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1.
Int J Cancer ; 146(2): 321-328, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30839100

RESUMO

The absolute risk reduction by prophylaxis in chemotherapy-induced febrile neutropenia (FN) is largest in patients at highest underlying risk. Therefore, reliable predictive models are needed. Here, we develop and validate such a model for risk of FN during chemotherapy cycles 2-6. A prediction score for risk of FN during the first cycle has recently been published. Patients with solid cancers initiating first-line chemotherapy in 2010-2016 were included. Cycle-specific risk factors were assessed by Poisson regression using generalized estimating equations and random split sampling. The derivation cohort included 4,590 patients treated with 15,419 cycles, wherein 326 (2.1%) FN events occurred. Predictors of FN in multivariable analyses were: higher predicted risk of FN in the first cycle, platinum- or taxane-containing therapies, concurrent radiotherapy, treatment in cycle 2 compared to later cycles, previous FN or neutropenia and not receiving granulocyte colony-stimulating factors. Each predictor added between -2 and 8 points to each patient's score (median score 4; interquartile range, 1-6). The incidence rate ratios for developing FN in the intermediate (score 1-4), high (score 5-6) and very high risk groups (score ≥7) were 7.8 (95% CI, 2.4-24.9), 18.6 (95% CI, 5.9-58.8) and 51.7 (95% CI, 16.5-162.3) compared to the low risk group (score ≤0), respectively. The score had good discriminatory ability with a Harrell's C-statistic of 0.78 (95% CI, 0.76-0.80) in the derivation and 0.75 (95% CI, 0.72-0.78) in the validation cohort (patient n = 2,295, cycle n = 7,670). The Cycle-Specific Risk of FEbrile Neutropenia after ChEmotherapy score is the first published method to estimate cycle-specific risk of FN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Modelos Biológicos , Neoplasias/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/etiologia , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Dinamarca/epidemiologia , Esquema de Medicação , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Compostos de Platina/administração & dosagem , Compostos de Platina/efeitos adversos , Distribuição de Poisson , Medição de Risco/métodos , Fatores de Risco , Taxoides/administração & dosagem , Taxoides/efeitos adversos
2.
N Engl J Med ; 381(26): 2506-2518, 2019 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-31566937

RESUMO

BACKGROUND: The efficacy and safety of cabazitaxel, as compared with an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear. METHODS: We randomly assigned, in a 1:1 ratio, patients who had previously received docetaxel and an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide) to receive cabazitaxel (at a dose of 25 mg per square meter of body-surface area intravenously every 3 weeks, plus prednisone daily and granulocyte colony-stimulating factor) or the other androgen-signaling-targeted inhibitor (either 1000 mg of abiraterone plus prednisone daily or 160 mg of enzalutamide daily). The primary end point was imaging-based progression-free survival. Secondary end points of survival, response, and safety were assessed. RESULTS: A total of 255 patients underwent randomization. After a median follow-up of 9.2 months, imaging-based progression or death was reported in 95 of 129 patients (73.6%) in the cabazitaxel group, as compared with 101 of 126 patients (80.2%) in the group that received an androgen-signaling-targeted inhibitor (hazard ratio, 0.54; 95% confidence interval [CI], 0.40 to 0.73; P<0.001). The median imaging-based progression-free survival was 8.0 months with cabazitaxel and 3.7 months with the androgen-signaling-targeted inhibitor. The median overall survival was 13.6 months with cabazitaxel and 11.0 months with the androgen-signaling-targeted inhibitor (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.89; P = 0.008). The median progression-free survival was 4.4 months with cabazitaxel and 2.7 months with an androgen-signaling-targeted inhibitor (hazard ratio for progression or death, 0.52; 95% CI, 0.40 to 0.68; P<0.001), a prostate-specific antigen response occurred in 35.7% and 13.5% of the patients, respectively (P<0.001), and tumor response was noted in 36.5% and 11.5% (P = 0.004). Adverse events of grade 3 or higher occurred in 56.3% of patients receiving cabazitaxel and in 52.4% of those receiving an androgen-signaling-targeted inhibitor. No new safety signals were observed. CONCLUSIONS: Cabazitaxel significantly improved a number of clinical outcomes, as compared with the androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who had been previously treated with docetaxel and the alternative androgen-signaling-targeted agent (abiraterone or enzalutamide). (Funded by Sanofi; CARD ClinicalTrials.gov number, NCT02485691.).


