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1.
Breast Cancer Res Treat ; 175(1): 5-15, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30671765

RESUMEN

PURPOSE: Diarrhea is recognized as a common adverse event associated with tyrosine kinase inhibitors (TKIs), with those targeting the ErbB family of receptors being associated with the highest rate of diarrhea. METHODS: This paper reviews data on the incidence, timing, and duration of diarrhea associated with US Food and Drug Administration-approved ErbB family-targeted TKIs from the published literature, and sets forth recommendations for management. RESULTS: In the absence of anti-diarrheal prophylaxis the incidence of any-grade diarrhea varies and typically occurs early during the course of treatment. Although it is difficult to determine if the incidence and severity of diarrhea is related to inhibition of a particular kinase target because of the multi-targeted and overlapping activity of many agents, evidence suggests that second-generation TKIs with broader target profiles (i.e., afatinib, lapatinib, neratinib) result in a higher incidence of diarrhea compared with highly specific first- (erlotinib, gefitinib) or third- (osimertinib) generation agents. The mechanisms responsible for TKI-associated diarrhea are not fully understood and are likely multi-factorial, involving dysregulated ion transport, inflammation, and mucosal injury. Management strategies have been developed-and continue to be refined-to prevent and reduce the severity and duration of TKI-associated diarrhea. For agents associated with more significant symptoms, anti-diarrheal prophylaxis reduces the incidence and severity of diarrhea, and ongoing studies are evaluating specific strategies to further reduce incidence and duration of TKI-associated diarrhea. CONCLUSIONS: Continued investigations into risk factors and pharmacogenomic markers for diarrhea may further improve management of this common toxicity.


Asunto(s)
Antineoplásicos/efectos adversos , Diarrea/diagnóstico , Diarrea/etiología , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Diagnóstico Diferencial , Diarrea/epidemiología , Diarrea/terapia , Manejo de la Enfermedad , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Profilaxis Posexposición , Inhibidores de Proteínas Quinasas/uso terapéutico , Índice de Severidad de la Enfermedad , Factores de Tiempo
2.
Breast Cancer Res Treat ; 164(3): 649-658, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28508185

RESUMEN

PURPOSE: Ixabepilone is a microtubule stabilizer with activity in taxane-refractory metastatic breast cancer and low susceptibility to taxane-resistance mechanisms including multidrug-resistant phenotypes and high ß-III tubulin expression. Since these resistance mechanisms are common in triple-negative breast cancer (TNBC), ixabepilone may have particular advantages in this patient population. This study evaluated the substitution of ixabepilone for paclitaxel following doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of early-stage TNBC. METHODS: Patients with operable TNBC were eligible following definitive breast surgery. Patients were randomized (1:1) to receive four cycles of AC followed by either four cycles (12 weeks) of ixabepilone or 12 weekly doses of paclitaxel. RESULTS: 614 patients were randomized: 306 to AC/ixabepilone and 308 to AC/paclitaxel. At a median follow-up of 48 months, 59 patients had relapsed (AC/ixabepilone, 29; AC/paclitaxel, 30). The median time from diagnosis to relapse was 20.8 months. The 5-year disease-free survival (DFS) rates of the two groups were similar [HR 0.92; ixabepilone 87.1% (95% CI 82.6-90.5) vs. paclitaxel 84.7% (95% CI 79.7-88.6)]. The estimated 5-year overall survival (OS) rates were also similar [HR 1.1; ixabepilone 89.7% (95% CI 85.5-92.7) vs. paclitaxel 89.6% (95% CI 85.0-92.9)]. Peripheral neuropathy was the most common grade 3/4 event. Dose reductions and treatment discontinuations occurred more frequently during paclitaxel treatment. CONCLUSIONS: Treatment with AC/ixabepilone provided similar DFS and OS in patients with operable TNBC when compared to treatment with AC/paclitaxel. The two regimens had similar toxicity, although treatment discontinuation, dose modifications, and overall peripheral neuropathy were more frequent with AC/paclitaxel. TRIAL REGISTRATION: Clinical Trials.gov Identifier, NCT00789581.


