3.5 mg, n = 9; 10.5 mg, n = 5). No dose-limiting toxicity was observed. The most frequent treatment-emergent adverse event was injection site reactions (ID, 100% [10/10]; SC, 35.7% [5/14]); all were grade 1 or 2. Four patients (ID 17.5 mg, n = 1; SC 3.5 mg, n = 1; SC 10.5 mg, n = 2) had stable disease, 16 had progressive disease, and four were not evaluable. Median (95% confidence interval) OS duration was 180.0 (136.0-494.0) days. Among evaluable patients, WT1-specific CTL induction was observed in 66.7% (6/9) and 41.7% (5/12) of those administered ID and SC DSP-7888, respectively. CONCLUSIONS: DSP-7888 Dosing Emulsion was well tolerated, with no dose-limiting toxicities, in patients with recurrent or advanced malignancies. Higher WT1-specific CTL induction activity was noted with ID compared with SC administration; because of this, the ID route was selected for further evaluation in the clinical program. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02498665.
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Vacunas contra el Cáncer/uso terapéutico , Tumor de Wilms/tratamiento farmacológico , Anciano , Vacunas contra el Cáncer/farmacología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To report the outcomes of patients with favorable risk oropharyngeal cancer that underwent adjuvant radiation therapy with omission of the primary site from the clinical target volume (CTV). MATERIAL/METHODS: A retrospective study of 40 patients treated with transoral surgery (TOS) followed by neck only radiation using intensity modulated radiation therapy (IMRT) with exclusion of the primary site. For all patients, a CTV of the primary surgical bed was contoured to obtain the estimated incidental dose to the primary site. RESULTS: Median follow-up was 51 months (range, 13-155 months). The median radiation therapy (RT) dose to the neck was 6000 cGy (range, 5400-6400 cGy). The mean incidental dose to the primary tonsillar site was 4320 cGy (SD ± 480 cGy) and to the primary base of tongue site was 4060 cGy (SD ± 420 cGy). There were no local failures and only 1 regional failure, resulting in 97.5% locoregional control rate at 4 years. Two patients developed distant metastases, without evidence of locoregional recurrence, for a 4-year overall survival rate of 97%. CONCLUSIONS: Our analysis suggests that mucosal sparing RT after TOS in favorable risk oropharyngeal cancer patients may provide comparable oncologic and improved functional outcomes compared to conventional treatment in selected patients.
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Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa , Neoplasias Orofaríngeas/patología , Dosis de Radiación , Radioterapia Adyuvante , Radioterapia de Intensidad Modulada , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Genomic testing has increased the quantity of information available to oncologists. Unfortunately, many identified sequence alterations are variants of unknown significance (VUSs), which thus limit the clinician's ability to use these findings to inform treatment. We applied a combination of in silico prediction and molecular modeling tools and laboratory techniques to rapidly define actionable VUSs. MATERIALS AND METHODS: Exome sequencing was conducted on 308 tumors from various origins. Most single nucleotide alterations within gene coding regions were VUSs. These VUSs were filtered to identify a subset of therapeutically targetable genes that were predicted with in silico tools to be altered in function by their variant sequence. A subset of receptor tyrosine kinase VUSs was characterized by laboratory comparison of each VUS versus its wild-type counterpart in terms of expression and signaling activity. RESULTS: The study identified 4,327 point mutations of which 3,833 were VUSs. Filtering for mutations in genes that were therapeutically targetable and predicted to affect protein function reduced these to 522VUSs of interest, including a large number of kinases. Ten receptortyrosine kinase VUSs were selected to explore in the laboratory. Of these, seven were found to be functionally altered. Three VUSs (FGFR2 F276C, FGFR4 R78H, and KDR G539R) showed increased basal or ligand-stimulated ERK phosphorylation compared with their wild-type counterparts, which suggests that they support transformation. Treatment of a patient who carried FGFR2 F276C with an FGFR inhibitor resulted in significant and sustained tumor response with clinical benefit. CONCLUSION: The findings demonstrate the feasibility of rapid identification of the biologic relevance of somatic mutations, which thus advances clinicians' ability to make informed treatment decisions.