Assuntos
Antagonistas de Androgênios/administração & dosagem , Androstenos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Androstenos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Prednisona/administração & dosagem , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/mortalidade , Taxoides/efeitos adversos
4.
Cancer Treat Rev ; 79: 101885, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31442939

RESUMO

BACKGROUND: Cervical cancer is one of the most common malignancies diagnosed during pregnancy. Taxanes administration has been established as theurapetic regimen in non pregrant women. OBJECTIVES: This systemic review and meta-analysis aims to synthesize all available data from cervical cancer series in pregnant women and evaluate the efficacy and safety of taxanes during pregnancy. SEARCH STRATEGY: Eligible articles were identified by a search of ClinicalTrial.gov and MEDLINE databases for the period 01/01/2000 up to 31/11/2017; The algorithm consisted of a predefined combination of the words "cervical", "cancer", "taxanes" and "pregnancy". SELECTION CRITERIA: PRISMA guidelines were applied in this study. The literature search and data extraction from all studies that examined the efficacy and safety of taxanes in pregnancy, were done by two independent investigators. Quantitative synthesis of the published articles was performed. DATA COLLECTION AND ANALYSIS: Overall eight articles were retrieved. In all cases (14 pregnancies, 14 newborns) the use of taxanes in combination with platinum derivatives resulted in the birth of alive neonates, with not any miscarriage. The taxane derivative used in all cases was paclitaxel, combined with Cisplatin (13 pregnancies) and Carboplatin (one pregnancy). RESULTS: Complete and partial response was achieved in 7.2% and 92.9% of cervical cancer patients. In the majority of cases chemotherapy was well tolerated. The median progression-free survival was 48.5 months. CONCLUSION: Taxanes administration during the 2nd and 3rd trimester of pregnancy is a safe choice.


Assuntos
Complicações Neoplásicas na Gravidez/tratamento farmacológico , Taxoides/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Estimativa de Kaplan-Meier , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/mortalidade , Prognóstico , Taxoides/administração & dosagem , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade
5.
Anticancer Res ; 39(8): 4411-4414, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366538

RESUMO

BACKGROUND/AIM: Cabazitaxel use has usually been limited to up to 10 cycles in most countries according to the protocol in the TROPIC trial. Therefore, clinical data on cabazitaxel use beyond 10 cycles is limited. The aim of this study was to report the therapeutic outcome of cabazitaxel chemotherapy administered for >10 cycles. PATIENTS AND METHODS: This study included 74 Japanese patients with prostate cancer between 2014 and 2017. Patients background, and treatment outcomes including PSA decline, progression-free survival, treatment-failure-free survival, overall survival, and adverse events were investigated, comparing patients treated with ≤10 and >10 cycles. RESULTS: Patients characteristics were favorable as indicated by the higher number of cycles of prior docetaxel chemotherapy, absence of pain, and absence of bony and visceral metastases among men who received >10 cycles of cabazitaxel. PSA response, progression-free survival, treatment-failure-free survival and overall survival were better among patients treated with >10 cycles of cabazitaxel compared to those treated with ≤10 cycles. The incidence of severe adverse events was similar between the two groups. CONCLUSION: Taken together, this study suggested that continuous chemotherapy with cabazitaxel beyond 10 cycles may be beneficial.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel/efeitos adversos , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/efeitos adversos , Resultado do Tratamento
6.
BMC Cancer ; 19(1): 720, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331293