Asunto(s)
Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Epotilonas/administración & dosificación , Paclitaxel/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Doxorrubicina/efectos adversos , Esquema de Medicación , Epotilonas/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/efectos adversos , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/patología , Adulto Joven
3.
Breast Cancer Res ; 17: 41, 2015 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-25886996

RESUMEN

INTRODUCTION: Accurate assessment of HER2 status is critical in determining appropriate therapy for breast cancer patients but the best HER2 testing methodology has yet to be defined. In this study, we compared quantitative HER2 expression by the HERmark™ Breast Cancer Assay (HERmark) with routine HER2 testing by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and correlated HER2 results with overall survival (OS) of breast cancer patients in a multicenter Collaborative Biomarker Study (CBS). METHODS: Two hundred and thirty-two formalin-fixed, paraffin-embedded breast cancer tissues and local laboratory HER2 testing results were provided by 11 CBS sites. HERmark assay and central laboratory HER2 IHC retesting were retrospectively performed in a blinded fashion. HER2 results by all testing methods were obtained in 192 cases. RESULTS: HERmark yielded a continuum of total HER2 expression (H2T) ranging from 0.3 to 403 RF/mm2 (approximately 3 logs). The distribution of H2T levels correlated significantly (P<0.0001) with all routine HER2 testing results. The concordance of positive and negative values (equivocal cases excluded) between HERmark and routine HER2 testing was 84% for local IHC, 96% for central IHC, 85% for local FISH, and 84% for local HER2 status. OS analysis revealed a significant correlation of shorter OS with HER2 positivity by local IHC (HR=2.6, P=0.016), central IHC (HR=3.2, P=0.015), and HERmark (HR=5.1, P<0.0001) in this cohort of patients most of whom received no HER2-targeted therapy. The OS curve of discordant low (HER2 positive but H2T low, 10% of all cases) was aligned with concordant negative (HER2 negative and H2T low, HR=1.9, P=0.444), but showed a significantly longer OS than concordant positive (HER2 positive and H2T high, HR=0.31, P=0.024). Conversely, the OS curve of discordant high (HER2 negative but H2T high, 9% of all cases) was aligned with concordant positive (HR=0.41, P=0.105), but showed a significantly shorter OS than concordant negative (HR=41, P<0.0001). CONCLUSIONS: Quantitative HER2 measurement by HERmark is highly sensitive, accurately quantifies HER2 protein expression and correlates well with routine HER2 testing. When HERmark and local HER2 results were discordant, HERmark more accurately predicted overall survival.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Inmunohistoquímica , Hibridación Fluorescente in Situ , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica/métodos , Hibridación Fluorescente in Situ/métodos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Carga Tumoral , Adulto Joven
4.
Breast Cancer Res Treat ; 154(1): 89-97, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26456573

RESUMEN

Amplified PI3K/Akt/mTOR signaling is common in metastatic breast cancer (MBC). The mTOR inhibitor everolimus improves progression-free survival (PFS) when added to steroidal aromatase inhibitor therapy. This randomized phase II trial compares the efficacy of paclitaxel/bevacizumab/everolimus and paclitaxel/bevacizumab/placebo as first-line treatment for MBC. Patients with untreated HER2-negative MBC were randomized (1:1) to receive 28-day cycles of paclitaxel 90 mg/m(2) IV (days 1, 8, and 15) and bevacizumab 10 mg/kg IV (days 1, 15) with either everolimus 10 mg (Arm 1) or placebo (Arm 2) daily. Treatment continued (evaluation every 8 weeks) until progression or unacceptable toxicity. Treatment of 110 patients allowed detection of an improvement in median PFS from 11 to 16 months (70 % power, α = 0.10). Between August 2009 and June 2011, 113 patients (median age 58 years; 88 % ER or PR positive) were randomized (Arm 1, 56; Arm 2, 57). Patients in both arms received a median of six treatment cycles. Median PFS (95 % CI) was 9.1 months (6.8-18.8) for Arm 1, and 7.1 months (5.6-10.8) for Arm 2 (p = 0.89). Comparisons of other efficacy endpoints were also similar in the two treatment arms. Patients receiving everolimus had more anemia, stomatitis, diarrhea, rash, and arthralgia/myalgia, although the overall incidence of severe (grade 3/4) toxicity was similar. The addition of everolimus did not improve the efficacy of weekly paclitaxel/bevacizumab as first-line treatment for patients with HER2-negative MBC. These results contrast with the demonstrated efficacy of adding everolimus to either hormonal or HER2-targeted therapy in previously treated patients.


