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1.
Oncologist ; 25(2): e373-e380, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32043774

RESUMEN

BACKGROUND: We previously reported the results of a prospective study of chemotherapy-induced nausea and vomiting (CINV) in a cohort of patients who received carboplatin-based chemotherapy and were selected from a nationwide registry of those scheduled for moderately (MEC) or highly emetogenic chemotherapy (HEC) by the CINV Study Group of Japan. Of 1,910 previously registered patients (HEC: 1,195; MEC: 715), 400 patients received carboplatin-based chemotherapy. The frequency of CINV was determined, and the risk factors for CINV were assessed. MATERIALS AND METHODS: CINV data were collected from 7-day diaries. Risk factors for CINV were identified using logistic regression models. RESULTS: Of 400 patients scheduled for carboplatin-based chemotherapy, 267 patients received two antiemetics (5-hydroxytryptamine-3 receptor antagonist [5-HT3 RA] and dexamethasone [DEX]), 118 patients received three antiemetics (5-HT3 RA, DEX, and neurokinin-1 receptor antagonist [NK1 RA]), and 15 were nonadherent to the treatment. In these patients, the CINV overall, acute, and delayed phase rates of complete response (CR), defined as no vomiting with no rescue medication, were 67.0%, 98.2%, and 67.5%, respectively. The rates of no nausea were 55.6%, 94.0%, and 56.1%, respectively, and those of no vomiting were 81.3%, 99.0%, and 81.8%, respectively. Older age was associated with a decreased non-CR, whereas female sex, history of pregnancy-related emesis, and dual antiemetic therapy were associated with an increased non-CR during the overall period. CONCLUSION: In a clinical practice setting, in patients who received carboplatin-based chemotherapy, adherence is quite high and appropriate antiemetic prophylaxis requires a triple antiemetic regimen including NK1 RA. IMPLICATIONS FOR PRACTICE: For patients receiving carboplatin-based chemotherapy, triple antiemetic therapy with 5-hydroxytryptamine-3 receptor antagonist, dexamethasone, and neurokinin-1 receptor antagonist should be given prophylactically regardless of risk factor status.

2.
Breast Cancer ; 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32002789

RESUMEN

Secretory breast carcinoma constitutes the majority of breast cancers in children and young people less than 20 years of age. Noninvasive examination is particularly necessary for the diagnosis of breast carcinoma in children. Herein, we report a case of secretory breast carcinoma in a 6-year-old girl with psychomotor retardation. She was referred to our outpatient clinic for evaluation of a palpable mass in her left breast. A hard mass, rather than the increase in size typical of premature thelarche, was palpated. An excision biopsy was performed. Pathological findings revealed an invasive secretory breast carcinoma. We performed a retrospective review of the preoperative findings of this case, and compared it to the pathological diagnosis. Elastography, which can be performed without deep sedation or general anesthesia and without causing pain, resulted in a stiffness score of 4; however, the distinction between benign and malignant tumors on elastography, which is important to decide the intra-operative procedures, was not sufficient according to the Japanese breast cancer society clinical guidelines. This is the first report of secretory breast carcinoma in a child with a stiffness score determined by tissue elasticity imaging. A breast mass in a child with a high stiffness score of more than 4 on elastography should be referred for invasive diagnostic procedures, such as fine needle aspiration or excisional biopsy. According to our experience, an accurate preoperative diagnosis could be possible for malignant breast tumors in children. Such parameters as stiffness score on elastography are practical, noninvasive, and objective diagnostic tools for the accurate preoperative diagnosis of breast tumors in children.

3.
Breast Cancer ; 27(1): 122-128, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31407150

RESUMEN

PURPOSE: To explore the actual status of chemotherapy-induced nausea and vomiting (CINV) through a multicenter prospective cohort study. METHODS: Patients with breast cancer treated with moderately emetogenic (MEC) or highly emetogenic (HEC) chemotherapy were eligible. A 7-day diary was provided for all patients. Acute and delayed CINV were defined as nausea and vomiting that developed ≤ 24 or > 24 h after the start of chemotherapy, respectively. The severity of nausea was evaluated with a visual analog scale (VAS). We also assessed the accuracy of estimations of CINV by medical staff. RESULTS: In total, 426 patients were included; 352 patients (82.6%) received HEC, and 74 (17.3%) received MEC. In the acute phase, 44.9% of patients receiving HEC and 5.4% receiving MEC experienced nausea, and 12.8% receiving HEC and none receiving MEC experienced vomiting. More patients experienced nausea in both groups and vomiting in MEC during the delayed phase (nausea: 59.4% in HEC and 44.6% in MEC group; vomiting: 11.1% in HEC; and 13.5% in MEC group) than during the acute phase. Estimations of CINV by medical staff were not accurate, with a kappa coefficient of 0.10 and 0.08 for acute nausea and vomiting and 0.02 and 0.01 for delayed. The VAS scores showed that in the HEC group, the degree of nausea was worst on the first day. CONCLUSIONS: The degree of nausea was worst in the acute phase, although delayed nausea was more in proportion in HEC. Estimation by medical staff is not accurate.