RESUMO

BACKGROUND: Interstitial pneumonitis is a rare reaction in a previously irradiated area of pulmonary or thoracic lesion after treatment with anticancer drugs such as taxanes. CASE PRESENTATION: A 66-year-old man presented with a fever and dyspnea after treatment with cabazitaxel for castration-resistant prostate cancer. He was treated with an intravenous broad-spectrum antimicrobial agent, however he complained of dyspnea and had a pulse oximetric saturation of 80% while breathing room air. The patients had been treated for bone metastases with 37.5 Gy to the thoracic spine (Th 7) as a local radiotherapy. Radiological images showed pulmonary interstitial opacities in the irradiated field of the both lungs. The steroid pulse therapy was started. The patient's dyspnea disappeared and the interstitial opacities had also improved. CONCLUSIONS: This report is a case of interstitial pneumonitis in a castration-resistant prostate cancer patient receiving cabazitaxel after thoracic radiation therapy.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Pulmonares Intersticiais/induzido quimicamente , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Administração Intravenosa , Idoso , Antineoplásicos/administração & dosagem , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Dispneia/tratamento farmacológico , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/tratamento farmacológico , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Taxoides/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
BMC Cancer ; 19(1): 625, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238987

RESUMO

BACKGROUND: Chemotherapy may be a valuable treatment option as neoadjuvant treatment for locally advanced penile cancer according to some previous studies, but the rarity of the sample and the Lack of large-scale clinical trials hampered the attempt to establish a solid evidence base for its routine use. The purpose of this study was to evaluate the efficacy of the neoadjuvant chemotherapy combined with a ITP regimen including docetaxel, cisplatin and ifosfamide for treating advanced penile cancer patients. METHODS: A total of 19 patients who were classified into advanced penile cancer (PN3) received neoadjuvant chemotherapy of ITP regimen from June 2009 to June 2016 in our hospital. RESULTS: After chemotherapy 12 patients had a partial response (PR), 5 had stable disease (SD) and progressive disease (PD) in 2 cases. The 12 responders underwent penectomy, bilateral inguinal lymphadenectomy (ILND) and pelvic lymph node dissection (LPLND). In contrast, 7 cases who were non-responsive received palliative local radiotherapy. After a median follow-up of 30.6 months, there was statistically significant improvement in median PFS and OS among patients who experienced an objective response to neoadjuvant chemotherapy (group A) compared with those patients who did not respond to chemotherapy (group B) (log-rank test; P < 0.001). CONCLUSION: Neoadjuvant docetaxel, cisplatin and ifosfamide chemotherapy gave 63% (12/19) of patients who were diagnosed with stage n3 penile cancer the chance of radical resection of metastases, and their OS and PFS were significantly higher than those who could not be operated on and the therapeutic dose, toxic and side effects are acceptable in the Chinese Han population. Therefore, neoadjuvant ITP chemotherapy in the treatment of stage T3 penile cancer patients may have cheerful prospects in the Chinese Han population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Metástase Linfática/patologia , Neoplasias Penianas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Progressão da Doença , Docetaxel/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Canal Inguinal , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Penianas/mortalidade , Neoplasias Penianas/patologia , Pênis/cirurgia , Taxoides/administração & dosagem , Taxoides/efeitos adversos
8.
Anticancer Res ; 39(6): 3089-3094, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177153

RESUMO

BACKGROUND/AIM: Limited information is available to help physicians decide when to introduce cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) patients. The objective of this study was to assess the optimal timing of cabazitaxel introduction. PATIENTS AND METHODS: The clinical outcomes of 66 mCRPC patients receiving cabazitaxel following failure of docetaxel were retrospectively analyzed. RESULTS: Among the parameters possibly affecting the timing of cabazitaxel introduction, only an increased prostate-specific antigen (PSA) value from the diagnosis of CRPC had a significant impact on overall survival (OS) after the introduction of cabazitaxel. Furthermore, there was a significant correlation between the increased PSA value from the diagnosis of CRPC and the baseline PSA value at cabazitaxel introduction. Multivariate analysis showed that only the baseline PSA value at cabazitaxel introduction is an independent predictor of OS. CONCLUSION: A comparatively low PSA value could be an alternative index suggesting the optimal timing for cabazitaxel introduction.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Esquema de Medicação , Humanos , Japão , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxoides/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
10.
BMC Cancer ; 19(1): 562, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185946