Asunto(s)
Bevacizumab/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Everolimus/administración & dosificación , Paclitaxel/administración & dosificación , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Receptor ErbB-2/genética
5.
Ann Surg Oncol ; 22(10): 3174-83, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26215198

RESUMEN

BACKGROUND: Multiple recent reports have documented significant variability of reoperation rates after initial lumpectomy for breast cancer. To address this issue, a multidisciplinary consensus conference was convened during the American Society of Breast Surgeons 2015 annual meeting. METHODS: The conference mission statement was to "reduce the national reoperation rate in patients undergoing breast conserving surgery for cancer, without increasing mastectomy rates or adversely affecting cosmetic outcome, thereby improving value of care." The goal was to develop a toolbox of recommendations to reduce the variability of reoperation rates and improve cosmetic outcomes. Conference participants included providers from multiple disciplines involved with breast cancer care, as well as a patient representative. Updated systematic reviews of the literature and invited presentations were sent to participants in advance. After topic presentations, voting occurred for choice of tools, level of evidence, and strength of recommendation. RESULTS: The following tools were recommended with varied levels of evidence and strength of recommendation: compliance with the SSO-ASTRO Margin Guideline; needle biopsy for diagnosis before surgical excision of breast cancer; full-field digital diagnostic mammography with ultrasound as needed; use of oncoplastic techniques; image-guided lesion localization; specimen imaging for nonpalpable cancers; use of specialized techniques for intraoperative management, including excisional cavity shave biopsies and intraoperative pathology assessment; formal pre- and postoperative planning strategies; and patient-reported outcome measurement. CONCLUSIONS: A practical approach to performance improvement was used by the American Society of Breast Surgeons to create a toolbox of options to reduce lumpectomy reoperations and improve cosmetic outcomes.


Asunto(s)
Neoplasias de la Mama/cirugía , Mamoplastia , Mastectomía Segmentaria/normas , Oncología por Radiación/normas , Reoperación , Congresos como Asunto , Consenso , Femenino , Humanos , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Sociedades Médicas , Cirujanos
6.
Cancer Med ; 13(16): e70096, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39157928

RESUMEN

BACKGROUND: Sacituzumab govitecan (sacituzumab) emerged as an important agent in metastatic and locally recurrent HER2-negative breast cancer treatment. UGT1A1 polymorphisms have also been shown to predict sacituzumab toxicity. METHODS: In this retrospective study, we sought to evaluate the associations between UGT1A1 status, toxicity, and therapeutic outcomes in sacituzumab recipients with advanced breast cancer who underwent genotype testing for UGT1A1 alleles (N = 68). RESULTS: We found 17 (25%) of our patients to be homozygous for UGT1A1*28 and 24 (35.3%) were heterozygous. Of seven African American patients with triple-negative breast cancer, five were homozygous for UGT1A1*28 and two were heterozygous. Patients with a homozygous UGT1A1*28 genotype were significantly more likely to have treatment terminated because of adverse effects. However, the polymorphism was not associated with treatment discontinuation because of disease progression. CONCLUSION: This retrospective, real-world analysis suggests potential clinical utility in UGT1A1 testing for patients receiving sacituzumab, but future trials are needed to confirm the association between genotypes and treatment outcomes.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama , Camptotecina , Progresión de la Enfermedad , Glucuronosiltransferasa , Humanos , Femenino , Glucuronosiltransferasa/genética , Persona de Mediana Edad , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/efectos adversos , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Anciano , Polimorfismo Genético , Genotipo , Inmunoconjugados
7.
JAMA Health Forum ; 5(6): e241388, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38848090

RESUMEN

Importance: The five 1997 Office of Management and Budget races in the US include American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, and White, with Hispanic ethnicity. Despite the Affordable Care Act mandating Office of Management and Budget-based collecting and reporting standards, race and ethnicity publishing in medical journals is inconsistent, despite being necessary to achieve health equity. Objective: To quantify race and ethnicity reporting rates and calculate representation quotients (RQs) in published oncology clinical trials. Evidence Review: In this systematic review, PubMed and Embase were queried for phase 2/3 clinical trials of the 6 most common noncutaneous solid cancers, published between January 1, 2012, and December 31, 2022, in 4 high-impact journals. Trial characteristics were recorded. The RQs for each race and ethnicity were calculated by dividing the percent of representation in each clinical trial publication by the percent of year-matched, site-specific incident cancers in the US, compared with Kruskal-Wallis tests with Bonferroni correction (BC). Reporting was compared between journal publications and ClinicalTrials.gov. Findings: Among 1202 publications evaluated, 364 met inclusion criteria: 16 JAMA, 241 Journal of Clinical Oncology, 19 Lancet, and 88 New England Journal of Medicine. Publications included 268 209 patients (171 132 women [64%]), with a median of 356 (IQR, 131-800) patients per publication. Reported race and ethnicity included American Indian or Alaska Native in 52 (14%) publications, Asian in 196 (54%), Black or African American in 215 (59%), Hispanic in 67 (18%), Native Hawaiian or Other Pacific Islander in 28 (8%), and White in 254 (70%). Median RQ varied across race (P < .001 BC), with 1.04 (IQR, 0.09-4.77) for Asian, 0.98 (IQR, 0.86-1.06) for White, 0.42 (IQR, 0.12-0.75) for Black or African American, and 0.00 (IQR, 0.00-0.00) for both American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander patients. Sensitivity analyses showed similar findings on subset analysis for US-only clinical trials. There was significantly less race and ethnicity reporting in the clinical trial publications compared with ClinicalTrials.gov documentation for American Indian or Alaska Native (14% vs 45%; P < .001 per McNemar χ2 test with continuity correction [MC]) and Native Hawaiian or Other Pacific Islander (8% vs 43%; P < .001 MC). Conclusions and Relevance: While most phase 2/3 oncology clinical trials published in high-impact journals report race and ethnicity, most did not report American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander racial categories. Our findings support a call to action for consistent journal policies and transparent race and ethnicity reporting, in alignment with Affordable Care Act-concordant race and ethnicity federal reporting requirements.


