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1.
Yonsei Med J ; 61(4): 284-290, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233170

RESUMO

PURPOSE: We evaluated whether adding bevacizumab to current platinum-based chemotherapy could improve clinical outcomes without affecting safety. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with pathologically confirmed ovarian cancer who received neoadjuvant chemotherapy (NAC) at Yonsei Cancer Hospital. We divided the patients into groups based on the use of bevacizumab for NAC (CP group: carboplatin+paclitaxel vs. BCP group: bevacizumab+carboplatin+paclitaxel) and compared patient characteristics, responses to NAC, and surgical and survival outcomes between the two groups. Overall, 88 patients in the CP group and 16 patients in the BCP group received NAC. The primary endpoint was survival outcomes. Complete resection rate after interval debulking surgery (IDS), cancer antigen 125 (CA-125) normalization after NAC, and chemotherapy response score were secondary endpoints. RESULTS: After NAC treatment, all patients underwent IDS. There were no significant differences in adverse events during NAC or postoperative complications between the two groups (p=0.293 and p=0.485, respectively). There were also no significant differences in CA-125 normalization after NAC (42.0% vs. 43.8%, p=0.899) or complete resection rate after IDS (47.7% vs. 56.3%, p=0.530). However, although the BCP group did not show longer overall survival (OS) (log-rank p=0.854), they had significantly longer progression-free survival (PFS) than the CP group (log-rank p=0.048). CONCLUSION: Bevacizumab-containing NAC might be safe and provide longer PFS than chemotherapy alone in patients with advanced ovarian cancer. However, further study is necessary to investigate the impact of bevacizumab-containing NAC on OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Epitelial do Ovário/terapia , Terapia Neoadjuvante , Neoplasias Ovarianas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Antígeno Ca-125 , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Complicações Pós-Operatórias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
2.
Anticancer Res ; 40(3): 1619-1624, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132065

RESUMO

BACKGROUND: Prognosis of metastatic malignant peripheral nerve sheath tumor (MPNST) is poor and the role of chemotherapy is controversial. There has been no report of metastatic MPNST with a good prognosis without surgery for metastases. CASE REPORT: A 40-year-old man with neurofibromatosis type 1 (NF1)-related MPNST on his shoulder with multiple lung metastases visited our hospital. After two cycles of chemotherapy with ifosfamide, carboplatin and etoposide (ICE), the primary lesion and lung metastases had shrunk. The primary lesion was resected with negative margins. Subsequently, 'gradual subtraction' ICE was administered, wherein the dose was reduced and the treatment interval was increased. After 14 courses of ICE over a period of 2 years, the lung metastases disappeared; there has been no recurrence for over 12 years. CONCLUSION: ICE can be an excellent, inexpensive treatment for NF1-related MPNST. 'Gradual subtraction' chemotherapy allowed us to maintain long-term efficacy, induce tumor dormancy, and reduce side-effects.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Etoposídeo/uso terapêutico , Ifosfamida/uso terapêutico , Neoplasias da Bainha Neural/tratamento farmacológico , Neurofibromatose 1/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carboplatina/farmacologia , Etoposídeo/farmacologia , Humanos , Ifosfamida/farmacologia , Masculino , Metástase Neoplásica , Neoplasias da Bainha Neural/patologia , Prognóstico
3.
Orv Hetil ; 161(11): 425-433, 2020 Mar.
Artigo em Húngaro | MEDLINE | ID: mdl-32148096

RESUMO

Introduction: Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The best survival rates are expected after surgical removal, thus the aim of a complex treatment is to achieve resecability in locally and locoregionally advanced disease. Aim: The primary purpose of this study was to evaluate if the neoadjuvant systemic treatment leads to better overall survival compared to irradiation solely. Method: From January 2015 to December 2018, we enrolled 28 patients diagnosed with irresecable, locally and locoregionally advanced high-risk endometrial carcinoma. Patients were treated by neoadjuvant paclitaxel-carboplatin, then radical hysterectomy, bilateral oophorectomy and lymphadenectomy were performed. Results: After administration of 6 cycles of carboplatin-paclitaxel, the control MR test showed tumor shrinkage in all patients. Complete resection was achieved in the case of every patient. Tumor residuum in lymph nodes was verified in 4 cases by pathological evaluation. The 2-year survival and the 2-year progression-free survival rates were 65,1% and 66,1%, respectively. The median overall survival was 16,5 months. Conclusion: Neoadjuvant treatment can be an effective approach in providing the conditions for complete tumor resection, which may result in survival advantage. Despite multimodal treatment, prognosis is poor. Orv Hetil. 2020; 161(11): 425-433.