5.
Gan To Kagaku Ryoho ; 46(11): 1683-1685, 2019 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-31748472

RESUMEN

For anti-emetic therapy, the first guideline was published 2010, following second version was open for public in 2015. The latest guideline for anti-emetic therapy in Japan, version 2.2 was disclosed on web site of Japan Society of Clinical Oncology. The point of new version were included 3 points which were a new categorization of moderately emetic chemotherapy, improvement of olanzapine for anti-emetic drug, and steroid spearing for MEC.


Asunto(s)
Antieméticos/uso terapéutico , Guías de Práctica Clínica como Asunto , Antineoplásicos , Humanos , Japón , Náusea , Vómitos
6.
Oncologist ; 2019 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-31636146

RESUMEN

BACKGROUND: We previously reported the results of a prospective study of chemotherapy-induced nausea and vomiting (CINV) in a cohort of patients who received carboplatin-based chemotherapy and were selected from a nationwide registry of those scheduled for moderately (MEC) or highly emetogenic chemotherapy (HEC) by the CINV Study Group of Japan. Of 1,910 previously registered patients (HEC: 1,195; MEC: 715), 400 patients received carboplatin-based chemotherapy. The frequency of CINV was determined, and the risk factors for CINV were assessed. MATERIALS AND METHODS: CINV data were collected from 7-day diaries. Risk factors for CINV were identified using logistic regression models. RESULTS: Of 400 patients scheduled for carboplatin-based chemotherapy, 267 patients received two antiemetics (5-hydroxytryptamine-3 receptor antagonist [5-HT3 RA] and dexamethasone [DEX]), 118 patients received three antiemetics (5-HT3 RA, DEX, and neurokinin-1 receptor antagonist [NK1 RA]), and 15 were nonadherent to the treatment. In these patients, the CINV overall, acute, and delayed phase rates of complete response (CR), defined as no vomiting with no rescue medication, were 67.0%, 98.2%, and 67.5%, respectively. The rates of no nausea were 55.6%, 94.0%, and 56.1%, respectively, and those of no vomiting were 81.3%, 99.0%, and 81.8%, respectively. Older age was associated with a decreased non-CR, whereas female sex, history of pregnancy-related emesis, and dual antiemetic therapy were associated with an increased non-CR during the overall period. CONCLUSION: In a clinical practice setting, in patients who received carboplatin-based chemotherapy, adherence is quite high and appropriate antiemetic prophylaxis requires a triple antiemetic regimen including NK1 RA. IMPLICATIONS FOR PRACTICE: For patients receiving carboplatin-based chemotherapy, triple antiemetic therapy with 5-hydroxytryptamine-3 receptor antagonist, dexamethasone, and neurokinin-1 receptor antagonist should be given prophylactically regardless of risk factor status.