Asunto(s)
Grupos Raciales , Humanos , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Ensayos Clínicos Fase III como Asunto , Etnicidad/estadística & datos numéricos , Neoplasias/etnología , Neoplasias/terapia , Grupos Raciales/estadística & datos numéricos , Estados Unidos , Asiático , Indio Americano o Nativo de Alaska , Negro o Afroamericano , Nativos de Hawái y Otras Islas del Pacífico , Blanco , Hispánicos o Latinos
8.
Breast Cancer Res Treat ; 137(2): 457-64, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23224144

RESUMEN

Lapatinib, an oral, reversible inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) tyrosine kinase, has proven antitumor activity in HER2-positive metastatic breast cancer (MBC). Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. This was an open-label, single-arm, multicenter, Phase II study to evaluate the efficacy and safety of nab-paclitaxel plus lapatinib in women with HER2 over-expressing MBC who had received no more than one prior chemotherapeutic regimen. The primary efficacy endpoint was the overall response rate (ORR). This was defined as the percentage of patients having either a complete response (CR) or partial response (PR). Secondary efficacy endpoints included progression-free survival (PFS), overall survival, duration of response (DoR), time to response (TTR), and time to progression (TTP). Investigator-assessed ORR was 53 % (n = 32, 95 % confidence interval (CI): 40.7-66.0) with the majority of patient responses demonstrating a PR (47 %). Four (7 %) patient responses demonstrated a CR, and ten (17 %) a stable disease. The median Kaplan-Meier estimate of investigator-assessed PFS, DoR, TTR, and TTP was 39.7 weeks (95 % CI 34.1-63.9), 48.7 weeks (95 % CI 31.7-57.1), 7.8 weeks (95 % CI 7.4-8.1), and 41 weeks (95 % CI 39.1-64.6), respectively. Lapatinib 1,000 mg with nab-paclitaxel 100 mg/m(2) IV is feasible with manageable and predictable toxicity and an ORR of 53 % comparing favorably with other HER2-based combinations in this setting.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Albúminas/administración & dosificación , Albúminas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/mortalidad , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Femenino , Humanos , Lapatinib , Persona de Mediana Edad , Náusea/inducido químicamente , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Quinazolinas/administración & dosificación , Quinazolinas/efectos adversos , Resultado del Tratamiento
9.
J Urol ; 189(1 Suppl): S51-7; discussion S57-8, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23234632

RESUMEN

PURPOSE: Patients with bone metastases have high rates of RANKL driven bone resorption and an increased risk of skeletal morbidity. Osteoclast mediated bone resorption can be assessed by measuring urine N-telopeptide and can be inhibited by denosumab, a fully human antibody against RANKL. MATERIALS AND METHODS: Eligible patients (111) had bone metastases from prostate cancer, other solid tumors or multiple myeloma, 1 or more bone lesions and urine N-telopeptide greater than 50 nM bone collagen equivalents per mM creatinine (urine N-telopeptide greater than 50) despite the use of intravenous bisphosphonates. Patients were stratified by cancer type and screening urine N-telopeptide, and randomized to continue intravenous bisphosphonates every 4 weeks or receive 180 mg subcutaneous denosumab every 4 weeks or 180 mg every 12 weeks. The primary end point was the proportion of patients with urine N-telopeptide less than 50 at week 13. We report the efficacy results for the subset of patients with prostate cancer. RESULTS: Patients with prostate cancer represented 45% (50 of 111) of the study population. At week 13, 22 of 32 (69%) patients in the denosumab arms had urine N-telopeptide less than 50 vs 3 of 16 (19%) in the intravenous bisphosphonates cohort. At week 25, 22 of 32 (69%) denosumab treated patients continued to have urine N-telopeptide less than 50 vs 5 of 16 (31%) treated with intravenous bisphosphonates. Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to denosumab, was reported in 1 patient. CONCLUSIONS: In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/orina , Colágeno Tipo I/orina , Difosfonatos/uso terapéutico , Péptidos/orina , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/orina , Anciano , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias Óseas/secundario , Denosumab , Difosfonatos/administración & dosificación , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología
10.
Cancer ; 118(19): 4877-83, 2012 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-22354845

