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1.
J Surg Oncol ; 121(3): 447-455, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31919848

RESUMO

BACKGROUND: We aim to compare the clinical outcomes of patients with early-stage HER2+ breast cancer treated with adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC). METHODS: Patients with non-metastatic HER2+ breast cancer treated from 2009 to 2018 at our institution comprised our study cohort (n = 1254). Pathologic complete response (pCR) was defined as the absence of invasive disease in the breast and axilla after NAC. Log-rank, Kaplan-Meier, and inverse probability of treatment weighting were used to assess differences in disease-free and overall survival between groups stratified by AC vs. NAC and pCR vs. non-pCR. RESULTS: The majority received AC (n = 787 or 62.8%) while 467 (37.2%) patients received NAC. Median follow up for AC and NAC groups was 46 and 28 months, respectively. The crude disease-free survival and overall survival of our study cohort were 92.2% and 89.1% for AC, 89.1% and 82.2% for NAC pCR, and 68.1% and 60.0% for NAC non-pCR, respectively. For clinical stage ≥IIB patients, NAC conferred a positive but statistically nonsignificant treatment effect over AC in multivariate analysis. CONCLUSIONS: After adjusting for imbalances in our subgroups, we found that, regardless of the sequence of chemotherapy (AC vs. NAC), patients with early-stage HER2+ breast cancer had excellent outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante/mortalidade , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia/mortalidade , Receptor ErbB-2/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
2.
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
3.
Medicine (Baltimore) ; 98(52): e18513, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876741

RESUMO

BACKGROUND: This study evaluated the efficacy and safety of docetaxel combined with lobaplatin, relative to docetaxel combined with gemcitabine, for treating patients with recurrent metastatic breast cancer (rMBC). METHODS: Patients with rMBC received ≥2 cycles (21 days each) of either docetaxel and lobaplatin (DL; n = 21), or docetaxel and gemcitabine (DG; n = 22). On day 1 of each cycle, all patients were given 75 mg/m intravenous docetaxel. Patients in DL and DG were also given, respectively, 35 mg/m intravenous lobaplatin (day 2) or 1000 mg/m intravenous gemcitabine (days 1, 8). RESULTS: Five (11.6%) and 16 (37.2%) patients achieved complete remission and partial response, respectively; rates of response and disease control were 48.8%. The response rates of the groups were comparable (47.6%, 50.0%). The median survival times after relapse and metastasis of the DL group (18 months) were significantly less than that of the DG group (25 months). Median progression-free survivals after relapse and metastasis were similar (12 cf. 14 months). The main toxic side reaction was grade 2, with no treatment-related deaths. Rates of the following were comparable between DG and DL: grade 3 or 4 white blood cells (23.8%, 31.8%) and digestive tract toxicity (4.8%, 4.5%); neutropenia (28.6%, 22.7%); anemia (4.8%, nil); and thrombocytopenia (19.0%, 13.6%). Other toxicities included hepatic toxicity, myalgia, infection, and fatigue. CONCLUSIONS: Both the DL and DG regimens were associated with encouraging benefits, while treatment-related toxicity was manageable. Therefore, these regimens are effective options for treatment of rMBC. TRIAL REGISTRATION: This clinical trial study was approved by the Ethics Committee of Guizhou Cancer Hospital, and has been registered in the China Clinical Trial Center (December 8, 2014, No. ChiCTR-IPR-14005633).