RESUMO

BACKGROUND: Cabazitaxel (CBZ) chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) is believed to be palliative because the radiological response rate is low and a durable response is rare. Here, we describe a rare case of a patient with mCRPC who was treated with CBZ chemotherapy and showed a durable radiological response and a complete biochemical response. CASE PRESENTATION: A 43-year-old man with prostate cancer and metastasis of the pubic bone underwent neoadjuvant androgen deprivation and docetaxel therapy, followed by laparoscopic prostatectomy, extended lymphadenectomy, and metastatectomy in 2014. Pathological examination revealed residual adenocarcinoma in the prostate and pubic bone (pathological T stage 3b, positive surgical margin). Following the operation, he received adjuvant radiation therapy (66 Gy) to the pelvic floor. His serum prostate-specific antigen (PSA) level decreased to < 0.01 ng/mL but gradually increased following docetaxel chemotherapy. Imaging findings indicated five tiny nodules in the bilateral lungs. Biopsy specimens are difficult to obtain and might not reflect the precise extent of the disease owing to heterogeneity in patients with CRPC. Thus, we performed liquid biopsy to isolate circulating tumor cells (CTCs), and overall 156 CTCs were detected per 7.5 mL. Almost all CTCs were androgen receptor-negative in the nucleus. We diagnosed the five nodules as lung metastases from docetaxel-resistant CRPC with few AR-signaling-dependent cancer cells. The patient was initiated on CBZ chemotherapy (25 mg/m2) according to the standard protocol in August 2016, instead of using a second-generation AR-targeting agent. After 2 cycles of CBZ chemotherapy, PSA level decreased to < 0.01 ng/mL and the lung metastases completely disappeared, with a reduced CTC count of < 5. To date, the patient has been receiving intermittent CBZ chemotherapy. CONCLUSIONS: We presented a rare case of a patient with mCRPC who was successfully treated with early CBZ chemotherapy. The early detection of metastasis using liquid biopsy enabled the introduction of early CBZ chemotherapy for docetaxel-resistant mCRPC.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/secundário , Antineoplásicos/uso terapêutico , Detecção Precoce de Câncer , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Taxoides/uso terapêutico , Adenocarcinoma de Pulmão/diagnóstico , Adulto , Antineoplásicos/administração & dosagem , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Biópsia Líquida , Neoplasias Pulmonares/diagnóstico , Masculino , Células Neoplásicas Circulantes , Antígeno Prostático Específico/sangue , Receptores Androgênicos/metabolismo , Taxoides/administração & dosagem , Resultado do Tratamento
11.
Breast Cancer Res Treat ; 176(3): 631-635, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31115845

RESUMO

PURPOSE: While some studies show improved outcomes in clinical trial participants as compared to non-participants, existence of such a trial effect has not been proved precisely. METHODS: This was a prospective cohort study to compare the prognoses for participants in the randomized controlled trial (SELECT BC) and non-participants. SELECT BC compared S-1 and taxane as first-line treatment for metastatic breast cancer. Non-participants were all patients who met the eligibility criteria of SELECT BC and who had been requested to participate in that trial by attending doctors and declined. The study aimed to compare the prognoses between participants and non-participants. The primary endpoint was median overall survival. RESULTS: The median OS in participants was significantly superior to that in non-participants with a statistically significant difference (36.8 months vs. 25.2 months. HR 1.48, p = 0.022). A similar result was obtained when only patients who received the same chemotherapy (S-1 or taxane) used in SELECT BC after declining participation were assumed as non-participants (36.8 months vs. 22.0 months. HR 2.03, p = 0.006). CONCLUSIONS: This study may suggest the existence of a trial effect, in which, for a given treatment, participation in a clinical trial is associated with a better outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Participação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Terapia Combinada , Combinação de Medicamentos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Taxa de Sobrevida , Taxoides/administração & dosagem , Tegafur/administração & dosagem , Resultado do Tratamento
12.
Breast Cancer Res Treat ; 176(3): 607-615, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069589