Assuntos
Carboplatina/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/cirurgia , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapêutico , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Ovariectomia , Taxa de Sobrevida , Resultado do Tratamento
4.
Medicine (Baltimore) ; 99(8): e19226, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080119

RESUMO

Treatment options for recurrent glioblastoma are rare, with their response uncertain. This study aimed to determine the response of chemotherapy including bevacizumab in combination with vincristine and carboplatin for glioblastoma at first recurrence in a single-institution cohort.Clinical data of patients who received chemotherapy including bevacizumab, vincristine, and low-dose carboplatin for recurrent glioblastoma between 2008 and 2014 were analyzed. Differences between those who received combination chemotherapy (chemotherapy-positive) and those who did not (chemotherapy-negative) were estimated by Fisher exact test or Wilcoxon rank-sum test, as appropriate. Survival curves were estimated using the Kaplan-Meier method, and differences between survival curves were estimated by the log-rank test. Univariate analysis of treatment response for all recurrent glioblastoma patients and secondary recurrence patients under different conditions were evaluated using Wilcoxon rank-sum test or the Kruskal-Wallis test.Although mortality rates were similar between the chemotherapy-negative and chemotherapy-positive groups (26.7% vs 28.6%), median overall survival was significantly longer in the chemotherapy-positive group than the chemotherapy-negative group (P = .006). There were no chemotherapy-related serious complications such as gastrointestinal perforation, serious bleeding, or new-onset seizure during chemotherapy, whereas others side effects including proteinuria and hypertension were more common albeit well controlled by medication.This study revealed combination regimen of bevacizumab, vincristine, and low-dose carboplatin as a potentially effective therapeutic approach in recurrent glioblastoma. More in-depth understanding of the mechanism underlying this combination treatment and potential contribution of alternative genetic therapeutic in recurrent glioblastoma is necessary.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/mortalidade , Carboplatina/uso terapêutico , Feminino , Glioblastoma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Taiwan , Vincristina/uso terapêutico
5.
Cancer Immunol Immunother ; 69(3): 383-397, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31897661

RESUMO

The standard-of-care (SOC) first-line therapy for ovarian cancer (OC) patients is plagued with high relapse rates. Several studies indicated the immune system's prominent role changing the disease course in OC patients. Chemo-immunotherapy regimens, currently being explored, include oregovomab, which is a monoclonal antibody specific for the OC associated antigen carbohydrate/cancer antigen 125 (CA125) that yielded promising results when administered together with SOC in a previous study. The QPT-ORE-002 multi-site phase II randomized study demonstrated that in patients with advanced OC, oregovomab combined with first-line SOC improved overall and progression-free survival, compared to SOC alone. The study included an Italian cohort in which we demonstrated that adding oregovomab to SOC resulted in increased patient numbers with amplified CA125-specific CD8+T lymphocytes/ml peripheral blood counts, which might explain the improved therapeutic effect of SOC + oregovomab over SOC alone. Predictive for oregovomab efficacy was a less suppressive immune environment at baseline as indicated by low numbers of circulating myeloid-derived suppressor cells, subset type 4, and a low neutrophil-and-monocyte to lymphocyte ratio.


Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Imunoterapia/métodos , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Anticorpos Monoclonais Murinos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carboplatina/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Medicina de Precisão
7.
Mol Immunol ; 118: 99-109, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31862674