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclobutanos/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ciclobutanos/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Docetaxel/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Projetos Piloto , Análise de Sobrevida
4.
Gynecol Oncol ; 155(3): 406-412, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31677820

RESUMO

OBJECTIVE: Increased Vascular Endothelial Growth Factor Receptor (VEGF) expression in endometrial cancer (EC) is associated with a poor prognosis. Preliminary clinical data reported Bevacizumab effectiveness in EC both as single agent and in combination with chemotherapy. METHODS: In a phase II trial, patients with advanced (FIGO stage III-IV) or recurrent EC were randomized to receive Carboplatin-Paclitaxel standard dose for 6-8 cycles vs Carboplatin-Paclitaxel and Bevacizumab 15 mg/kg in combination with chemotherapy and maintenance until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS). RESULTS: 108 patients were randomized; PFS (10.5 vs 13.7 months, HR 0.84 p = 0.43), overall response rate (ORR 53.1% vs 74.4%) and overall survival (OS) (29.7 vs 40.0 months, HR 0.71 p = 0.24) resulted in a non-significant increase in Bevacizumab treated patients. The PFS increase became significant when an exploratory analysis with the Breslow test was used. Moreover, patients treated with Bevacizumab experienced a significant increase in 6-month disease control rate (70.4% vs 90.7%). Cardiovascular events were more frequent in the experimental arm ("de novo" grade ≥2 hypertension 21% vs 0% and grade ≥2 thromboembolic events 11% vs 2% in the Bevacizumab vs standard treatment arm, respectively). CONCLUSIONS: Bevacizumab combined with chemotherapy in the treatment of advanced/recurrent EC failed to demonstrate a significant increase in PFS in the MITO END-2 trial. Nevertheless, these preliminary data suggests some effectiveness of the antiangiogenic agent which merits further exploration in a larger population with a better molecular characterization.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Intervalo Livre de Progressão , Estudos Prospectivos
5.
Jpn J Clin Oncol ; 49(8): 789-792, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31671191

RESUMO

A pilot study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer has been started in Korea. Archival tumor samples were tested for HRD and PD-L1 status. Treatment arms will be allocated according to the test results. For HRD+ patients, we tested the synergistic effects of olaparib and other agents; treatment arms will randomly be allocated. (Arm 1: olaparib and cediranib; Arm 2: olaparib and durvalumab). For HRD- patients, we tested the role of biomarker-driven immunotherapy according to PD-L1 expression (Arm 3: durvalumab and chemotherapy in patients with high PD-L1 expression; Arm 4: durvalumab, tremelimumab, and chemotherapy in patients with low PD-L1 expression). Sixty-eight patients will be included from three Korean institutions within 1 year. The primary endpoint is the response rate according to RECIST 1.1 (6 months after treatment initiation). This trial has been registered with clinicaltrials.gov, and the registration number is NCT03699449.


Assuntos
Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Terapia de Alvo Molecular , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Platina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Neoplasias Ovarianas/patologia , Projetos Piloto , República da Coreia
6.
N Engl J Med ; 381(20): 1929-1939, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31722153

RESUMO

BACKGROUND: Secondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation. METHODS: We randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel-carboplatin or gemcitabine-carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival. RESULTS: A total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P = 0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery. CONCLUSIONS: In this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Recidiva Local de Neoplasia/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Idoso , Bevacizumab/administração & dosagem , Carboplatina/administração & dosagem , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Paclitaxel/administração & dosagem , Qualidade de Vida , Reoperação , Análise de Sobrevida
7.
Lancet ; 394(10214): 2096-2107, 2019 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-31735560