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Recurrent squamous cell carcinoma of the head and neck (SCCHN) carries a poor prognosis. Tumor hypoxia (TH) has been implicated as one of many factors contributing to SCCHN recurrence. TH leads to radiation resistance by reversing radiation-induced DNA damage. Effective strategies to overcome TH may improve outcomes in patients with SCCHN. We searched the English literature on PubMed and reviewed the reference sections of key articles related to TH (publications spanning from the early 1900s to the present). We summarized the underlying theory of TH in SCCHN, methods for quantifying it, and the numerous therapies developed to modulate it. We included articles that set the foundation of TH as a theory and the most relevant articles published within the last 15 years related to TH quantification and therapeutic targeting. Despite extensive research, targeting TH in SCCHN has not become a part of routine clinical practice in North America, and we analyze the pitfalls in hypoxia research that have led to this failure. We propose that future studies should test a combined approach of targeting the immune system in addition to cellular pathways rendered aberrant in TH and should include development of novel surrogate markers of TH and/or TH imaging.
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Carcinoma de Células Escamosas/complicaciones , Neoplasias de Cabeza y Cuello/complicaciones , Hipoxia Tumoral , Animales , Carcinoma de Células Escamosas/irrigación sanguínea , Carcinoma de Células Escamosas/terapia , Eritropoyetina/agonistas , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Neoplasias de Cabeza y Cuello/terapia , Humanos , Hipertermia Inducida , Oxígeno/metabolismo , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
BACKGROUND: We reviewed outcomes of patients with loco-regionally recurrent (LRR) or new primary (NP) squamous cell carcinoma of the head and neck (SCCHN) treated at our institution with reirradiation (RRT). METHODS: Patients received definitive RRT (DRRT) or post-operative RRT following salvage surgery (PRRT) from 2003 to 2011. Measured survival outcomes included loco-regional relapse free survival (LRFS) and overall survival (OS). RESULTS: Among 81 patients (PRRT, 42; DRRT, 39), median PRRT and DRRT doses were 60 Gy (12-70 Gy) and 69.6 Gy (48-76.8 Gy). The majority of patients received IMRT-based RRT (n = 77, 95 %). With median follow-up of 78.1 months (95 % CI, 56-96.8 months), 2-year OS was 53 % with PRRT and 48 % with DRRT (p = 0.12); 23 % of patients were alive at last follow-up. LRFS at 2 years was 60 %, and did not differ significantly between PRRT and DRRT groups. A trend toward inferior LRFS was noted among patients receiving chemotherapy with RRT versus RRT alone (p = 0.06). Late serious toxicities were uncommon, including osteoradionecrosis (2 patients) and carotid artery bleeding (1 patient, non-fatal). CONCLUSIONS: OS of PRRT- and DRRT-treated patients in this series appears superior to the published literature. We used IMRT for the majority of patients, in contrast to several series and trials previously reported, which may account in part for this difference. Future studies should seek to improve outcomes among patients with LRR/NP SCCHN via alternative therapeutic modalities such as proton radiotherapy and by incorporating novel systemic agents.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/radioterapia , Reirradiación/métodos , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Dosis de Radiación , Radiometría , Radioterapia/métodos , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Terapia Recuperativa , Carcinoma de Células Escamosas de Cabeza y Cuello , Resultado del TratamientoAsunto(s)
Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/terapia , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/terapia , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/terapia , Biopsia , ADN Glicosilasas/análisis , Diagnóstico Diferencial , Fatiga , Femenino , Humanos , Persona de Mediana EdadRESUMEN
PURPOSE: This first-in-human study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of single and multiple doses of TAK-441, an investigational inhibitor of the Hedgehog signaling pathway. EXPERIMENTAL DESIGN: Patients with advanced, solid tumors received daily oral TAK-441 (50-1,600 mg/day); daily dose was doubled in each subsequent cohort until the maximum tolerated/feasible dose (MTD/MFD) was reached. Blood was collected to evaluate TAK-441 plasma concentrations. Skin biopsies were obtained to evaluate suppression of the Hedgehog-regulated gene Gli1. RESULTS: Thirty-four patients were enrolled (median age 59). The most common diagnoses were colorectal cancer (26%), basal cell carcinoma (BCC, 21%), and pancreatic cancer (9%). The MFD of 1,600 mg/day (based on tablet size and strength) was considered the MTD. Dose-limiting toxicities included muscle spasms and fatigue. Grade ≥3 treatment-emergent adverse events, regardless of causality, occurred in 15 patients (44%), of which hyponatremia (n = 4) and fatigue (n = 3) were most common. Oral absorption was fairly rapid; median Tmax was 2.0 to 4.0 hours after a single dose. Mean elimination half-life was 13.5 to 22.6 hours. Systemic exposure of TAK-441 based on the area under the plasma concentration-time curve was linear across the dose range. Gli1 expression in skin biopsies was strongly inhibited at all dose levels. Best response was partial response (1 patient with BCC) and stable disease (7 patients with various solid tumors). CONCLUSIONS: TAK-441 was generally well tolerated up to MFD of 1,600 mg/day, with preliminary antitumor activity. Further study of TAK-441 may be appropriate in populations selected for tumors with ligand-dependent or independent Hedgehog signaling.