RESUMO

Immunosuppressive chemoresistance is a major barrier in lung cancer treatment. Tumor immunosuppressive environments mediated by myeloid-derived suppressor cells (MDSCs) play a key role in chemotherapy induced MDSC development and differentiation but their mechanistic role has not been elucidated. Here, we define a role for carboplatin based chemotherapy in potentiating an MDSC-dependent pathway that triggers the chemoresistance mechanism. Findings reveal MDSC differentiation and activation of IL-13/IL-33-mediated pathway through VCAM/RANTES following carboplatin treatment. Furthemore, secretion of T regulatory IL-10-producing CD4+Foxp3+ cells was increased followed by expression of co-inhibitory receptor TIGIT on T cells, leading to a dysfunctional T cell phenotype. These cells were characterized by an immunosuppressive phenotype with impaired activation, proliferation and cytokine production. Lung cancer tissues expressed CD155, which bound TIGIT receptors and inactivated CD8 T cells. This TIGIT expression on tumor-infiltrating T cells was found to be associated with tumor progression and was linked to functional exhaustion of T cells. In addition, the presence of plasmacytoid dendritic cells (pDCs) exposed to tumor-derived factors further enhanced tumor progression through IL-10 production and up-regulation of the inducible co-stimulatory ligand (ICOS-L). Deciphering these deranged immune mechanisms and how they are impacted by chemotherapy induction is essential for incorporation of novel immune-based strategies in order to restore immunity and inhibit the immunosuppressive phenotype of metastatic lung cancer.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Resistencia a Medicamentos Antineoplásicos/imunologia , Receptores Imunológicos/imunologia , Regulação para Cima/imunologia , Células A549 , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/imunologia , Antígenos Ly/imunologia , Antígeno CD11b/imunologia , Carboplatina/uso terapêutico , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Feminino , Proteínas Ligadas por GPI/imunologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Ativação Linfocitária/genética , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Transdução de Sinais/imunologia , Ativação Transcricional/imunologia
8.
Anticancer Res ; 39(12): 6819-6827, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810948

RESUMO

BACKGROUND/AIM: This Japanese multiple-center retrospective study aimed to examine the real-world treatment outcomes of the EXTREME regimen as a first-line therapy for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). PATIENTS AND METHODS: A total of 100 R/M SCCHN patients treated with the EXTREME regimen as first-line therapy were analyzed. The treatment outcomes were evaluated to compare patient and treatment characteristics with overall survival. RESULTS: Patients treated with carboplatin-based EXTREME regimen showed similar overall survival with less adverse effects compared to that of patients using cisplatin. The post-progression survival was significantly longer in patients treated with second-line treatment following the EXTREME regimen than in those without second-line treatment. CONCLUSION: The carboplatin-based EXTREME regimen was more feasible with similar treatment outcomes compared to cisplatin-based EXTREME regimen. In addition, subsequent lines of therapy contributed to improvement of survival for R/M SCCHN patients.


Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
9.
PLoS One ; 14(12): e0226350, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860688

RESUMO

BACKGROUND AND PURPOSE: The roles of surgery, chemotherapy, and parameters of radiation therapy for treating very rare central nervous system germ cell tumors (CNS-GCT) are still under discussion. We aimed to evaluate the survival and recurrence patterns of patients with CNS-GCT treated with chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy. MATERIALS AND METHODS: We reviewed the clinical outcomes of 20 consecutive patients with CNS-GCT treated with chemotherapy and intensity-modulated radiation therapy from 2004 to 2014 in two partner institutions. RESULTS: Twenty children with a median age of 12 years were included (16 males). Sixteen tumors were pure germinomas, and 4 were non-germinomatous germ cell tumors (NGGCT). All patients were treated with intensity-modulated radiation therapy guided by daily images, and 70% with volumetric intensity-modulated arc radiotherapy additionally. The median dose for the whole-ventricle was 25.2 Gy (range: 18-30.6 Gy) and 36 Gy (range: 30-54 Gy) for the tumor bed boost. The median post-radiation therapy follow-up was 57.5 months. There were 3 recurrences (2 NGGCT and 1 germinoma that recurred as a NGGCT), with 1 death from the disease and the other 2 cases each successfully rescued with chemotherapy and craniospinal irradiation. The overall survival at 5 years was 95% and disease-free survival was 85%. CONCLUSIONS: The results of this study suggest that the combined use of chemotherapy followed by whole ventricle irradiation with intensity-modulated radiation therapy is effective for CNS-GCTs, especially pure germinomas. Even being rescued with craniospinal irradiation, the NGGCT cases have markedly worse prognoses and should be more rigorously selected for localized treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/radioterapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/mortalidade , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Quimiorradioterapia , Criança , Irradiação Craniana , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Fracionamento da Dose de Radiação , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/mortalidade , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Resultado do Tratamento
11.
Bull Cancer ; 106(12): 1086-1093, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31582176