RESUMO

AIM: To evaluate the pCR rate and toxicity of the addition of weekly carboplatin (Cp) to paclitaxel (wP) and dose-dense (dd) epirubicin/cyclophosphamide (EC) in an open-label phase II study in TNBC patients. METHODS: Patients were included if they had stage II and III TNBC and received wP (80 mg/m2/week) concurrent with weekly Cp (AUC = 2) for 12 weeks, followed by bi-weekly epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) plus granulocyte colony-stimulating factor (G-CSF) for four cycles, followed by surgery. The primary endpoint was the rate of pCR [(ypT0/isypN0)]. Secondary endpoints included safety and drug delivery. RESULTS: Sixty-three eligible patients were included. Median age was 51 years (range 29-74); 88.9% had stage II disease, 46% were clinically node positive, and 77.8% had grade 3 tumors. Fifty-four percent achieved a pCR. Twelve percent missed two or more doses of wP, whereas at least two cycles of EC were missed in 9.5%. The rate of tolerance without delays or dose reductions is very low (16%). Sixty-two percent had G3/4 neutropenia. Febrile neutropenia occurred in 18 patients of which more than eighty percent occurred during EC despite primary prophylaxis with G-CSF. Thrombocytopenia grade 3/4 was noticed in 11 pts. Three patients developed grade 3 peripheral neuropathy. CONCLUSION: The addition of weekly carboplatin to neoadjuvant paclitaxel and dd EC leads to a pCR rate comparable to prior studies (54%). However, hematological toxicity and febrile neutropenia rate was unexpectedly high. Future investigations could focus on reversing the sequence, which may lead to better hematological tolerability.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bélgica , Biomarcadores Tumorais , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carboplatina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Análise de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/mortalidade
13.
J BUON ; 24(2): 650-655, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128019

RESUMO

PURPOSE: Advanced gastric cancer has a dismal prognosis. Platin/5-fluorouracil (PF) combination chemotherapy is the main treatment modality for metastatic gastric cancer patients. Third drug addition to PF is a controversial issue. The aim of this study was to evaluate the predictive role of tumor localization and histopathology on choosing three- or two-drug combination regimens. METHODS: This study was designed as a hospital-based retrospective observational case-series study. A total of 516 patients with advanced gastric cancer has been treated at eight different oncology centers in Turkey between 2006 and 2016. Laboratory results and demographic data were collected and analyzed. RESULTS: The median patient age was 59 years (range 25-85). Proximal intestinal and distal intestinal cancers were found in 357 (69.2 %) and 159 (30.8 %) patients, respectively. 5-fluorouracil (5FU) and cisplatin (PF) and cisplatin+5FU+docetaxel (PFtax, also known as DCF) were administered to 240 (46.5%) and 276 (53.5%) patients, respectively. Median progression free survival (PFS) was 5.0 (95% CI 4.21-5.29) and 8 months (95% CI 7.22-8.77) for PF and PFtax groups, respectively (p=0.000). When tumor localization was used as stratum in PFS survival, PFtax produced significantly higher PFS rates only in distal intestinal type gastric cancer compared to PF (p=0.000). Median overall survival (OS) was 12 (95% CI 9.8-14.2) and 16 months (95% CI 13.6-18.4) for the PF and PFtax groups, respectively (p=0.01). When tumor localization was used as stratum in OS, PFtax showed significantly higher OS rates only in the distal intestinal type gastric cancer compared to PF (p=0.01) Conclusion: Pathology and tumor location in gastric cancer may affect the outcome. Addition of taxanes as a third drug may significantly increase PFS and OS rates only in distal intestinal type gastric cancer but not in patients with proximal type gastric cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Intestinos/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Taxoides/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Intestinos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Resultado do Tratamento , Turquia/epidemiologia
14.
J BUON ; 24(2): 516-521, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31127999