RESUMEN

BACKGROUND: An observational prospective nonblinded clinical trial was performed to determine the effect of a drug-induced apoptosis assay results on treatments planned by oncologists. METHODS: Purified cancer cells from patient biopsies were placed into the MiCK (Microculture Kinetic) assay, a short-term culture, which determined the effects of single drugs or combinations of drugs on tumor cell apoptosis. An oncologist received the assay results before finalizing the treatment plan. Use of the MiCK assay was evaluated and correlated with patient outcomes. RESULTS: Forty-four patients with successful MiCK assays from breast cancer (n = 16), nonsmall cell lung cancer (n = 6), non-Hodgkin lymphoma (n = 4), and others were evaluated. Four patients received adjuvant chemotherapy after MiCK, and 40 received palliative chemotherapy with a median line of therapy of 2. Oncologists used the MiCK assay to determine chemotherapy (users) in 28 (64%) and did not (nonusers) in 16 patients (36%). In users receiving palliative chemotherapy, complete plus partial response rate was 44%, compared with 6.7% in nonusers (P < .02). The median overall survival was 10.1 months in users versus 4.1 months in nonusers (P = .02). Relapse-free interval was 8.6 months in users versus 4.0 months in nonusers (P < .01). CONCLUSIONS: MiCK assay results are frequently used by oncologists. Outcomes appear to be statistically superior when oncologists use chemotherapy based on MiCK assay results compared with when they do not use the assay results. When available to oncologists, MiCK assay results help to determine patient treatment plans.


Asunto(s)
Antineoplásicos , Apoptosis/efectos de los fármacos , Conducta de Elección , Prescripciones de Medicamentos/estadística & datos numéricos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias/tratamiento farmacológico , Médicos/estadística & datos numéricos , Anciano , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Toma de Decisiones , Supervivencia sin Enfermedad , Prescripciones de Medicamentos/normas , Ensayos de Selección de Medicamentos Antitumorales/métodos , Ensayos de Selección de Medicamentos Antitumorales/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Estados Unidos
11.
Cancer ; 118(5): 1192-201, 2012 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-21987386

RESUMEN

BACKGROUND: Postmenopausal breast cancer (BC) patients receiving adjuvant aromatase inhibitor therapy are at risk of progressive bone loss and fractures. Zoledronic acid inhibits osteoclastic bone resorption, is effective in maintaining bone health, and may therefore be beneficial in this setting. METHODS: Overall, 602 postmenopausal women with early, hormone receptor-positive BC receiving adjuvant letrozole were randomized (301 each group) to receive upfront or delayed-start zoledronic acid (4 mg intravenously every 6 months) for 5 years. The primary endpoint was the change in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary endpoints included changes in LS BMD, total hip BMD, and bone turnover markers at 2, 3, and 5 years; fracture incidence at 3 years; and time to disease recurrence. RESULTS: At month 61, the adjusted mean difference in LS and total hip BMDs between the upfront and delayed groups was 8.9% and 6.7%, respectively (P < .0001, for both). Approximately 25% of delayed patients received zoledronic acid by month 61. Only 1 patient experienced grade 4 renal dysfunction; no confirmed cases of osteonecrosis of the jaw were reported. Fracture rates (upfront, 28 [9.3%]; delayed, 33 [11%]; P = .3803) and Kaplan-Meier disease recurrence rates (upfront, 9.8 [95% confidence interval (CI), 6.0-10.3]; delayed, 10.5 [95% CI, 6.6-14.4]; P = .6283) were similar at month 61. CONCLUSIONS: Upfront zoledronic acid seems to be the preferred treatment strategy versus delayed administration, as it significantly and progressively increases BMD in postmenopausal women with early BC receiving letrozole for 5 years, and long-term coadministration of letrozole and zoledronic acid is well tolerated.