RESUMO

BACKGROUND: Testicular Germ Cell Tumors (TGCTs) represent the most frequent malignant tumour among young male adults. Orchiectomy alone cure 80% of stage I. Standard options after orchiectomy include radiotherapy (RT), chemotherapy (CT) by 1 cycle of carboplatin AUC 7 or active surveillance (SV) for seminomatous GCTs (SGCT) and retroperitoneal lymphadenectomy (RPLND), CT by 1 or 2 cycles of Bleomycine Etoposide Cisplatine (BEP) or active surveillance for nonseminomatous GCTs (NSGCT). Adjuvant treatments decrease the relapse rate after orchiectomy with substantial toxicities without any benefit on overall survival. Recent guidelines accorded utmost importance on SV rather than adjuvants strategies. The main objective of this study was to describe our current practice over the 10 past years in regard of these recommendations. METHODS: Data of 50 patients with stage I GCT treated in our institute were collected between 2006 and 2016. Demographic and anatomopathologic data were reported. Clinical practice in our center was analyzed during two periods [2006-2011] and [2012-2016] according to the European Association of Urology Guidelines in 2011. RESULTS: Patient's median age was 35.3 years. The analysis of clinical practice during the last 10 years showed that in SGCT, main treatment was RT than SV and CT. This option declined over the years (89% between 2006-2010 versus 53% between 2011-2016) whereas SV was more often employed (27% between 2011-2016 versus none between 2006-2010). Surveillance was used for 64% of NSGCT. CONCLUSIONS: In our center, RT was less used over the years for the benefit of SV which is recommended by guidelines.


Assuntos
Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Institutos de Câncer , Carboplatina/uso terapêutico , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , França , Humanos , Excisão de Linfonodo , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Orquiectomia/métodos , Vigilância da População , Radioterapia/tendências , Estudos Retrospectivos , Neoplasias Testiculares/patologia , Fatores de Tempo
12.
Gynecol Oncol ; 155(3): 400-405, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606285

RESUMO

OBJECTIVE: The role of secondary cytoreductive surgery (SCS) in platinum-sensitive recurrent ovarian cancer (PSROC) is still controversial. We investigated the role of SCS in PSROC patients with BRCA1/2 mutation (BRCAmut) who received platinum-based chemotherapy followed by olaparib maintenance. METHODS: This is a case-control study. Patients with first PSROC admitted to our Gynecologic Oncology Unit between 2014 and 2018 were identified. Main eligibility criteria: positive BRCA1/2 germline or somatic mutation status and olaparib maintenance at primary recurrence after response to platinum-based chemotherapy. Cases were those who received SCS followed by medical treatment (SCS-CT-OLA, group 1), controls were those who received medical treatment alone (CT-OLA, group 2). RESULTS: Overall, 46 patients were identified; 23 (50%) BRCAmut women undergoing SCS followed by platinum-based chemotherapy and olaparib maintenance were matched with 23 (50%) BRCAmut women who only received medical treatment. Groups were well balanced: no statistical differences were found with regard of age, mutational status, treatment's approach at diagnosis, timing and patterns of disease presentation at recurrence. Median time to first subsequent therapy (TFST) was significantly longer in the SCS-CT-OLA than in the CT-OLA group (42 months vs 16 months; p = 0.05). Also, SCS-CT-OLA patients had the best post-recurrence survival (PRS), with a 3-year PRS of 79% in SCS-CT-OLA group versus 42% in CT-OLA group (p = 0.02). CONCLUSIONS: SCS increases TFST and PRS in PSROC patients with BRCAmut candidate for olaparib maintenance after platinum-based chemotherapy. Prospective studies are needed. In the era of personalized medicine, indication to SCS should be individualized.


Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Estudos de Casos e Controles , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Doxorrubicina/administração & dosagem , Feminino , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Humanos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Paclitaxel/administração & dosagem
13.
Int J Mol Sci ; 20(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370215