7.
Cancer ; 125(22): 4076-4083, 2019 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-31381152

RESUMEN

BACKGROUND: The current randomized, double-blind, phase 2 study assessed the efficacy and safety profile of a single intravenous administration of fosnetupitant, a neurokinin 1 receptor antagonist prodrug, for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving cisplatin-based chemotherapy. METHODS: Patients scheduled to receive cisplatin (at a dose of ≥70 mg/m2 )-based regimens were randomly assigned to receive fosnetupitant at a dose of 81 mg or 235 mg or placebo in combination with palonosetron at a dose of 0.75 mg and dexamethasone. The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase (0-120 hours). The overall CR rate was compared between each dose of fosnetupitant and the placebo group adjusting for the stratification factors of sex and age class (age <55 years vs age ≥55 years). Safety was assessed, with special attention given to events that potentially were suggestive of infusion site reactions. RESULTS: A total of 594 patients were randomized. Of these, 194 patients, 195 patients, and 195 patients, respectively, in the placebo and fosnetupitant 81-mg and 235-mg dose groups were evaluable for efficacy. The overall CR rate was 54.7% for the placebo group, 63.8% for the fosnetupitant 81-mg dose group (adjusted difference, 9.1%; 95% CI, -0.4% to 18.6% [P = .061]), and 76.8% for the fosnetupitant 235-mg dose group (adjusted difference, 22.0%; 97.5% CI, 11.7% to 32.3% [P < .001]). Safety profiles were comparable between the 3 groups. The incidence of infusion site reactions related to fosnetupitant was ≤1% in each dose group. CONCLUSIONS: Fosnetupitant at a dose of 235 mg provided superior prevention of chemotherapy-induced nausea and vomiting among patients receiving cisplatin-based chemotherapy compared with the control group, and with a satisfactory safety profile.

8.
Med Oncol ; 36(6): 54, 2019 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-31062258

RESUMEN

One-step nucleic acid amplification (OSNA) for CK19 mRNA is an intraoperative diagnostic procedure for detection of lymph node metastasis. Automated Gene Amplification Detector RD-200 and the LYNOAMP CK19 gene amplification reagent as components of a new OSNA system have been developed. As an improvement over a conventional system, the new system can analyze 14 samples per run, evaluate two lymph nodes in ~ 17 min, and reduce inhibition of reactions. This study was aimed at evaluating clinical performance of the new system by comparing it with performance of histopathological analysis and a conventional OSNA system. A total of 150 lymph nodes in 63 breast cancer patients (T1-3) who underwent sentinel lymph node biopsy or axillary lymph node dissection were examined intraoperatively with the new OSNA system, the conventional system, and histopathological analysis. In comparison with histopathological analysis, sensitivity, specificity, and concordance rate of the new system were 93.9, 98.8, and 96.7%, respectively. In comparison with the conventional system, similar corresponding values were obtained: 96.9, 98.8, and 98.0%, respectively. The results show that clinical performance of the new OSNA system is equivalent to that of histopathological diagnosis and the conventional OSNA system. The new system is superior to the conventional one because of processing of a greater number of samples, shorter testing time, and the absence of inhibited reactions.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Queratina-19/genética , Ganglios Linfáticos/patología , Técnicas de Amplificación de Ácido Nucleico/métodos , Adulto , Anciano , Anciano de 80 o más Años , Axila , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Periodo Intraoperatorio , Metástasis Linfática , Persona de Mediana Edad , ARN Mensajero/metabolismo , Sensibilidad y Especificidad
9.
Br J Cancer ; 120(5): 475-480, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30745582

RESUMEN

BACKGROUND: NK105 is a novel nanoparticle drug delivery formulation that encapsulates paclitaxel (PTX) in polymeric micelles. We conducted an open-label phase III non-inferiority trial to compare the efficacy and safety of NK105 and PTX in metastatic or recurrent breast cancer. METHODS: Patients were randomly assigned in a 1:1 ratio to receive either NK105 (65 mg/m2) or PTX (80 mg/m2) on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS), with a non-inferiority margin of 1.215. RESULTS: A total of 436 patients were randomised and 211 patients in each group were included in the efficacy analysis. The median PFS was 8.4 and 8.5 months for NK105 and PTX, respectively (adjusted hazard ratio: 1.255; 95% confidence interval: 0.989-1.592). The median overall survival and overall response rates were 31.2 vs. 36.2 months and 31.6% vs. 39.0%, respectively. The two groups exhibited similar safety profiles. The incidence of peripheral sensory neuropathy (PSN) was 1.4% vs. 7.5% (≥Grade 3) for NK105 and PTX, respectively. The patient-reported outcomes of PSN were significantly favourable for NK105 (P < 0.0001). CONCLUSIONS: The primary endpoint was not met, but NK105 had a better PSN toxicity profile than PTX. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT01644890.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/análogos & derivados , Paclitaxel/uso terapéutico , Adenocarcinoma/secundario , Adulto , Anciano , Neoplasias de la Mama/patología , Estudios de Equivalencia como Asunto , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales
10.
Jpn J Clin Oncol ; 49(2): 121-129, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30576544