RESUMO

PURPOSE: This article focuses on how the status of hormone receptors (HR) influences the efficacy of trastuzumab in patients with metastatic HER2-positive breast cancer treated with first-line trastuzumab in combination with taxane-based chemotherapy. METHODS: A prospective study was carried out at the Clinic for Oncology, Clinical Centre in Nis, from January 2015 to until June 2018. A total of 121 patients were treated with first-line trastuzumab in combination with taxane-based chemotherapy. None of the patients from the HR-positive group received hormonotherapy after completion of chemotherapy with trastuzumab. RESULTS: Clinical benefit rate was present in 76% of the patients, including partial response (PR) in 37%, stable disease (SD) in 38%, and complete response (CR) in almost 8% of the patients. Progressive disease (PD) occurred in almost a quarter of the patients, i.e. 24%. Progression-free survival (PFS) in the entire group of patients amounted to 9 months, whereas overall survival (OS) was 30 months. PFS in the HR-negative tumor group was significantly longer (13 months) compared to 8 months in the HR-positive tumor group (p<0.0001; HR 0.49;95% CI 0.31-0.69). Furthermore, OS was significantly longer in the HR-negative tumor group (34 months), compared to 26 months in the HR-positive tumor group (p=0.0073, HR 0.57; 95% CI 0.36-0.90). CONCLUSIONS: These data indicate a different response to anti-HER2 therapy in patients with HER2+ metastatic breast cancer (MBC) according to HR status, thus emphasizing that ER most likely represents an escape pathway for the response to anti-HER2 target therapy and vice versa. Combining hormonotherapy with anti-HER2 therapy surely represents a promising strategy which could help overcome resistance to trastuzumab and other anti-HER2 agents.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Trastuzumab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Prospectivos , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Trastuzumab/efeitos adversos , Resultado do Tratamento
15.
J BUON ; 24(2): 522-528, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128000

RESUMO

PURPOSE: To observe the efficacy of neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC) and to investigate the effect of Annexin A3 (ANXA3) expression. METHODS: 158 patients with BC treated in Yantai Yuhuangding Hospital from September 2015 to December 2017 were retrospectively analyzed. Among them, 83 cases were treated with epirubicin + cyclophosphamide + 5-fluorouracil (CEF group), 75 cases with epirubicin + cyclophosphamide + docetaxel (TEC group), with 3 cycles of chemotherapy. The efficacy and adverse reactions of the two NAC regimens were compared and analyzed. Tissue specimens were collected before and 10 days after the administration of chemotherapy in order to detect the expression of ANXA3 by qRT-PCR in each group. RESULTS: There were significant differences in the rates of complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) between the two groups (z=10.716, p=0.013). The clinical effectiveness rate in the TEC group was significantly higher than that in the CEF group (p<0.05). There was no difference in the pathology grade between the two groups (p>0.05); however, the pathological effective rate in the TEC group was significantly higher than that in the CEF group (p<0.05). There was no difference in the rate of bone marrow suppression between the two groups (p>0.05). While there was no difference in the relative expression of ANXA3 between the two groups before chemotherapy, the relative expression of ANXA3 in the TEC group was lower than that in the CEF group after NAC (p<0.05). The relative expression in both groups after chemotherapy was lower than that before NAC (P<0.05). CONCLUSION: Compared with CEF regimen, NAC with TEC regimen can improve the clinical and pathological effectiveness rate, inhibit the expression of ANXA3, and improve the prognosis of patients, thus having a certain application prospect in NAC.


Assuntos
Anexina A3/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Taxoides/administração & dosagem , Taxoides/efeitos adversos
16.
Molecules ; 24(9)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052317