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Antineoplásicos/uso terapéutico , Proteínas Hedgehog/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Piridinas/uso terapéutico , Pirroles/uso terapéutico , Transducción de Señal/efectos de los fármacos , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Progresión de la Enfermedad , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Estadificación de Neoplasias , Neoplasias/diagnóstico , Neoplasias/genética , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/farmacocinética , Pirroles/administración & dosificación , Pirroles/efectos adversos , Pirroles/farmacocinética , ARN Mensajero/genética , Retratamiento , Factores de Transcripción/genética , Resultado del Tratamiento , Proteína con Dedos de Zinc GLI1RESUMEN
PURPOSE: To conduct a phase I study determining the safety, pharmacokinetics and preliminary efficacy of EP-100, a novel anticancer drug consisting of natural luteinizing-hormone-releasing hormone (LHRH) ligand linked to a cationic membrane-disrupting peptide. METHODS: Patients with advanced, solid tumors, positive for LHRH receptor by immunohistochemistry (IHC), received EP-100 weekly or twice weekly for 3 of 4 weeks in a 28 day cycle. A modified Fibonacci 3 + 3 dose-escalation schema was used. Initial cohorts received EP-100 once weekly (cohorts 1-7, 0.6-7.8 mg/m(2), n = 21). Later cohorts received doses twice weekly (cohorts 7-11, 7.8-40 mg/m(2), n = 16). RESULTS: LHRH-receptor expression was confirmed by IHC in 52 of 89 consented patients; 37 patients received at least 1 dose. Cohorts receiving doses of 5.2 mg/m(2) and above achieved therapeutic levels from in vitro studies Clearance was rapid (mean half-life 7.1 ± 3.8 to 15.9 ± 3.6 min). The maximum-tolerated dose was not reached at the highest dose evaluated (40 mg/m(2) twice weekly). Grade 2 increase in alanine aminotransferase/serum aspartate aminotransferase in one patient resolved, did not recur upon re-treatment, and was not observed in other patients. The only drug-related adverse event was transient infusion-related dermatologic reactions (10 patients). No complete or partial tumor responses were observed; seven patients had stable disease of 16 weeks. CONCLUSIONS: EP-100 was well tolerated in patients with advanced, LHRH-receptor-expressing solid tumors. The recommended phase 2 dose is 40 mg/m(2) twice weekly for 3 of 4 weeks per cycle.
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Neoplasias/tratamiento farmacológico , Receptores LHRH/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Estudios de Cohortes , Femenino , Semivida , Humanos , Masculino , Dosis Máxima Tolerada , Neoplasias/metabolismo , Neoplasias/patología , Receptores LHRH/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to report the treatment outcomes of patients with advanced oropharyngeal cancer treated with transoral laser microsurgery (TLM) followed by radiation therapy (RT) at Mayo Clinic in Arizona. METHODS: A retrospective study of 80 patients treated from January 1, 2000 to November 7, 2011 was performed. All patients had stage III/IV oropharyngeal tumors and underwent TLM with neck dissection. Adjuvant RT was then given. Thirty-seven patients received concurrent adjuvant chemotherapy. The primary outcome was locoregional control. RESULTS: Median follow-up was 47.3 months (range, 9.7-139.2 months). The 3-year locoregional control, recurrence-free survival, and overall survival rates were 98.6% (95% confidence interval [CI], 91% to 100%), 91.1% (95% CI, 81% to 96%), and 93.7% (95% CI, 84% to 98%), respectively. There were a total of 5 treatment failures, 1 regional and 4 distant. Twenty-six patients underwent neck only RT with exclusion of the primary site. CONCLUSION: TLM followed by RT for advanced oropharyngeal cancer results in excellent locoregional control rates.