RESUMO

BACKGROUND: Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. METHODS: We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged ≥75 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2-3 vs >3) and age (<75 years vs ≥75 years). Treatments were assigned based on a permuted blocked randomisation scheme with a block size of four. The isatuximab-pomalidomide-dexamethasone group received isatuximab intravenously on days 1, 8, 15, and 22 in the first 28-day cycle, then on days 1 and 15 in subsequent cycles. Both groups received oral pomalidomide on days 1 to 21 in each cycle, and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Dose reductions for adverse reactions were permitted for pomalidomide and dexamethasone, but not for isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, number NCT02990338. FINDINGS: Between Jan 10, 2017, and Feb 2, 2018, we randomly assigned 307 patients to treatment: 154 to isatuximab-pomalidomide-dexamethasone, and 153 to pomalidomide-dexamethasone. At a median follow-up of 11·6 months (IQR 10·1-13·9), median progression-free survival was 11·5 months (95% CI 8·9-13·9) in the isatuximab-pomalidomide-dexamethasone group versus 6·5 months (4·5-8·3) in the pomalidomide-dexamethasone group; hazard ratio 0·596, 95% CI 0·44-0·81; p=0·001 by stratified log-rank test. The most frequent treatment-emergent adverse events (any grade; isatuximab-pomalidomide-dexamethasone vs pomalidomide-dexamethasone) were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhoea (39 [26%] vs 29 [20%]). Adverse events with a fatal outcome were reported in 12 patients (8%) in the isatuximab-pomalidomide-dexamethasone group and 14 (9%) in the pomalidomide-dexamethasone group. Deaths due to treatment-related adverse events were reported for one patient (<1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection). INTERPRETATION: The addition of isatuximab to pomalidomide-dexamethasone significantly improves progression-free survival in patients with relapsed and refractory multiple myeloma. Isatuximab is an important new treatment option for the management of relapsed and refractory myeloma, particularly for patients who become refractory to lenalidomide and a proteasome inhibitor. FUNDING: Sanofi. VIDEO ABSTRACT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Ásia , Dexametasona/administração & dosagem , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Intervalo Livre de Progressão , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Resultado do Tratamento
9.
Crit Rev Oncol Hematol ; 143: 148-152, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31675543

RESUMO

Soluble PD-1 and PD-L1 are detected in the serum and plasma of lung cancer patients. The significance of these soluble proteins as prognostic or predictive markers in lung cancer is uncertain. The testing methods used to detect soluble PD1/PD-L1 are variable with no agreement on a common definition of a positive test. The advantages of validating soluble PD1/PD-L1 relevance in lung cancer include easiness of obtaining blood samples for testing, serial measurements to assess response to treatments such as immunotherapy, and potentially early identification of cancer relapse in cases treated with curative intent. In this review, we present the available data published on soluble PD1 and PD-L1 in lung cancer.


Assuntos
Antígeno B7-H1/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Receptor de Morte Celular Programada 1/sangue , Carcinoma de Pequenas Células do Pulmão/sangue , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Prognóstico , Receptor de Morte Celular Programada 1/imunologia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/imunologia
10.
Crit Rev Oncol Hematol ; 143: 130-138, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31634730

RESUMO

Germ cell tumors (GCTs) are the most common type of solid tumor amongst patients between 15 and 35 years of age. They are also one of the types of tumor with the highest cure rate, due to their high sensitivity to cisplatin based chemotherapy. Nonetheless, around 15-20% of metastatic patients will not have curative options after a relapse on the first and second line. This proves that new therapeutic options for these refractory GCTs patients need to be developed. This article offers a bibliographic review of all studies using targeted treatment or immunotherapy for refractory GCTs patients.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Humanos , Masculino , Terapia de Alvo Molecular , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Seminoma/tratamento farmacológico , Seminoma/patologia , Teratoma/tratamento farmacológico , Teratoma/patologia , Neoplasias Testiculares/patologia , Adulto Jovem
11.
Cancer Treat Rev ; 80: 101909, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629204