RESUMEN

Objective: Netupitant is a novel, selective neurokinin-1 receptor antagonist used for prevention of chemotherapy-induced nausea and vomiting, a distressing side effect of chemotherapy. This double-blind, randomized, Phase II study investigated the dose-response of oral netupitant in Japanese patients receiving highly emetogenic chemotherapy. Methods: Chemotherapy-naïve patients were randomized (1:1:1) to a single oral netupitant 30-, 100- or 300-mg dose before chemotherapy initiation. Patients received concomitant palonosetron (0.75 mg intravenously [i.v.] Day 1) and dexamethasone (9.9 mg i.v. Day 1, 8 mg orally Days 2-4). Results: Overall, 402 patients (30 mg: 134; 100 mg: 135; 300 mg: 133) were treated and evaluable for efficacy and safety. The primary endpoint of overall (0-120 h after chemotherapy administration) complete response (CR) rate (no emesis, no rescue medication) was 64.2%, 60.0% and 54.9% in the 30-, 100- and 300-mg arms, respectively, without statistical significance for dose-response. The safety profile of netupitant was comparable in the three arms. The plasma concentrations of netupitant and its metabolites increased with the dose increase from 30 mg to 300 mg. Conclusions: No dose-response relationship of netupitant in terms of overall CR rate was observed in this study. Netupitant was well tolerated at all doses without clinically harmful safety signals observed. Clinical trial registration: JapicCTI-142 483.


Asunto(s)
Antineoplásicos/efectos adversos , Eméticos/efectos adversos , Náusea/tratamiento farmacológico , Palonosetrón/administración & dosificación , Palonosetrón/uso terapéutico , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Vómitos/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Aminas , Antieméticos/administración & dosificación , Antieméticos/uso terapéutico , Método Doble Ciego , Determinación de Punto Final , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Náusea/sangre , Náusea/inducido químicamente , Náusea/prevención & control , Palonosetrón/sangre , Palonosetrón/farmacocinética , Piridinas/sangre , Piridinas/farmacocinética , Resultado del Tratamiento , Vómitos/sangre , Vómitos/inducido químicamente , Vómitos/prevención & control
11.
Anticancer Res ; 39(1): 225-230, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30591462

RESUMEN

BACKGROUND/AIM: The incidence of delayed chemotherapy-induced nausea and vomiting (CINV), especially nausea, in gynecologic cancer patients who receive paclitaxel and carboplatin (TC) chemotherapy is unclear. We assessed risk factors for delayed CINV in these patients, and examined whether it was controlled with combination antiemetic therapy. MATERIALS AND METHODS: Data were pooled from two prospective studies, and compared between the two antiemetic prophylaxis groups using inverse probability of treatment weighted (IPTW) analysis. RESULTS: Among the 182 evaluable patients (mean age: 56.2 years), three antiemetics gave better overall control than two for delayed nausea (42.9% vs. 57.4%,) and vomiting (13.8% vs. 34.5%). Risk factor for delayed nausea was age [odds ratio (OR)=0.953; p=0.0898[and use of two antiemetics (vs. three antiemetics) for delayed vomiting (OR=0.304; p=0.0732). CONCLUSION: A combination of three antiemetics controls delayed CINV among patients who undergo TC chemotherapy. Identification of risk factors can facilitate personalized treatments.


Asunto(s)
Antieméticos/administración & dosificación , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Náusea/tratamiento farmacológico , Vómitos/tratamiento farmacológico , Anciano , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Terapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Femenino , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/patología , Humanos , Quimioterapia de Inducción/efectos adversos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/patología , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Estudios Prospectivos , Vómitos/inducido químicamente , Vómitos/patología
13.
Breast Cancer Res ; 20(1): 107, 2018 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-30185224

RESUMEN

After the publication of this article [1], we noticed that in Fig. 2, the survival curve images (C and D, lower panel) were incorrect. The corrected Fig. 2 is presented below. The correction does not affect in any our results and conclusions.

14.
J Contemp Brachytherapy ; 10(3): 274-278, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30038649

RESUMEN

We initiated the first multi-institutional prospective study of accelerated partial breast irradiation for early breast cancer in Japan. Our early clinical results showed that the treatment methods were technically reproducible between institutions and showed excellent disease control at a median follow-up of 26 months in our previous report. At present, total 46 patients from six institutions underwent the treatment regimen from October 2009 to December 2011, and the median follow-up time was 60 months (range, 57-67 months). In 46 patients, we experienced one patient who had rib fracture as a late complication. The dose-volume histogram (DVH) result of this patient was analyzed. The D0.01cc, D0.1cc, and D1cc values of the patient were 913, 817, and 664 cGy per fraction, respectively. These values were the highest values in 46 patients. The average D0.01cc, D0.1cc, and D1cc values of the other 45 patients were 546, 500, and 419, respectively, cGy per fraction. From this result, DVH values showing high-dose irradiated volume (D0.01cc, D0.1cc, and D1cc) seem to be a good predictive factor of rib fracture for accelerated partial breast irradiation. However, further investigation is necessary because of the small number of patients investigated.

