RESUMEN
BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1. In a subgroup analysis of patients with advanced UC participating in a phase I/II study, epacadostat-pembrolizumab treatment produced an objective response rate (ORR) of 35%. METHODS: ECHO-303/KEYNOTE-698 was a double-blinded, randomized phase III study of adults with metastatic or unresectable locally advanced UC with recurrence or progression following first-line platinum-based chemotherapy. Participants were randomized to epacadostat 100 mg twice daily (BID) plus pembrolizumab or placebo plus pembrolizumab until completion of 35 pembrolizumab infusions, disease progression, or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Target enrollment was 648 patients; enrollment was halted early based on efficacy results from the phase III ECHO-301/KEYNOTE-252 study in metastatic melanoma. Forty-two patients were randomized to each treatment arm. Median duration of follow-up was 62 days in each arm. The investigator-assessed ORR (unconfirmed) was 26.2% (95% CI 16.35-48.11) for epacadostat plus pembrolizumab and 11.9% (95% CI 4.67-29.50) for placebo plus pembrolizumab. Two complete responses were reported, both in the placebo-plus-pembrolizumab arm. Circulating kynurenine levels increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and numerically decreased in the epacadostat-plus-pembrolizumab arm. The safety profile of epacadostat plus pembrolizumab was similar to that of pembrolizumab monotherapy, although a numerically greater proportion of patients in the combination vs. control arm experienced treatment-related grade ≥ 3 adverse events (16.7% vs. 7.3%). One patient in each arm died due to cardiovascular events, which were not deemed drug-related. No new safety concerns were identified for either agent. CONCLUSIONS: Epacadostat plus pembrolizumab demonstrated anti-tumor activity and was generally tolerable as second-line treatment of patients with unresectable locally advanced or recurrent/progressive metastatic UC. Epacadostat 100 mg BID, when administered with pembrolizumab, did not normalize circulating kynurenine in most patients. Further study of combined IDO1/PD-L1 inhibition in this patient population, particularly with epacadostat doses that result in durable normalization of circulating kynurenine, may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374488. Registered 12/15/2017.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Sulfonamidas , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Persona de Mediana Edad , Método Doble Ciego , Sulfonamidas/administración & dosificación , Sulfonamidas/uso terapéutico , Oximas/administración & dosificación , Oximas/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Anciano de 80 o más Años , Adulto , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Indoleamine 2,3- dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been correlated with shorter disease-specific survival in patients with urothelial carcinoma (UC). IDO1 may counteract the antitumor effects of immune checkpoint inhibitors. Epacadostat is a potent and highly selective inhibitor of IDO1. In the phase I/II ECHO-202/KEYNOTE-037 study, epacadostat plus pembrolizumab resulted in a preliminary objective response rate (ORR) of 35% in a cohort of patients with advanced UC. METHODS: ECHO-307/KEYNOTE-672 was a double-blinded, randomized, phase III study. Eligible adults had confirmed locally advanced/unresectable or metastatic UC of the urinary tract and were ineligible to receive cisplatin-based chemotherapy. Participants were randomly assigned (1:1) to receive epacadostat (100 mg twice daily) plus pembrolizumab (200 mg every 3 weeks) or placebo plus pembrolizumab for up to 35 pembrolizumab infusions. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (version 1.1). RESULTS: A total of 93 patients were randomized (epacadostat plus pembrolizumab, n = 44; placebo plus pembrolizumab, n = 49). Enrollment was stopped early due to emerging data from the phase III ECHO-301/KEYNOTE-252 study. The median duration of follow-up was 64 days in both arms. Based on all available data at cutoff, ORR (unconfirmed) was 31.8% (95% CI, 22.46-55.24%) for epacadostat plus pembrolizumab and 24.5% (95% CI, 15.33-43.67%) for placebo plus pembrolizumab. Circulating kynurenine levels numerically increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and decreased in the epacadostat-plus-pembrolizumab arm. Epacadostat-plus-pembrolizumab combination treatment was well tolerated with a safety profile similar to the placebo arm. Treatment discontinuations due to treatment-related adverse events were more frequent with epacadostat (11.6% vs. 4.1%). CONCLUSIONS: Treatment with epacadostat plus pembrolizumab resulted in a similar ORR and safety profile as placebo plus pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced/unresectable or metastatic UC. At a dose of 100 mg twice daily, epacadostat did not appear to completely normalize circulating kynurenine levels when administered with pembrolizumab. Larger studies with longer follow-up and possibly testing higher doses of epacadostat, potentially in different therapy settings, may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03361865, retrospectively registered December 5, 2017.