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Terapia por Láser , Microcirugia , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirugía , Radioterapia Adyuvante , Centros Médicos Académicos , Adulto , Anciano , Anciano de 80 o más Años , Arizona , Femenino , Estudios de Seguimiento , Humanos , Masculino , Microcirugia/métodos , Persona de Mediana Edad , Neoplasias Orofaríngeas/patología , Cuidados Posoperatorios , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
UNLABELLED: Concomitant medication (CM) use may result in Phase I cancer clinical trial ineligibility due to concern for potential CM-investigational drug interactions or alteration of investigational drug absorption. Few studies have examined the impact of CM use on trial eligibility. METHODS: We reviewed records of 274 patients on Phase I trials at a single academic institution. Demographics, CM identities and classes, CM discontinuation, reasons, and incidence of CM substitution were recorded. CM-investigational drug cytochrome P450 (CYP) enzyme interactions were documented. Statistical analysis was performed using descriptive statistics. RESULTS: 273 of 274 patients (99.6%, 95% confidence interval [CI] 98.9-100%) took CM, with a median of 8 CM per patient (range 0 - 42). CM discontinuation occurred in 67 cases (25%, 95% CI 19-30%). The most common CM classes discontinued were herbal (17 cases, 25%, 95% CI 16-37%) and proton pump inhibitors (15 cases, 22%, 95% CI 12-32%). CM discontinuation reasons were: protocol prohibition (32 cases, 48%, 95% CI 36-60%); potential CM-investigational drug interaction (25 cases, 37%, 95% CI 26-49%); other (10 cases, 15%, 95% CI 6-23%). A potential CM-investigational drug CYP interaction was noted in 122 cases (45%, 95% CI 39-50%). CM potentially weakly decreased investigational drug metabolism in 52 cases (43%, 95% CI 34-51%), and potentially strongly decreased investigational drug metabolism in 17 cases (14%, 95% CI 8-20%). Investigational drug potentially weakly decreased CM metabolism in 39 cases (32%, 95% CI 24-40%), and potentially strongly decreased CM metabolism in 28 cases (23%, 95% CI 15-30%). CM substitution occurred in 36/67 cases (54%, 95% CI 41-66%) where CM were discontinued to allow for eventual participation in clinical trials. Overall in 2 cases (0.7%, 95% CI 0.1-2.6%), patients were protocol ineligible because CM could not be discontinued or substituted. CONCLUSIONS: This study highlights the high prevalence of concomitant medication use among cancer patients enrolled in phase I clinical trials. Most patients did meet trial eligibility criteria with careful substitution and discontinuation of CM. The most common reason for discontinuation of CM was protocol prohibition. The most common medications discontinued were herbal, proton pump inhibitors, selective serotonin reuptake inhibitor anti-depressants, and non-steroidal anti-inflammatory drugs.
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BACKGROUND: Neoadjuvant chemoradiation (NCR) prior to resection of extremity soft tissue sarcoma (STS) has been studied, but data are limited. We present outcomes with NCR using a variety of chemotherapy regimens compared to neoadjuvant radiation without chemotherapy (NR) and surgery alone (SA). METHODS: We conducted a retrospective chart review of 112 cases. RESULTS: Treatments included SA (36 patients), NCR (39 patients), and NR (37 patients). NCR did not improve the rate of margin-negative resections over SA or NR. Loco-regional relapse-free survival, distant metastases-free survival, and overall survival (OS) were not different among the treatment groups. Patients with relapsed disease (OR 11.6; p = 0.01), and tumor size greater than 5 cm (OR 9.4; p = 0.01) were more likely to have a loco-regional recurrence on logistic regression analysis. Significantly increased OS was found among NCR-treated patients with tumors greater than 5 cm compared to SA (3 year OS 69 vs. 40%; p = 0.03). Wound complication rates were higher after NCR compared to SA (50 vs. 11%; p = 0.003) but not compared to NR (p = 0.36). Wet desquamation was the most common adverse event of NCR. CONCLUSIONS: NCR and NR are acceptable strategies for patients with STS. NCR is well-tolerated, but not clearly superior to NR.
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Quimioradioterapia/métodos , Terapia Neoadyuvante/métodos , Radioterapia/métodos , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/radioterapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia , Análisis de Regresión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Topotecan pharmacokinetics at higher infusion rates (4 mg/m2 over 30 minutes) have not been studied. The authors report a pharmacokinetics and safety study of this dose in advanced cancer patients. Sixteen patients were given a 4-mg/m2 topotecan infusion intravenously (IV) over 30 minutes weekly for 3 weeks, repeated every 28 days. Pharmacokinetics were determined after the first dose. Plasma concentrations of total topotecan were measured to derive CL, V(ss), C(max), t(max), t(1/2), AUC(0-t), and AUC(0-infinity). Plasma total topotecan concentrations decreased biexponentially, with a mean CL value of 20.6 L/h, V(ss) value of 101 L, and t(1/2) value of 5.0 h. Nine significant adverse events (all hematologic) were topotecan related. Grade 3 or less adverse events included anemia, thrombocytopenia, leukopenia, and fatigue. Pharmacokinetics of the 4-mg/m2 infusion of topotecan over 30 minutes are comparable to findings from studies of lower and higher doses. Toxicities are similar to previous reports.