RESUMO

Paclitaxel is highly effective at killing many malignant tumors; however, the development of drug resistance is common in clinical applications. The issue of overcoming paclitaxel resistance is a difficult challenge at present. In this study, we developed nano drugs to treat paclitaxel-resistant lung adenocarcinoma. We selected cabazitaxel and ß-elemene, which have fewer issues with drug resistance, and successfully prepared cabazitaxel liposome, ß-elemene liposome and cabazitaxel-ß-elemene complex liposome with good flexibility. The encapsulation efficiencies of cabazitaxel and ß-elemene in these liposomes were detected by precipitation microfiltration and microfiltration centrifugation methods, respectively. Their encapsulation efficiencies were all above 95%. The release rates were detected by a dialysis method. The release profiles of cabazitaxel and ß-elemene in these liposomes conformed to the Weibull equation. The release of cabazitaxel and ß-elemene in the complex liposome were almost synchronous. The pharmacodynamics study showed that cabazitaxel flexible liposome and ß-elemene flexible liposome were relatively good at overcoming paclitaxel resistance on paclitaxel-resistant lung adenocarcinoma. As the flexible complex liposome, the dosage of cabazitaxel could be reduced to 25% that of the cabazitaxel injection while retaining a similar therapeutic effect. It showed that ß-elemene can replace some of the cabazitaxel, allowing the dosage of cabazitaxel to be reduced, thereby reducing the drug toxicity.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Lipossomos , Sesquiterpenos/administração & dosagem , Sesquiterpenos/farmacocinética , Taxoides/administração & dosagem , Taxoides/farmacocinética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Lipossomos/química , Camundongos , Estrutura Molecular , Paclitaxel/farmacologia , Tamanho da Partícula , Sesquiterpenos/química , Taxoides/química , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Breast Cancer Res Treat ; 175(3): 659-666, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30937656

RESUMO

PURPOSE: To evaluate and compare the efficacy and safety of the taxane plus anthracycline (TA) regimen vs. the taxane plus anthracycline plus cyclophosphamide (TAC) regimen as adjuvant chemotherapy in Chinese patients with node-positive breast cancer (BCa). METHODS: Patients with BCa (n = 640) were recruited between January 2010 and June 2012. All patients were randomized to receive six cycles of adjuvant therapy with the TA or TAC regimen. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS), quality of life (QoL), and chemotherapy-related toxicity. Finally, 630 patients were evaluable, with a median follow-up of 70 months. RESULTS: There were no differences in the 70-month median DFS and OS between the two groups (DFS: TA 79.7% vs. TAC 75.6%, P = 0.371; OS: TA vs. TAC, 85.1% vs. 87.6%, P = 0.271). The TA group had lower frequencies grade III/IV vomiting (TA vs. TAC, 11.7% vs. 18.1%, P = 0.025) and nausea (13.0% vs. 19.4%, P = 0.031). The health-related QoL score was higher in the TA group (74.1 ± 5.3 vs. 67.9 ± 4.4, P = 0.001 vs. TAC). CONCLUSIONS: In the adjuvant setting, compared with the TAC regimen, the TA regimen exhibits no significant difference with respect to DFS and OS in Chinese patients with node-positive BCa. On the other hand, TA is associated with less severe adverse events, lower economic burden, and better QoL.


Assuntos
Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Ciclofosfamida/administração & dosagem , Taxoides/administração & dosagem , Adulto , Idoso , Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , China , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Taxoides/efeitos adversos , Resultado do Tratamento
18.
J Int Med Res ; 47(5): 2207-2214, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30991863

RESUMO

OBJECTIVE: To investigate the safety and efficacy of acitinib mesylate combined with chemotherapy in the treatment of patients with gastroesophageal junction adenocarcinoma. METHODS: A total of 119 patients with gastroesophageal junction adenocarcinoma were enrolled and randomized into an experimental group (n = 60) and a control group (n = 59). Both groups were treated with a combination of taxane, irinotecan and fluorouracil, while the experimental group also received acitinib mesylate. The clinical efficacy, survival time and adverse reactions of patients in two groups were recorded and analyzed. RESULTS: The total remission rate in the experimental group and the control group was 15.79% and 3.23%, respectively; the disease control rate was 73.68% and 54.84%, respectively; and progression-free survival was 3.72 months (1-13.5 months) and 3.04 months (1-6 months), respectively. Overall survival was 13.66 months (5-24 months) and 10.08 months (6.5-19.5 months), in the experimental group and the control group, respectively. In addition, the incidence of adverse events in the experimental group was significantly lower than that in the control group. CONCLUSION: Apatinib mesylate combined with chemotherapy for the treatment of patients with gastroesophageal junction adenocarcinoma was safe and effective, with improved survival benefit compared with control.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/patologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Cisplatino/administração & dosagem , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/efeitos dos fármacos , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano/administração & dosagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Piridinas/administração & dosagem , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagem
19.
Support Care Cancer ; 27(12): 4753-4762, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30972646