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Sulfonamidas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Masculino , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Cisplatino/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Método Doble Ciego , Persona de Mediana Edad , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Anciano de 80 o más Años , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Adulto , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , OximasRESUMEN
Muscle-invasive bladder cancer (MIBC) is associated with high rates of recurrence and poor prognosis despite aggressive treatment. Neoadjuvant chemotherapy before radical cystectomy (RC) improves outcomes in cisplatin-eligible patients; however, the improvement in overall survival is modest. Standard of care for cisplatin-ineligible patients remains RC; more effective systemic therapies are needed. Recent Phase Ib/II studies suggest pembrolizumab monotherapy and combination therapy are effective neoadjuvant therapies for MIBC. The randomized Phase III KEYNOTE-866 and KEYNOTE-905/EV-303 studies are being conducted to evaluate efficacy and safety of perioperative pembrolizumab or placebo with chemotherapy in cisplatin-eligible patients with MIBC (KEYNOTE-866) and of pembrolizumab monotherapy versus pembrolizumab plus enfortumab vedotin versus RC plus pelvic lymph node dissection alone in cisplatin-ineligible patients with MIBC (KEYNOTE-905/EV-303). Clinical trial registration: NCT03924856 & NCT03924895 (ClinicalTrials.gov).
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Terapia Neoadyuvante/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , HumanosRESUMEN
PURPOSE: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K. METHODS: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono). Exploratory patient-reported outcomes (PROs) were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Brief Pain Inventory Short Form (BPI-SF) at baseline, once per week for cycles 1-3, and then in every cycle through the end of treatment. Changes in scores from baseline to week 24, reported as least squares mean (standard error), were assessed by mixed models for repeated measures. There were no formal statistical comparisons between treatment arms. RESULTS: Of 149 patients treated, 65 (EV + P) and 63 (EV mono) comprised the PRO analysis set. For EV + P, EORTC QLQ-C30 QOL was maintained through week 24 with improvements in emotional functioning, pain, and insomnia. Clinically meaningful improvements were seen in EORTC QLQ-C30 pain after EV + P at weeks 12 (-14.41 [3.14]) and 24 (-14.99 [3.56]) and BPI-SF worst pain at week 24 (-2.07 [0.37]). For EV mono, EORTC QLQ-C30 QOL remained stable with clinically meaningful improvements in EORTC QLQ-C30 pain (-12.55 [4.27]), insomnia (-14.46 [4.69]), and constipation (-10.09 [4.35]) at week 24. There were small-to-moderate improvements in BPI-SF worst pain at week 24. CONCLUSION: EV + P in patients with la/mUC who were cisplatin-ineligible was associated with preservation or improvement of QOL/functioning/symptoms. Improvement in pain was seen in both PRO instruments and treatment arms. These data complement clinical outcomes of 1L EV + P.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Carcinoma de Células Transicionales , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Cisplatino , Dolor , Medición de Resultados Informados por el Paciente , Calidad de Vida/psicologíaRESUMEN
This study tested the hypothesis that various components of the stress process model were related to negative outcomes (depression, guilt, negative health) in cancer caregivers. This study also tested the hypothesis that psychosocial resources (mastery, socioemotional support) mediated the relationship between the various domains of the stress process model and negative outcomes. A total of 238 cancer caregivers were recruited from radiation medicine clinics at the University of Maryland Greenebaum Cancer Center (n = 186) and the University of Minnesota Cancer Center (n = 52). A comprehensive interview battery was administered. A multivariate regression found that primary subjective stressors were the strongest predictors of depression and negative health impact. A path analysis indicated that mastery mediated the relationship between role captivity and negative health impact. These results emphasize the importance of multidimensional assessment in cancer caregiving. The findings also suggest refinements to the stress process model when examining family cancer care.