RESUMO

Dedifferentiated endometrial carcinoma (DDEC) is defined as an undifferentiated carcinoma admixed with differentiated endometrioid carcinoma (Grade 1 or 2). It has poor prognosis compared with Grade 3 endometrioid adenocarcinoma and is often associated with the loss of mismatch repair (MMR) proteins, which is seen in microsatellite instability (MSI)-type endometrial cancer. Recent studies have shown that the effectiveness of immune checkpoint inhibitor therapy is related to MMR deficiency; therefore, we analyzed the immunophenotype (MMR deficient and expression of PD-L1) of 17 DDEC cases. In the undifferentiated component, nine cases (53%) were deficient in MMR proteins and nine cases (53%) expressed PD-L1. PD-L1 expression was significantly associated with MMR deficiency (p = 0.026). In addition, the presence of tumor-infiltrating lymphocytes (CD8+) was significantly associated with MMR deficiency (p = 0.026). In contrast, none of the cases showed PD-L1 expression in the well-differentiated component. Our results show that DDEC could be a target for immune checkpoint inhibitors (anti PD-L1/PD-1 antibodies), especially in the undifferentiated component. As a treatment strategy for DDEC, conventional paclitaxel plus carboplatin and cisplatin plus doxorubicin therapies are effective for those with the well-differentiated component. However, by using immune checkpoint inhibitors in combination with other conventional treatments, it may be possible to control the undifferentiated component and improve prognosis.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Idoso , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Carboplatina/uso terapêutico , Carcinoma/genética , Carcinoma/imunologia , Carcinoma/patologia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/imunologia , Carcinoma Endometrioide/patologia , Cisplatino/uso terapêutico , Reparo de Erro de Pareamento de DNA/efeitos dos fármacos , Doxorrubicina/uso terapêutico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/patologia , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Linfócitos do Interstício Tumoral , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/uso terapêutico , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia
14.
BMC Cancer ; 19(1): 748, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362708

RESUMO

BACKGROUND: Primary retroperitoneal serous adenocarcinoma (PRSA) is an extremely uncommon malignancy exclusively reported in females. Due to the rarity of the disease, it is difficult to establish a standardized treatment. CASE PRESENTATION: We describe a unique case of PRSA in a 71-year-old male who presented with right-sided lower back pain and numbness. Magnetic resonance imaging identified a mass invading the adjacent psoas muscle and twelfth rib. Tissue biopsy confirmed poorly differentiated PRSA. Patient was initially treated with neoadjuvant carboplatin and paclitaxel chemotherapy regimen. This resulted in complete radiological resolution of the tumor. However, 12 weeks later, rapid recurrence was noted on follow-up CT scan. The patient was then treated with external radiotherapy with concurrent nivolumab, an anti-PD-1 antibody. The patient displayed a positive response to treatment with reduction in primary tumor and metastases and had a sustained disease control. CONCLUSION: Treatment with radiotherapy in combination with anti-PD-1 antibody could be an effective modality of management for PRSA.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/terapia , Imunoterapia/métodos , Nivolumabe/uso terapêutico , Neoplasias Retroperitoneais/radioterapia , Neoplasias Retroperitoneais/terapia , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carboplatina/uso terapêutico , Cistadenocarcinoma Seroso/diagnóstico por imagem , Seguimentos , Humanos , Fatores Imunológicos/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Nivolumabe/farmacologia , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Neoplasias Retroperitoneais/diagnóstico por imagem , Resultado do Tratamento
15.
BMC Vet Res ; 15(1): 291, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409327

RESUMO

BACKGROUND: Oclacitinib is an orally bioavailable Janus Kinase (JAK) inhibitor approved for the treatment of canine atopic dermatitis. Aberrant JAK/ Signal Transducer and Activator of Transcription (STAT) signaling within hematologic and solid tumors has been implicated as a driver of tumor growth through effects on the local microenvironment, enhancing angiogenesis, immune suppression, among others. A combination of JAK/STAT inhibition with cytotoxic chemotherapy may therefore result in synergistic anti-cancer activity, however there is concern for enhanced toxicities. The purpose of this study was to evaluate the safety profile of oclacitinib given in combination with either carboplatin or doxorubicin in tumor-bearing dogs. RESULT: Oclacitinib was administered at the label dose of 0.4-0.6 mg/kg PO q12h in combination with either carboplatin at 250-300 mg/m2 or doxorubicin at 30 mg/m2 IV q21d. Nine dogs were enrolled in this pilot study (n = 4 carboplatin; n = 5 doxorubicin). No unexpected toxicities occurred, and the incidence of adverse events with combination therapy was not increased beyond that expected in dogs treated with single agent chemotherapy. Serious adverse events included one Grade 4 thrombocytopenia and one Grade 4 neutropenia. No objective responses were noted. CONCLUSIONS: Oclacitinib is well tolerated when given in combination with carboplatin or doxorubicin. Future work is needed to explore whether efficacy is enhanced in this setting.