RESUMO

OBJECTIVE: This meta-analysis investigated the effectiveness of PARP inhibitors (PARPis) as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC), stratifying results based on BRCA mutational status into five different categories: whole population, germ-line BRCA mutated patients, somatic BRCA mutated patients, HRD patients and wild type population. METHODS: PubMed, Medline, Scopus, EMBASE and clinicaltrials.gov, as well as meeting proceedings were searched for eligible studies that described RCTs testing the efficacy of PARPis as maintenance treatment in platinum sensitive ROC. Data were extracted independently and analysed using RevMan statistical software version 5.3. Primary end-point was progression free survival (PFS). RESULTS: The analysis confirmed the positive effect of PARPis in patients with platinum sensitive ROC in case of germinal or somatic BRCA mutations. Specifically, HR for PFS was 0.26, 95% CI 0.21-0.31, p < 0.00001 for the mutation of BRCA gene and 0.24, 95%, CI 0.12-0.48, p < 0.0001 for the somatic alteration. In addition, in the HRD population, studies that analysed the efficacy of PARPis  reported a PFS improvement with HR 0.34, 95% CI 0.26-0.43, p < 0.00001. Finally, our analysis confirms the role of these drugs in prolonging PFS in the whole population with HR 0.36, 95% CI 0.32-0.42, p < 0.00001, although to a lesser extent, with a significant improvement even in wild type cancers with HR 0.49, 95%, CI 0.41-0.59, p < 0.00001). CONCLUSIONS: PARPis are effective regardless of BRCA mutational status. Future investigations are necessary to explore the use of different PARPis as monotherapy, comparing them among each other in terms of efficacy and toxicity, and exploring their potential re-use.


Assuntos
Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Feminino , Humanos , Quimioterapia de Manutenção , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Cancer Immunol Immunother ; 68(10): 1661-1669, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31606777

RESUMO

BACKGROUND: We previously found that PD-L1 expression is increased on tumor cells following vaccination treatments that lead to increased tumor-specific T cells that secrete IFNγ. Indoleamine 2,3-dioxygenase (IDO) is another IFNγ inducible gene that has potent immunosuppressive effects. There have been reports of IDO expression in prostate cancer; however, it is unknown whether IDO expression might similarly increase in prostate tumors following T-cell-based immunotherapy. METHODS: Blood samples from normal male blood donors (n = 12) and patients with different stages of prostate cancer (n = 89), including patients with metastatic, castration-resistant prostate cancer treated with a DNA vaccine and/or pembrolizumab, were evaluated for IDO activity by kynurenine and tryptophan levels. Metastatic tissue biopsies obtained pre- and post-treatments were evaluated for IDO expression. IDO suppression of vaccine-induced T-cell function was assessed by ELISPOT. RESULTS: Overall, IDO activity was increased in patients with more advanced prostate cancer. This activity, and IDO expression as detected immunohistochemically, increased following treatment with either a DNA vaccine encoding the prostatic acid phosphatase (PAP) tumor antigen or PD-1 blockade with pembrolizumab. Increased IDO activity after treatment was associated with the absence of clinical effect, as assessed by lack of PSA decline following treatment. Increased antigen-specific T-cell response, as measured by IFNγ release, to the vaccine target antigen was detected following in vitro stimulation of peripheral blood cells with 1-methyltryptophan. CONCLUSIONS: These findings suggest that IDO expression is a mechanism of immune evasion used by prostate cancer and that future clinical trials using T-cell-based immune strategies might best include IDO inhibition.


Assuntos
Vacinas Anticâncer/administração & dosagem , Imunoterapia , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Linfócitos T/efeitos dos fármacos
13.
Anticancer Res ; 39(10): 5653-5662, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570463

RESUMO

BACKGROUND/AIM: Factors influencing fulvestrant efficacy may be useful in selecting the optimal treatment regimen for postmenopausal Japanese women with metastatic/recurrent HR-positive, HER2-negative breast cancer. PATIENTS AND METHODS: We retrospectively evaluated progression-free and overall survival (PFS and OS) in 100 fulvestrant-treated patients according to metastatic site. RESULTS: Median PFS was significantly better in patients with non-visceral (bone and regional metastases; 22.8 months) vs. visceral metastasis (lung, liver, and other organs; 8.2 months; p=0.024), although median OS did not differ (p=0.922). Median PFS in patients with lung metastasis (20.8 months) and non-visceral metastasis (22.8 months) were comparable; patients with liver metastasis (6.1 months) and other organ metastases (3.7 months) had worse prognoses. CONCLUSION: Patients with non-visceral metastases had a better prognosis than those with visceral metastases. Fulvestrant induced a longer PFS in patients with non-visceral metastasis, and also in those with lung metastasis without liver or other organ involvement.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Fulvestranto/uso terapêutico , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/genética , Receptores de Superfície Celular/genética , Estudos Retrospectivos
14.
Anticancer Res ; 39(10): 5695-5701, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570469