Asunto(s)
Cuidadores/psicología , Neoplasias/enfermería , Apoyo Social , Estrés Psicológico/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Depresión/prevención & control , Depresión/psicología , Enfermería de la Familia , Femenino , Culpa , Estado de Salud , Humanos , Masculino , Maryland , Persona de Mediana Edad , Minnesota , Modelos Psicológicos , Análisis Multivariante , Análisis de Regresión , Estrés Psicológico/psicologíaRESUMEN
PURPOSE: To determine the maximum tolerated dose of upper abdominal low-dose fractionated radiotherapy (<1.0 Gy per fraction) given in combination with, and as a chemopotentiator for, gemcitabine. METHODS AND MATERIALS: Gemcitabine was given at 1,250 mg/m(2) at 10 mg/m(2)/min on Days 1 and 8 of a 3-week cycle. Low-dose fractionated radiotherapy was tested at two dose levels: 60 cGy per fraction and 70 cGy per fraction. Radiotherapy was given b.i.d. on Days 1, 2, 8, and 9. Four cycles were planned. RESULTS: Twenty-seven patients have been put on study. Ten patients have been entered in Phase I: 6 with metastatic/recurrent pancreatic carcinoma and 4 with unresectable pancreatic/small bowel carcinoma. Two of four patients at Dose Level 2 experienced dose-limiting toxicity. The overall radiographic response was 30%, and median survival was 11 months (range, 4-37 months). CONCLUSION: Low-dose fractionated radiotherapy to the upper abdomen is well tolerated at 60 cGy per fraction when combined with gemcitabine. Phase II evaluation is ongoing.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Intestinales/tratamiento farmacológico , Neoplasias Intestinales/radioterapia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Fraccionamiento de la Dosis de Radiación , Esquema de Medicación , Femenino , Humanos , Neoplasias Intestinales/mortalidad , Intestino Delgado , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Fármacos Sensibilizantes a Radiaciones/efectos adversos , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , GemcitabinaRESUMEN
New chemical entities, steroidal C-17 benzoazoles (5, 6, 9 and 10) and pyrazines (14 and 15) were rationally designed and synthesized. The key reaction for synthesis of the benzoazoles involved the nucleophilic vinylic "addition-elimination" substitution reaction of 3beta-acetoxy-17-chloro-16-formylandrosta-5,16-diene (2) and benzoazole nucleophiles, while that for synthesis of pyrazines involved palladium-catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3beta-ol (13) with tributylstannyl diazines. Some of the compounds were shown to be potent inhibitors of human CYP17 enzyme as well as potent antagonist of both wild type and mutant androgen receptors (AR). The most potent CYP17 inhibitors were 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (5, code named VN/124-1), 3beta-hydroxy-17-(5(1)-pyrimidyl)androsta-5,16-diene (15) and 17-(1H-benzimidazole-1-yl)androsta-4,16-dien-3-one (6), with IC(50) values of 300, 500 and 915 nM, respectively. Compounds 5, 6, 14 and 15 were effective at preventing binding of (3)H-R1881 (methyltrienolone, a stable synthetic androgen) to both the mutant LNCaP AR and the wild-type AR, but with a 2.2- to 5-fold higher binding efficiency to the latter. Compounds 5 and 6 were also shown to be potent pure AR antagonists. The cell growth studies showed that 5 and 6 inhibit the growth of DHT-stimulated LNCaP and LAPC4 prostate cancer cells with IC(50) values in the low micromolar range (i.e., <10 microM). Their inhibitory potencies were comparable to that of casodex but remarkably superior to that of flutamide. The pharmacokinetics of compounds 5 and 6 in mice were investigated. Following s.c. administration of 50 mg/kg of 5 and 6, peak plasma levels of 16.82 and 5.15 ng/mL, respectively, occurred after 30 to 60 min, both compounds were cleared rapidly from plasma (terminal half-lives of 44.17 and 39.93 min, respectively), and neither was detectable at 8 h. Remarkably, compound 5 was rapidly converted into a metabolite tentatively identified as 17-(1H-benzimidazol-1-yl)androsta-3-one. When tested in vivo, 5 proved to be very effective at inhibiting the growth of androgen-dependent LAPC4 human prostate tumor xenograft, while 6 was ineffective. Compound 5 (50 mg/kg/twice daily) resulted in a 93.8% reduction (P = 0.00065) in the mean final tumor volume compared with controls, and it was also significantly more effective than castration. To our knowledge, this is the first example of an antihormonal agent (an inhibitor of androgen synthesis (CYP17 inhibitor)/antiandrogen) that is significantly more effective than castration in suppression of androgen-dependent prostate tumor growth. In view of these impressive anticancer properties, compound 5 is a strong candidate for development for the treatment of human prostate cancer.