Assuntos
Carboplatina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doxorrubicina/uso terapêutico , Neoplasias/veterinária , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carboplatina/administração & dosagem , Cães , Doxorrubicina/administração & dosagem , Quimioterapia Combinada , Feminino , Masculino , Neoplasias/tratamento farmacológico , Projetos Piloto , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem
16.
DNA Cell Biol ; 38(10): 1143-1146, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31464522

RESUMO

Cervical carcinoma is associated with high-risk human papillomavirus (HPV) DNA integration and usually occurs after age 21 (peak 45 years), as reflected in screening guidelines. Between 1999 and 2008, cervical carcinoma rate in adolescents aged 15-19 years was 0.15 per 100,000. HPV-negative cervical carcinoma is rare in adolescents. The youngest previously reported case was 15 years old. Treatment options for cervical carcinoma are limited after first-line therapy. Immune checkpoint inhibitors blocking programmed death receptor (PD-1) and its ligand, PD-L1, have shown objective clinical responses and are tolerable in adults with gynecologic cancers. This class of agents is well tolerated in pediatric patients. PD-1/PD-L1 is commonly expressed in gynecologic cancers but its expression may not predict clinical response. We describe an exceptional response to single agent nivolumab postradiation therapy in a 13-year-old adolescent with poorly differentiated cervical carcinoma and widespread metastatic disease.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Nivolumabe/uso terapêutico , Neoplasias do Colo do Útero/terapia , Adolescente , Carboplatina/uso terapêutico , Carcinoma/secundário , Carcinoma/cirurgia , Feminino , Raios gama/uso terapêutico , Humanos , Histerectomia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Excisão de Linfonodo , Ovariectomia , Paclitaxel/uso terapêutico , Papillomaviridae , Salpingectomia , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
17.
Acta Pharm ; 69(1): 87-97, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31259718

RESUMO

Despite growing prevalence of ovarian cancer (OC) in Pakistan, no literature evidence exists regarding its clinic-pathological characteristics, survival and compliance of patients with recurrent ovarian cancer on various chemo-protocols. An observational study was conducted by enrolling 251 recurrent OC patients on 7 different chemo-protocols, from a specialized cancer care hospital, Lahore, Pakistan, using convenient judgmental sampling. The study was conducted for a period of 6 months. Most of the patients were between 18 and 70 years of age, with IIIC FIGO stage and papillary serous histological grade. As per RECIST, improved partial response (PR) (63.3 %) and complete response (CR) (52.1 %) was observed in the CP (carboplatin + paclitaxel) arm, substantiated by improved median progression free survival (PFS) and overall survival (OS) in CP and CD (carboplatin + docetaxel) arms, respectively, yet with no significant differences in survival curves, PFS (p = 0.12) and OS (p = 0.22). Interestingly, the highest and the lowest patient non-compliance were observed in CG (carboplatin + gemcitabine) (81.6 %) and paclitaxel (4.5 %) arms, resp. As per the hazard model for survival, topotecan showed significant association with the therapy related events/deaths compared to other protocols. These data suggest that CP regimen exhibited improved clinical efficacy and decreased toxicity related non-compliance in recurrent ovarian cancer patients of Lahore.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adulto , Carboplatina/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Intervalo Livre de Progressão , Topotecan/administração & dosagem , Resultado do Tratamento , Adulto Jovem
18.
Can J Vet Res ; 83(3): 187-196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31308591

RESUMO

The proposed advantages of intra-arterial chemotherapy (IAC) are based on the premises of local dose escalation to the tumor and reduced availability of systemic drugs. There is a lack of objective pharmacokinetic data to confirm the advantage of IAC in dogs with naturally occurring urogenital tumors. The objective of this study was to determine if IAC administration in urogenital tumors would result in decreased systemic drug exposure when compared to intravenous routes. Twenty-two dogs with naturally occurring urogenital tumors were enrolled in this prospective case-controlled study. Mitoxantrone, doxorubicin, or carboplatin were administered by IAC and intravenous routes [intravenous awake (intravenous chemotherapy - IVC) and under general anesthesia (IVGAC)] 3 weeks apart. Serum assays were used to determine the extent of systemic drug exposure. Dose-normalized peak systemic serum concentration (Cmax) and area under the serum drug concentration-time curve (AUC) were used to quantify systemic exposure. A total of 26 mitoxantrone treatments were administered to 10 dogs. While there was no significant difference in Cmax, the AUC was significantly lower after IAC compared with IVGAC. Ten doxorubicin treatments were administered to 5 dogs. There were no significant differences in Cmax or AUC. A total of 14 carboplatin treatments were administered to 7 dogs. The Cmax was significantly lower for IAC compared to IVC, while the AUC values were equivocal. This study demonstrates certain lower serum values may be achieved after IAC delivery of carboplatin and mitoxantrone. These chemotherapy agents may have a preferred pharmacological profile for regional chemotherapy delivery in dogs with urogenital tumors.