15.
Breast Cancer Res ; 20(1): 78, 2018 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-30053906

RESUMEN

BACKGROUND: Hypoxia is a key driver of cancer progression. We evaluated the prognostic impact of 18F-fluoromisonidazole (FMISO) prior to treatment in patients with breast cancer. METHODS: Forty-four patients with stage II/III primary breast cancer underwent positron emission tomography/computed with 18F-fluorodeoxyglucose (FDG-PET/CT) and FMISO. After measurement by FDG-PET/CT, the tissue-to-blood ratio (TBR) was obtained using FMISO-PET/CT. FMISO-TBR was compared for correlation with clinicopathological factors, disease-free survival (DFS), and overall survival (OS). Multiplex cytokines were analyzed for the correlation of FMISO-TBR. RESULTS: Tumors with higher nuclear grade and negativities of estrogen receptor (ER) and progesterone receptor had significantly higher FMISO-TBR than other tumors. Kaplan-Meier survival curves showed that patients with a higher FMISO-TBR (cutoff, 1.48) had a poorer prognosis of DFS (p = 0.0007) and OS (p = 0.04) than those with a lower FMISO-TBR. Multivariate analysis indicated that higher FMISO-TBR and ER negativity were independent predictors of shorter DFS (p = 0.01 and 0.03). Higher FMISO-TBR was associated with higher plasma levels of angiogenic hypoxic markers such as vascular endothelial growth factor, transforming growth factor-α, and interleukin 8. CONCLUSIONS: FMISO-PET/CT is useful for assessing the prognosis of patients with breast cancer, but it should be stratified by ER status. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000006802 . Registered on 1 December 2011.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Misonidazol/análogos & derivados , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos/administración & dosificación , Adulto , Anciano , Mama/diagnóstico por imagen , Mama/patología , Neoplasias de la Mama/mortalidad , Hipoxia de la Célula , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Humanos , Persona de Mediana Edad , Misonidazol/administración & dosificación , Pronóstico , Receptores Estrogénicos/metabolismo
16.
Breast ; 40: 67-75, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29698927

RESUMEN

BACKGROUND: For human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies. PATIENTS AND METHODS: Women with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA. RESULTS: Eighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55-1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26-1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX. CONCLUSION: In women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX. TRIAL REGISTRATION NUMBER: UMIN000005219.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Capecitabina/administración & dosificación , Quinazolinas/administración & dosificación , Receptor ErbB-2 , Trastuzumab/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Fosfatidilinositol 3-Quinasa Clase I/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Lapatinib , Persona de Mediana Edad , Mutación , Receptor ErbB-2/metabolismo , Taxoides/uso terapéutico , Resultado del Tratamiento
17.
Future Oncol ; 14(19): 1909-1919, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29482364

RESUMEN

Trastuzumab is an anti-HER2 monoclonal antibody indicated for the treatment of HER2-overexpressing breast and gastric cancers. Despite its clinical efficacy, access to the biological drug can be limited due to its relatively high price, especially in low-income countries. CT-P6 (Herzuma®) is a biosimilar candidate of originator or 'reference' trastuzumab, which may offer an alternative, more cost-effective treatment option. This article reviews the unmet needs of patients eligible to receive reference trastuzumab and the potential place of a trastuzumab biosimilar within the market. The review also summarizes the available clinical evidence supporting the biosimilarity of CT-P6 and reference trastuzumab with respect to pharmacokinetics, efficacy, safety and immunogenicity.