Asunto(s)
Antagonistas de Andrógenos/síntesis química , Androstadienos/síntesis química , Antineoplásicos/síntesis química , Azoles/síntesis química , Bencimidazoles/síntesis química , Neoplasias de la Próstata/tratamiento farmacológico , Pirazinas/síntesis química , Esteroide 17-alfa-Hidroxilasa/antagonistas & inhibidores , Inhibidores de 5-alfa-Reductasa , Antagonistas de Andrógenos/química , Antagonistas de Andrógenos/farmacología , Androstadienos/farmacocinética , Androstadienos/farmacología , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Azoles/farmacocinética , Azoles/farmacología , Bencimidazoles/farmacocinética , Bencimidazoles/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Isoenzimas/antagonistas & inhibidores , Masculino , Ratones , Ratones SCID , Mutación , Pirazinas/farmacocinética , Pirazinas/farmacología , Ensayo de Unión Radioligante , Receptores Androgénicos/efectos de los fármacos , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Relación Estructura-Actividad , Distribución Tisular , Transcripción Genética/efectos de los fármacos , Activación Transcripcional/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A facile preparation of azolyl steroids, VN/85-1 and VN/87-1 (potent inhibitors of CYP17) has been developed. This process without tedious chromatographic separations improved the overall yields from 55 and 45% to 70 and 65% for VN/85-1 and VN/87-1, respectively. Pharmacokinetic studies of VN/85-1 were conducted in male SCID mice. Following subcutaneous (s.c.) administration of 100mg/kg of VN/85-1, peak plasma level of 16.73 microg/ml occurred after 45 min, and the compound was cleared rapidly with a t(1/2) of 52.34 min. The bioavailability of VN/85-1 after s.c. administration was 83.0%. VN/85-1 was also rapidly metabolized to the corresponding 3-oxo-4-ene analog, 17-(1H-imidazol-1-yl)androsta-4,16-diene-3-one (VN/108-1). In our attempt to optimize the anti-tumor efficacy of these two CYP17 inhibitors, we studied their anti-tumor efficacies in male SCID mice bearing LNCaP tumor xenografts, utilizing various drug doses and drug scheduling. Three times a day dose regimen (3 x dose regimen) of VN/85-1 was more effective than a once daily dose. In contrast, 3 x dose regimen doses of VN/87-1 were less effective than the once daily dose. However, at their effective dosage regimes, VN/85-1 and VN/87-1 were each as effective as castration and more effective than finasteride or casodex, an anti-androgen used for prostate cancer (PC) therapy. For all of the treatments, there was a strong correlation between the tumor volumes and other associated parameters, such as, tumor weights, and serum testosterone (T) and PSA levels. These results indicate that VN/85-1 or VN/87-1 may be useful in the treatment of hormone-dependent prostate cancer.
Asunto(s)
Androstadienos/farmacocinética , Androstanoles/farmacocinética , Imidazoles/farmacocinética , Neoplasias de la Próstata/tratamiento farmacológico , Esteroide 17-alfa-Hidroxilasa/antagonistas & inhibidores , Triazoles/farmacocinética , Androstadienos/farmacología , Androstanoles/farmacología , Animales , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Finasterida/farmacología , Humanos , Imidazoles/farmacología , Masculino , Ratones , Ratones SCID , Neoplasias de la Próstata/enzimología , Factores de Tiempo , Trasplante Heterólogo , Triazoles/farmacologíaRESUMEN
PURPOSE: We report the long-term results of a prospective, Phase II study of long-term androgen deprivation (AD), pelvic radiotherapy (EBRT), permanent transperineal prostate brachytherapy boost (PB), and adjuvant docetaxel in patients with high-risk prostate cancer. METHODS AND MATERIALS: Eligibility included biopsy-proven prostate adenocarcinoma with the following: prostate-specific antigen (PSA) > 20 ng/ml; or Gleason score of 7 and a PSA >10 ng/ml; or any Gleason score of 8 to 10; or stage T2b to T3 irrespective of Gleason score or PSA. Treatment consisted of 45 Gy of pelvic EBRT, followed 1 month later by PB with either iodine-125 or Pd-103. One month after PB, patients received three cycles of docetaxel chemotherapy (35 mg/m(2) per week, Days 1, 8, and 15 every 28 days). All patients received 2 years of AD. Biochemical failure was defined as per the Phoenix definition (PSA nadir + 2). RESULTS: From August 2000 to March 2004, 42 patients were enrolled. The median overall and active follow-ups were 5.6 years (range, 0.9-7.8 years) and 6.3 years (range, 4-7.8 years), respectively. Grade 2 and 3 acute genitourinary (GU) and gastrointestinal (GI) toxicities were 50.0% and 14.2%, respectively, with no Grade 4 toxicities noted. Grade 3 and 4 acute hematologic toxicities were 19% and 2.4%, respectively. Of the patients, 85.7% were able to complete the planned multimodality treatment. The 5- and 7-year actuarial freedom from biochemical failures rates were 89.6% and 86.5%, and corresponding rates for disease-free survival were 76.2% and 70.4%, respectively. The 5- and 7-year actuarial overall survival rates were 83.3% and 80.1%, respectively. The 5- and 7-year actuarial rates of late Grade 2 GI/GU toxicity (no Grade 3-5) was 7.7%. CONCLUSIONS: The trimodality approach of using 2 years of AD, external radiation, brachytherapy, and upfront docetaxel in high-risk prostate cancer is well tolerated, produces encouraging long-term results, and should be validated in a multi-institutional setting.