Assuntos
Carboplatina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Injeções Intra-Arteriais/veterinária , Injeções Intravenosas/veterinária , Mitoxantrona/uso terapêutico , Neoplasias Urológicas/veterinária , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Área Sob a Curva , Carboplatina/administração & dosagem , Carboplatina/sangue , Carboplatina/farmacocinética , Cães , Feminino , Masculino , Mitoxantrona/administração & dosagem , Mitoxantrona/sangue , Mitoxantrona/farmacocinética , Projetos Piloto , Neoplasias Urológicas/tratamento farmacológico
19.
BMC Cancer ; 19(1): 693, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307410

RESUMO

BACKGROUND: To evaluate the safety and efficacy of intra-arterial chemotherapy (IAC) for the primary or secondary treatment of infants diagnosed with advanced retinoblastoma before 3 months of age. METHODS: This single-center retrospective study included 39 infants (42 eyes) aged ≤3 months who were diagnosed with unilateral or bilateral advanced intraocular retinoblastoma (group D and E eyes) and received IAC as primary or secondary treatment between June 2012 and February 2017. Based on each patient's therapeutic history and response to chemotherapeutic drugs, melphalan, topotecan, and/or carboplatin were used for IAC. The main outcomes included the technical success rate for IAC, survival rates, and adverse events. RESULTS: In total, 29 and 13 eyes received IAC as primary and secondary treatments, respectively. Catheterization was successful in 136 of 137 procedures. All eyes in the secondary IAC group had previously received intravenous chemotherapy. The mean number of IAC sessions for each eye was 3 (range, 2-6). The 2-year ocular survival rates were 80.7% (95% confidence interval [CI], 58.9-91.7) in the primary IAC group and 91.7% (95% CI, 53.9-98.8) in the secondary IAC group. During the follow-up period, 1 patient with unilateral disease (group E) developed extraocular disease and died. The 2-year recurrence-free survival rates in the primary and secondary IAC groups were 71.9% (95% CI, 49.4-85.7) and 75.0% (95% CI, 40.8-91.2), respectively. During each catheterization procedure, the main complications included eyelid erythema (2.4%), fundus hemorrhage (11.9%), myelosuppression (7.7%), transient vomiting and hair loss (2.6%), and transient pancytopenia (2.6%). Prolonged complications included phthisis bulbi (19.0%), vision loss (19.0%), poor vision (9.5%), and cataract (2.4%). There was no case of stroke, neurological impairment, secondary malignant tumor, or metastasis. CONCLUSIONS: Our findings suggest that IAC, whether primary or secondary, is effective and fairly safe for the management of advanced retinoblastoma in infants aged < 3 months. However, adverse events related to intra-arterial injection and the visual outcomes cannot be neglected and require further investigation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carboplatina/uso terapêutico , Etoposídeo/uso terapêutico , Infusões Intra-Arteriais/efeitos adversos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Vincristina/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/efeitos adversos , Cateterismo/efeitos adversos , Pré-Escolar , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias da Retina/mortalidade , Retinoblastoma/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/efeitos adversos
20.
Future Oncol ; 15(23): 2779-2790, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31293180

RESUMO

Aim: Platinum agents are DNA damaging agents with promising activity in breast cancers, especially in triple-negative subgroup. This meta-analysis was conducted to compare the treatments of platinum-based neoadjuvant chemotherapy (NAC) and standard NAC for triple-negative breast cancers (TNBCs). Materials & methods: Diverse electronic databases were searched to identify the randomized clinical trials that directly compared the treatments of platinum-based NAC versus NAC in TNBC patients. Toxicity of platinum-based regimens was further evaluated. Results: Addition of platinum agents significantly improved the pathological complete response rates in TNBC patients compared with the standard NAC. Unfortunately, platinum-based regimens were more likely to develop higher incidence of hematologic toxicities. Conclusion: Platinum-based NAC regimens could achieve significant pathological complete response improvement with well-tolerated toxicity in TNBC patients.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Neoadjuvante/métodos , Compostos de Platina/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Carboplatina/uso terapêutico , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Feminino , Humanos , Compostos de Platina/efeitos adversos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
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