Asunto(s)
Biosimilares Farmacéuticos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/uso terapéutico , Biosimilares Farmacéuticos/efectos adversos , Biosimilares Farmacéuticos/farmacocinética , Neoplasias de la Mama/patología , Femenino , Humanos , Neoplasias Gástricas/patología , Trastuzumab/efectos adversos
18.
Int J Mol Sci ; 18(9)2017 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-28885545

RESUMEN

Many of the tripartite motif (TRIM) proteins function as E3 ubiquitin ligases and are assumed to be involved in various events, including oncogenesis. In regard to tripartite motif-containing 44 (TRIM44), which is an atypical TRIM family protein lacking the RING finger domain, its pathophysiological significance in breast cancer remains unknown. We performed an immunohistochemical study of TRIM44 protein in clinical breast cancer tissues from 129 patients. The pathophysiological role of TRIM44 in breast cancer was assessed by modulating TRIM44 expression in MCF-7 and MDA-MB-231 breast cancer cells. TRIM44 strong immunoreactivity was significantly associated with nuclear grade (p = 0.033), distant disease-free survival (p = 0.031) and overall survival (p = 0.027). Multivariate analysis revealed that the TRIM44 status was an independent prognostic factor for distant disease-free survival (p = 0.005) and overall survival (p = 0.002) of patients. siRNA-mediated TRIM44 knockdown significantly decreased the proliferation of MCF-7 and MDA-MB-231 cells and inhibited the migration of MDA-MB-231 cells. Microarray analysis and qRT-PCR showed that TRIM44 knockdown upregulated CDK19 and downregulated MMP1 in MDA-MB-231 cells. Notably, TRIM44 knockdown impaired nuclear factor-kappa B (NF-κB)-mediated transcriptional activity stimulated by tumor necrosis factor α (TNFα). Moreover, TRIM44 knockdown substantially attenuated the TNFα-dependent phosphorylation of the p65 subunit of NF-κB and IκBα in both MCF-7 and MDA-MB-231 cells. TRIM44 would play a role in the progression of breast cancer by promoting cell proliferation and migration, as well as by enhancing NF-κB signaling.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Proteínas Portadoras/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Adulto , Anciano , Biomarcadores de Tumor , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Proteínas Portadoras/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Unión Proteica
19.
Clin Cancer Res ; 23(19): 5769-5778, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28679773

RESUMEN

Purpose: Bevacizumab, an antibody against endothelial growth factor, is a key but controversial drug in the treatment of metastatic breast cancer. We, therefore, aimed to determine the intrinsic resistance to bevacizumab at the physiologic and molecular levels in advanced breast cancer using PET, dynamic contrast-enhanced MRI, diffuse optical spectroscopic imaging (DOSI), and multiplex cytokine assays.Experimental Design: In total, 28 patients diagnosed with advanced stage III/IV breast cancer receiving single-agent bevacizumab for 1 week followed by paclitaxel combined with bevacizumab underwent 18F-fluorodeoxyglucose (FDG)-PET, 18F-fluoromisonidazole (FMISO)-PET, and MRI at both baseline and two courses after treatment initiation. Hemodynamic measurement using DOSI and blood sample collection were performed at baseline and multiple times during the first week after the initiation of single-agent bevacizumab. We distinguished nonresponders from responders by serial FDG-PET based on their glycolytic changes to chemotherapy.Results: Nonresponders showed significantly higher hypoxic activity on FMISO-PET and less tumor shrinkage than responders. Hemodynamic parameters showed higher tumor blood volume and a remarkable decrease in the tissue oxygen level in nonresponders compared with responders after the infusion of single-agent bevacizumab. Multiplex cytokine assays revealed increased plasma levels of both proangiogenic and hypoxia-related inflammatory cytokines in nonresponders and decreased levels in responders.Conclusions: Nonresponders exhibited a higher degree of angiogenesis with more severe hypoxia than responders during bevacizumab treatment. These findings demonstrated that the addition of bevacizumab to paclitaxel treatment under hypoxic conditions could be ineffective and may result in acute hypoxia and increased cytokine secretion associated with cancer progression. Clin Cancer Res; 23(19); 5769-78. ©2017 AACR.


Asunto(s)
Bevacizumab/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/efectos adversos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Citocinas/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Hipoxia/inducido químicamente , Hipoxia/patología , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Imagen Multimodal/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/patología , Tomografía de Emisión de Positrones/métodos , Radiofármacos/administración & dosificación , Carga Tumoral/efectos de los fármacos
20.
Invest New Drugs ; 35(6): 791-799, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28660549

RESUMEN

Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m2) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/secundario , Furanos/uso terapéutico , Cetonas/uso terapéutico , Vigilancia de Productos Comercializados , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Japón , Persona de Mediana Edad , Metástasis de la Neoplasia , Resultado del Tratamiento
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