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Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Tolerancia a Medicamentos , Neoplasias/tratamiento farmacológico , Topotecan/efectos adversos , Topotecan/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Anemia/inducido químicamente , Antineoplásicos/administración & dosificación , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Fatiga/inducido químicamente , Femenino , Humanos , Infusiones Intravenosas , Leucopenia/inducido químicamente , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Trombocitopenia/inducido químicamente , Topotecan/administración & dosificaciónRESUMEN
OBJECTIVE: Haemoglobin levels often decline into the anaemic range with androgen deprivation therapy (ADT). We conducted a chart review of patients receiving ADT for metastatic prostate cancer to assess anaemia-related symptoms. METHODS: 135 stage IV prostate cancer cases were reviewed for treatment type; haemoglobin values before and after treatment; and symptoms of anaemia. Mean haemoglobin levels before and after for all treatment forms, for leuprolide alone, and for combination leuprolide/bicalutamide were calculated and evaluated for significant differences. The numbers of patients developing symptoms were recorded and the effects of specific therapies evaluated. RESULTS: For all ADT treated patients, mean haemoglobin declined by -1.11 g/dL (p<.0001). Leuprolide-alone treated patients had a mean decline of -1.66 g/dL (p<0.0001). Leuprolide and bicalutamide combination treatment caused a mean decline of -0.78 g/dL (p=0.0426). 16 of 43 patients had anemia symptoms. Contingency analysis with Fisher's exact test shows patients receiving leuprolide therapy alone versus other forms of ADT were significantly less likely to have symptoms (chi(2)=0.0190). CONCLUSIONS: The present study confirms that ADT results in a significant drop in haemoglobin levels into the anaemic range. A number of patients become symptomatic from this change. Practitioners should monitor haemoglobin levels, and treat symptomatic patients.
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Antagonistas de Andrógenos/efectos adversos , Anemia/inducido químicamente , Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Antagonistas de Andrógenos/uso terapéutico , Anemia/terapia , Anilidas/efectos adversos , Anilidas/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Terapia Combinada , Goserelina/efectos adversos , Goserelina/uso terapéutico , Hemoglobinas/análisis , Humanos , Leuprolida/efectos adversos , Leuprolida/uso terapéutico , Modelos Lineales , Masculino , Metástasis de la Neoplasia , Nitrilos/efectos adversos , Nitrilos/uso terapéutico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Compuestos de Tosilo/efectos adversos , Compuestos de Tosilo/uso terapéuticoRESUMEN
A vaccine for the prevention of herpes zoster outbreaks in adults over the age of 60 years has recently been approved. A 76-year-old white female with a history of recurrent left axillary breast cancer undergoing chemotherapy was given a Zostavax injection by her primary care physician. Eight days later, the patient developed a rash. Given the recent administration of live, attenuated varicella zoster virus (VZV), a diagnosis of disseminated cutaneous herpes zoster was made. The patient was treated successfully with a course of famciclovir for 10 days and cephalexin for 7 days for a secondary bacterial infection. A review of the medical literature disclosed no reports of Zostavax given to adult cancer patients immunocompromised by systemic chemotherapy. Therefore, we believe this report is the first to describe the consequences of Zostavax administration to such a host. Clinicians should take care to review contraindications and precautions prior to administering the Zostavax vaccine.
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Vacuna contra el Herpes Zóster/efectos adversos , Herpes Zóster/etiología , Herpesvirus Humano 3/patogenicidad , Huésped Inmunocomprometido/inmunología , Vacunas Atenuadas/efectos adversos , Anciano , Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Contraindicaciones , Femenino , Herpesvirus Humano 3/inmunología , Humanos , Médicos de FamiliaAsunto(s)
Trastornos de la Articulación/virología , Enfermedades Virales del Sistema Nervioso Central/complicaciones , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Anciano , Antivirales/uso terapéutico , Enfermedades Virales del Sistema Nervioso Central/tratamiento farmacológico , Herpes Zóster/tratamiento farmacológico , Humanos , MasculinoRESUMEN
Androgen deprivation therapy (ADT) is a commonly used treatment for metastatic prostate cancer. A 78-year-old patient with metastatic prostate cancer had transfusion-dependent anemia develop while on ADT. The patient also had hereditary hemorrhagic telangiectasia (HHT), with chronic gastrointestinal blood loss. Blood transfusions were required every 3 weeks for 4 months to keep hemoglobin levels above 8 g/dL, despite discontinuation of ADT. The anemia, which had been well managed with iron therapy before ADT, was worsened by the loss of bone marrow-stimulating testosterone effects. The case highlights testosterone's important role in erythrocyte production. Practitioners should monitor hemoglobin levels in patients undergoing ADT.