RESUMO

CONTEXT/OBJECTIVES: This is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy. METHODS: Cancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score. RESULTS: There was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p < 0.001 and r = - 0.518, p < 0.001, respectively; T3: r = - 0.699; p < 0.001 and r = - 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score). CONCLUSION: The MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Compostos Organoplatínicos/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diferença Mínima Clinicamente Importante , Síndromes Neurotóxicas/diagnóstico , Compostos Organoplatínicos/administração & dosagem , Doenças do Sistema Nervoso Periférico/diagnóstico , Qualidade de Vida , Inquéritos e Questionários , Taxoides/administração & dosagem , Taxoides/efeitos adversos
20.
Zhonghua Zhong Liu Za Zhi ; 41(2): 118-123, 2019 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-30862141

RESUMO

Objective: To investigate the therapeutic effect of Jin Long Capsule (JLC) combined with neoadjuvant chemotherapy on the invasive breast cancer, and to explore the mechanism of JLC in inhibiting multidrug resistance of breast cancer. Methods: 200 patients were divided into experimental group and control group (100 cases per group). The control group used TEC regimen for neoadjuvant chemotherapy. And the experimental group was treated with TEC regimen combined with oral JLC. According to the Miller & Payne grading system (MP), the efficacy of neoadjuvant chemotherapy was evaluated based on histopathological changes of breast cancer after neoadjuvant chemotherapy. Adverse effect was evaluated according to the classification criteria of the National Cancer Institute of the United States-The Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The expression of P-glycoprotein (P-gp), glutathione thiol transferase (GST)-π and topoisomerase Ⅱα (TopoⅡα) in breast cancer tissues before and after neoadjuvant chemotherapy were detected by immunohistochemical staining. Results: There were 83 effective cases (83%) in the experimental group, which was higher than that in the control group (65.0%, P<0.05). The incidence of leukopenia, gastrointestinal reactions and alopecia in grade 3 to 4 of the experimental group were lower than those of the control group (all P<0.05). The positive rates of P-gp, GST-π and TopoⅡα expression in the control group were 65.0% (65/100), 61.0% (61/100) and 69.0% (69/100), respectively, and they were 80.6% (75/93), 78.5% (73/93) and 37.6% (35/93) after chemotherapy. The positive rates of P-gp and GST-π expression were significantly higher than those before chemotherapy (both P<0.05), whereas the positive rate of TopoⅡα expression was significantly lower than that before chemotherapy (P<0.05). In the experimental group, the positive rates of P-gp, GST-π and TopoⅡα expression before chemotherapy were 62.0% (62/100), 63.0% (63/100) and 69.0% (69/100), respectively, while after chemotherapy, they were 68.2% (60/88), 67.0% (59/88) and 63.6% (56/88). There was no significant difference in the positive rates and expression intensity of P-gp, GST-π and TopoⅡα before and after the chemotherapy (P>0.05). Conclusion: Jin Long Capsule (JLC) can inhibit multidrug resistance, improve the efficacy of neoadjuvant chemotherapy, and reduce adverse reactions of breast cancer.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Medicamentos de Ervas Chinesas/uso terapêutico , Terapia Neoadjuvante , Subfamília B de Transportador de Cassetes de Ligação de ATP , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Cápsulas , Quimioterapia Adjuvante/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , DNA Topoisomerases Tipo II/metabolismo , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Glutationa Transferase/metabolismo , Humanos , Terapia Neoadjuvante/efeitos adversos , Taxoides/administração & dosagem , Taxoides/efeitos adversos
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