Asunto(s)
Huesos/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Difosfonatos/uso terapéutico , Imidazoles/uso terapéutico , Nitrilos/uso terapéutico , Osteoporosis Posmenopáusica/prevención & control , Triazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/uso terapéutico , Huesos/patología , Neoplasias de la Mama/complicaciones , Carcinoma/complicaciones , Quimioterapia Adyuvante , Difosfonatos/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Imidazoles/administración & dosificación , Letrozol , Persona de Mediana Edad , Nitrilos/administración & dosificación , Nitrilos/efectos adversos , Tamaño de los Órganos/efectos de los fármacos , Osteoporosis Posmenopáusica/inducido químicamente , Osteoporosis Posmenopáusica/complicaciones , Osteoporosis Posmenopáusica/epidemiología , Posmenopausia/efectos de los fármacos , Triazoles/administración & dosificación , Triazoles/efectos adversos , Ácido Zoledrónico
12.
Qual Life Res ; 21(7): 1255-66, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21987032

RESUMEN

PURPOSE: To develop a patient-reported outcome instrument for measuring anemia symptoms and their impact in patients with chemotherapy-induced anemia (CIA). METHODS: Qualitative research was conducted using six focus groups and 24 interviews with 46 CIA patients, eight interviews in patients receiving chemotherapy with no CIA history and two interviews in patients successfully treated for CIA. Atlas.ti 5.0 was used to organize key concepts. Cognitive interviews with 16 CIA patients and assessment of relevance of each item to CIA by 10 clinicians were also conducted to evaluate content validity. RESULTS: Most CIA patients were white (76%) and female (83%), and the average age was 60 years. The most common cancer types were breast cancer (54%) and lung cancer (17%). Tiredness was the most prevalent symptom and rated as the most important by 83% of CIA patients; weakness, shortness of breath, lightheadedness, and dizziness were ranked next in importance. The final anemia impact measure (AIM) contains: (1) daily CIA symptom diary (9 items), and (2) impact of CIA-related tiredness (29 items covering daily living activities, social activities, cognitive function, and emotions). Cognitive interviews found that the AIM was relevant and easy to understand. CONCLUSIONS: The AIM assesses important patient-perceived CIA symptoms and their impact and was developed using extensive patient qualitative data.


Asunto(s)
Anemia/inducido químicamente , Anemia/fisiopatología , Calidad de Vida , Actividades Cotidianas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Grupos Focales , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Psicometría/instrumentación
13.
JAMA Netw Open ; 5(5): e2214514, 2022 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-35639380

RESUMEN

Importance: To date, oncologist and model prognostic performance have been assessed independently and mostly retrospectively; however, how model prognostic performance compares with oncologist prognostic performance prospectively remains unknown. Objective: To compare oncologist performance with a model in predicting 3-month mortality for patients with metastatic solid tumors in an outpatient setting. Design, Setting, and Participants: This prognostic study evaluated prospective predictions for a cohort of patients with metastatic solid tumors seen in outpatient oncology clinics at a National Cancer Institute-designated cancer center and associated satellites between December 6, 2019, and August 6, 2021. Oncologists (57 physicians and 17 advanced practice clinicians) answered a 3-month surprise question (3MSQ) within clinical pathways. A model was trained with electronic health record data from January 1, 2013, to April 24, 2019, to identify patients at high risk of 3-month mortality and deployed silently in October 2019. Analysis was limited to oncologist prognostications with a model prediction within the preceding 30 days. Exposures: Three-month surprise question and gradient-boosting binary classifier. Main Outcomes and Measures: The primary outcome was performance comparison between oncologists and the model to predict 3-month mortality. The primary performance metric was the positive predictive value (PPV) at the sensitivity achieved by the medical oncologists with their 3MSQ answers. Results: A total of 74 oncologists answered 3099 3MSQs for 2041 patients with advanced cancer (median age, 62.6 [range, 18-96] years; 1271 women [62.3%]). In this cohort with a 15% prevalence of 3-month mortality and 30% sensitivity for both oncologists and the model, the PPV of oncologists was 34.8% (95% CI, 30.1%-39.5%) and the PPV of the model was 60.0% (95% CI, 53.6%-66.3%). Area under the receiver operating characteristic curve for the model was 81.2% (95% CI, 79.1%-83.3%). The model significantly outperformed the oncologists in short-term mortality. Conclusions and Relevance: In this prognostic study, the model outperformed oncologists overall and within the breast and gastrointestinal cancer cohorts in predicting 3-month mortality for patients with advanced cancer. These findings suggest that further studies may be useful to examine how model predictions could improve oncologists' prognostic confidence and patient-centered goal-concordant care at the end of life.