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Antineoplásicos/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Taxoides/administración & dosificación , Adenocarcinoma/sangre , Adenocarcinoma/patología , Anciano , Antagonistas de Andrógenos/uso terapéutico , Braquiterapia/efectos adversos , Braquiterapia/métodos , Quimioterapia Adyuvante/métodos , Supervivencia sin Enfermedad , Docetaxel , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pelvis , Estudios Prospectivos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Radioterapia/efectos adversos , Radioterapia/métodosRESUMEN
GOALS OF WORK: The objective of this study was to examine whether employment status and gender was associated with family cancer caregivers' reports of stress and well-being. MATERIALS AND METHODS: Using a correlational, cross-sectional survey design, this study included 183 primary caregivers (i.e., those individuals who provided the most help to persons with cancer). Caregivers were recruited in a radiation oncology cancer clinic and were administered detailed interviews that collected a wide range of information about the stress process. RESULTS: Bivariate and multivariable analyses suggested a number of differences between various classifications of employment status and gender. In particular, women who worked appeared more likely to provide instrumental care to the person with cancer when compared to men who did or did not work. In addition, women who worked were more likely to report feelings of exhaustion and fatigue when compared to men who worked. CONCLUSIONS: The results emphasize the need to consider the context of cancer care when analyzing the stress process. When faced with employment, women appear particularly at risk for emotional distress and greater perceived care demands. Utilizing tools that identify cancer caregivers at risk based on work, gender, or other contextual variables may inform the development and targeting of clinical interventions for this population.
Asunto(s)
Cuidadores/psicología , Neoplasias/enfermería , Estrés Psicológico/psicología , Adulto , Anciano , Estudios Transversales , Empleo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Calidad de Vida/psicología , Factores SexualesRESUMEN
Few studies examine how cancer caregiving stress "proliferates," or how stress related to care provision spreads and influences other aspects of life. These other aspects of life are called secondary stressors and may include perceptions of family support, financial strain, or the caregiver's schedule. In the current study, data on sociodemographic background, care demands, and psychosocial stress were collected from 186 cancer caregivers. A multivariate regression analysis was used to identify factors reliably related to secondary stressors. Role overload appeared to exacerbate multiple secondary stressors, whereas socioemotional support protected caregivers against all dimensions of secondary stress. These empirical results are among the first on predictors of secondary stress in cancer caregiving, and they may inform future descriptive and clinical examinations of the stress process in cancer caregiving families.
Asunto(s)
Cuidadores/psicología , Neoplasias/psicología , Estrés Psicológico/complicaciones , Actividades Cotidianas , Femenino , Encuestas Epidemiológicas , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Psicometría , Factores de Riesgo , Apoyo Social , Estrés Psicológico/etiologíaRESUMEN
Although research has emerged documenting the psychosocial impact of family care for cancer patients, few efforts capture the multi-dimensional nature of cancer caregiving stress, particularly among socioeconomically diverse samples. Utilizing data collected from cancer caregivers at a non-urban, Southern US site and an inner-city, Northeastern US site (N=233), the present study identified predictors of multiple dimensions of caregivers' subjective stress (i.e. emotional appraisals of care demands). Various indicators representing the sociodemographic context of care, cancer care demands, and psychosocial resources were found to exacerbate or buffer caregivers from feelings of exhaustion, role entrapment, and loss of intimacy with the cancer patient. The multivariate regression model also emphasized the diffuse yet potent role care recipient mood problems and caregiver mastery/optimism have on multiple dimensions of subjective stress. The findings offer a number of recommendations for future research and practice focused on informal cancer care.