Asunto(s)
Neoplasias Primarias Secundarias , Neoplasias , Oncólogos , Femenino , Humanos , Aprendizaje Automático , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos
14.
Cancers (Basel) ; 14(13)2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35804935

RESUMEN

Cyclin-dependent kinase 4/6 inhibitors are the standard of care for hormone receptor-positive metastatic breast cancer. This retrospective study reports on genomic biomarkers of CDK 4/6i resistance utilizing genomic data acquired through routine clinical practice. Patients with HR+ MBC treated with palbociclib, ribociclib, or abemaciclib and antiestrogen therapy were identified. Patients were grouped into early (<6 months); intermediate (6−24 months for 0−1 lines; 6−9 months for ≥2 lines); or late progressors (>24 months for 0−1 lines; >9 months PFS for ≥2 lines). NGS and RNA sequencing data were analyzed in association with PFS, and survival analysis was stratified by prior lines of chemotherapy. A total of 795 patients with HR+ MBC treated with CDK 4/6i were identified. Of these, 144 (18%) patients had genomic data and 29 (3.6%) had RNA data. Among the 109 patients who received CDK4/6i as 1st- or 2nd-line therapy, 17 genes showed associations with PFS (p-value ≤ 0.15 and HR ≥ 1.5 or HR < 0.5). Whole transcriptome RNAseq was analyzed for 24/109 (22%) patients with 0−1 prior lines of therapy and 56 genes associated with PFS (HR ≥ 4 or HR ≤ 0.25 and FDR ≤ 0.15). In this retrospective analysis, genomic biomarkers including FGFR1 amplification, PTEN loss, and DNA repair pathway gene mutations showed significant associations with shorter PFS for patients receiving CDK4/6 inhibitor therapy.

15.
J Clin Med ; 11(22)2022 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-36431215

RESUMEN

The complexity of cancer care requires integrated and continuous support to deliver appropriate care. An expert network with complementary expertise and the capability of multidisciplinary care is an integral part of contemporary oncology care. Appropriate infrastructure is necessary to empower this network to deliver personalized precision care to their patients. Providing decision support as cancer care becomes exponentially more complex with new diagnostic and therapeutic choices remains challenging. City of Hope has developed a Pyramidal Decision Support Framework to address these challenges, which were exacerbated by the COVID pandemic, health plan restrictions, and growing geographic site diversity. Optimizing efficient and targeted decision support backed by multidisciplinary cancer expertise can improve individual patient treatment plans to achieve improved care and survival wherever patients are treated.

16.
J Clin Med ; 10(2)2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33430334

RESUMEN

As the US transitions from volume- to value-based cancer care, many cancer centers and community groups have joined to share resources to deliver measurable, high-quality cancer care and clinical research with the associated high patient satisfaction, provider satisfaction, and practice health at optimal costs that are the hallmarks of value-based care. Multidisciplinary oncology care pathways are essential components of value-based care and their payment metrics. Oncology pathways are evidence-based, standardized but personalizable care plans to guide cancer care. Pathways have been developed and studied for the major medical, surgical, radiation, and supportive oncology disciplines to support decision-making, streamline care, and optimize outcomes. Implementing multidisciplinary oncology pathways can facilitate comprehensive care plans for each cancer patient throughout their cancer journey and across large multisite delivery systems. Outcomes from the delivered pathway-based care can then be evaluated against individual and population benchmarks. The complexity of adoption, implementation, and assessment of multidisciplinary oncology pathways, however, presents many challenges. We review the development and components of value-based cancer care and detail City of Hope's (COH) academic and community-team-based approaches for implementing multidisciplinary pathways. We also describe supportive components with available results towards enterprise-wide value-based care delivery.

17.
J Clin Med ; 9(5)2020 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-32455877

RESUMEN

Cancer is a disease associated with aging. As the US population ages, the number of older adults with cancer is projected to dramatically increase. Despite this, older adults remain vastly underrepresented in research that sets the standards for cancer treatments and, consequently, clinicians struggle with how to interpret data from clinical trials and apply them to older adults in practice. A combination of system, clinician, and patient barriers bar opportunities for trial participation for many older patients, and strategies are needed to address these barriers at multiple fronts, five of which are offered here. This review highlights the need to (1) broaden eligibility criteria, (2) measure relevant end points, (3) expand standard trial designs, (4) increase resources (e.g., institutional support, interdisciplinary care, and telehealth), and (5) develop targeted interventions (e.g., behavioral interventions to promote patient enrollment). Implementing these solutions requires a substantial investment in engaging and collaborating with community-based practices, where the majority of older patients with cancer receive their care. Multifaceted strategies are needed to ensure that older patients with cancer, across diverse healthcare settings, receive the highest-quality, evidence-based care.

18.
JCO Oncol Pract ; 16(4): 191-199, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32223701

RESUMEN

Oncologist well-being is critical to initiating and maintaining the physician-patient relationship, yet many oncologists suffer from symptoms of burnout. Burnout has been linked to poor physical and mental health, as well as increased medical errors, patient dissatisfaction, and workforce attrition. In this Call to Action article, we discuss causes of and interventions for burnout and moral distress in oncology, highlight existing interventions, and provide recommendations for addressing burnout and improving well-being at the individual and organizational levels to deliver ethical, quality cancer care.


Asunto(s)
Agotamiento Profesional , Oncólogos , Comités de Ética , Humanos , Oncología Médica , Principios Morales
19.
Nat Commun ; 11(1): 5824, 2020 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-33203854

RESUMEN

In this multicenter, open-label, randomized phase II investigator-sponsored neoadjuvant trial with funding provided by Sanofi and GlaxoSmithKline (TRIO-US B07, Clinical Trials NCT00769470), participants with early-stage HER2-positive breast cancer (N = 128) were recruited from 13 United States oncology centers throughout the Translational Research in Oncology network. Participants were randomized to receive trastuzumab (T; N = 34), lapatinib (L; N = 36), or both (TL; N = 58) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. The primary objective was to estimate the rate of pathologic complete response (pCR) at the time of surgery in each of the three arms. In the intent-to-treat population, we observed similar pCR rates between T (47%, 95% confidence interval [CI] 30-65%) and TL (52%, 95% CI 38-65%), and a lower pCR rate with L (25%, 95% CI 13-43%). In the T arm, 100% of participants completed all protocol-specified treatment prior to surgery, as compared to 69% in the L arm and 74% in the TL arm. Tumor or tumor bed tissue was collected whenever possible pre-treatment (N = 110), after one cycle of HER2-targeted therapy alone (N = 89), and at time of surgery (N = 59). Higher-level amplification of HER2 and hormone receptor (HR)-negative status were associated with a higher pCR rate. Large shifts in the tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Microambiente Tumoral/efectos de los fármacos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/cirugía , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Lapatinib/administración & dosificación , Lapatinib/uso terapéutico , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Terapia Neoadyuvante , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Trastuzumab/administración & dosificación , Trastuzumab/uso terapéutico , Resultado del Tratamiento , Microambiente Tumoral/genética
20.
J Urol ; 182(2): 509-15; discussion 515-6, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19524963

RESUMEN

PURPOSE: Patients with bone metastases have high rates of RANKL driven bone resorption and an increased risk of skeletal morbidity. Osteoclast mediated bone resorption can be assessed by measuring urine N-telopeptide and can be inhibited by denosumab, a fully human antibody against RANKL. MATERIALS AND METHODS: Eligible patients (111) had bone metastases from prostate cancer, other solid tumors or multiple myeloma, 1 or more bone lesions and urine N-telopeptide greater than 50 nM bone collagen equivalents per mM creatinine (urine N-telopeptide greater than 50) despite the use of intravenous bisphosphonates. Patients were stratified by cancer type and screening urine N-telopeptide, and randomized to continue intravenous bisphosphonates every 4 weeks or receive 180 mg subcutaneous denosumab every 4 weeks or 180 mg every 12 weeks. The primary end point was the proportion of patients with urine N-telopeptide less than 50 at week 13. We report the efficacy results for the subset of patients with prostate cancer. RESULTS: Patients with prostate cancer represented 45% (50 of 111) of the study population. At week 13, 22 of 32 (69%) patients in the denosumab arms had urine N-telopeptide less than 50 vs 3 of 16 (19%) in the intravenous bisphosphonates cohort. At week 25, 22 of 32 (69%) denosumab treated patients continued to have urine N-telopeptide less than 50 vs 5 of 16 (31%) treated with intravenous bisphosphonates. Grade 4, asymptomatic, reversible hypophosphatemia, possibly related to denosumab, was reported in 1 patient. CONCLUSIONS: In patients with prostate cancer related bone metastases and increased urine N-telopeptide despite intravenous bisphosphonate treatment, denosumab normalized urine N-telopeptide levels more frequently than ongoing intravenous bisphosphonates.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Conservadores de la Densidad Ósea/administración & dosificación , Neoplasias Óseas/secundario , Neoplasias Óseas/orina , Colágeno Tipo I/orina , Difosfonatos/administración & dosificación , Péptidos/orina , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/orina , Ligando RANK/uso terapéutico , Anciano , Anticuerpos Monoclonales Humanizados , Denosumab , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad
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