RESUMO

Large tumor size and arterioportal shunt are poor prognostic factors for hepatocellular carcinoma. Lenvatinib is a novel and potent multi-tyrosine kinase inhibitor developed in Japan. A 66-year-old woman with hepatocellular carcinoma and untreated hepatitis C was referred to our hospital. She was judged as unresectable and was treated with four sessions of transarterial chemoembolization; however, the therapeutic effect was unsatisfactory because of major arterioportal shunt. Lenvatinib was sequentially administered for 4 months. Thereafter, we observed tumor shrinkage, complete disappearance of arterioportal shunt, and obvious improvement in liver function. A curative conversion hepatectomy was successfully accomplished. The extremely high levels of tumor markers almost normalized; the pretreatment levels were 1,008,021 ng/ml for alpha-fetoprotein. At 1 year after the primary treatment, the patient has not experienced recurrence. To our knowledge, this is the first case of a patient with initially unresectable hepatocellular carcinoma with arterioportal shunt who underwent conversion hepatectomy after multidisciplinary treatment, including lenvatinib.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , alfa-Fetoproteínas/metabolismo
15.
Anticancer Res ; 39(10): 5767-5772, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570480

RESUMO

BACKGROUND/AIM: To investigate the impact of inguinal lymph node dissection (ILND) following neoadjuvant chemoradiotherapy (NACRT) for rectal cancer patients with ILN metastasis. PATIENTS AND METHODS: Forty-three patients with rectal cancer underwent NACRT followed by curative surgery between January 2005 and December 2016. Seven patients underwent ILND after NACRT for clinically-positive ILN metastasis (ILND (+) group), while the remaining 36 did not receive ILND for clinically negative ILN metastasis (ILND (-) group). Their outcomes were retrospectively analyzed. RESULTS: Only one patient in the ILND (+) group had a local recurrence at six years after surgery. The 5-year recurrence-free survival was 100% and 65.4% in the ILND (+) and ILND (-) groups, respectively (p=0.09), and the 5-year overall survival was 100% and 83.2%, respectively (p=0.32). CONCLUSION: ILND following NACRT seems effective for rectal cancer patients with ILN metastasis.


Assuntos
Canal Inguinal/patologia , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adulto , Idoso , Biópsia/métodos , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/patologia , Estudos Retrospectivos
16.
Medicine (Baltimore) ; 98(38): e16988, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567935

RESUMO

RATIONALE: Peripherally inserted central catheters (PICC), normally located at the lower 1/3rd of the superior vena cava (SVC) and cavo-atrial junction, are commonly used in cancer patients. Persistent left superior vena cava (PLSVC) is a vascular anomaly, in patients with which seldom research was reported about PICC implanted. After obtaining written informed consent, we present a case where two successful insertions of PICC were performed in a 50-year-old female patient with PLSVC and right SVC. PATIENTS CONCERNS: The patient had ovarian cancer and was admitted for chemotherapy using PICC. DIAGNOSES: Ovarian cancer and PLSVC. INTERVENTIONS AND OUTCOMES: Following insertion of PICC in PLSVC, thrombosis developed. PICC was removed after routine anticoagulation therapy. Owing to tumor recurrence, a second PICC was inserted in the right SVC without any complications. LESSONS: PICC insertion in PLSVC for chemotherapy may be associated with an increased risk of deep venous thrombosis of the upper extremity. A right catheter insertion in patient with PLSVC was preferred.


Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Malformações Vasculares/complicações , Veia Cava Superior/anormalidades , Trombose Venosa/diagnóstico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Braço , Cateterismo Periférico/efeitos adversos , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Neoplasias Ovarianas/complicações , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia
17.
Gynecol Oncol ; 155(3): 530-537, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31604664

RESUMO

INTRODUCTION: More than 80 % of women with advanced ovarian cancer relapse either during or after adjuvant therapy. Platinum-sensitive women are rechallenged with a platinum-combination therapy and platinum-resistant women are challenged with non-platinum drugs. Gemcitabine is one of many treatments that can be used both as single-agent or as combination therapy for the treatment of recurrent ovarian cancer. METHODS: We included all randomised controlled trials investigating patients treated with gemcitabine for recurrent ovarian cancer and reporting data on overall survival, progression-free survival and toxicity. CENTRAL, EMBASE and MEDLINE were searched on the 31st of May 2019. RESULTS: We included six randomised controlled trials that evaluated gemcitabine either alone or as combination therapy. Two studies compared gemcitabine to pegylated liposomal doxorubicin in women with platinum-resistant recurrent ovarian cancer. Difference in overall and progression-free survival was non-significant. Gemcitabine treatment was associated with significantly more neutropenia, whereas pegylated liposomal doxorubicin was associated with significantly more hand-foot syndrome. One study evaluated carboplatin and gemcitabine to carboplatin. Difference in overall survival was non-significant, but progression-free survival was longer with gemcitabine and carboplatin (HR: 0.72, 95% CI 0.58-0.9). One study evaluated gemcitabine with gemcitabine and pertuzumab. Overall survival and progression-free survival was similar between the two arms. One study compared gemcitabine and carboplatin to gemcitabine, carboplatin and bevacizumab. Overall survival was similar in the two arms. Progression-free survival was significantly better in the bevacizumab arm (HR 0.48 95% CI 0.39-0.61). One study compared etoposide and gemcitabine to etoposide. The study showed similar overall survival and progression-free survival. DISCUSSION: The results show that gemcitabine is an active and safe agent in the treatment of both platinum-sensitive and resistant recurrent ovarian cancer but might highlight the need of new randomised studies in heavily pre-treated patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Int J Radiat Oncol Biol Phys ; 105(3): 471-472, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31540590
19.
J Cancer Res Clin Oncol ; 145(12): 3067-3073, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31563974

RESUMO

BACKGROUND: The combination of dexamethasone, high-dose cytarabine, and cisplatin (DHAP) is an established salvage regimen for lymphoma patients. We hypothesized that a modified administration schedule for cisplatin and cytarabine results in lower toxicity and improved efficacy. METHODS: We retrospectively analysed 119 patients with relapsed or refractory, aggressive, or indolent B-cell lymphomas, mantle-cell lymphomas, peripheral T-cell lymphomas, or Hodgkin's lymphomas who were treated with the modified DHAP (mDHAP) regimen (dexamethasone 40 mg 15 min-i.v. infusion, days 1-4; cytarabine 2 × 0.5 g/m2 1 h-i.v. infusion, days 1-4; cisplatin 25 mg/m2 24 h-i.v. infusion, days 1-4). Responding and eligible patients underwent stem-cell transplantation. RESULTS: In total, 185 treatment cycles were evaluable. Severe myelosuppression was the main toxicity occurring in 90% of the cycles. Febrile neutropenia or documented infection was found in less than 40%. Two patients died related to treatment (TRM, 1.7%). Nephrotoxicity did not exceed CTC grade 3, which occurred in four cycles only (2.2%). Complete (CR) or partial (PR) responses after mDHAP were documented in 16% and 39% (overall response rate 55%). Harvest of autologous stem cells was successful in 94 (79%) patients and 85 patients (71%) proceeded to stem-cell transplantation. The median overall and progression-free survival was 50.8 and 25.8 months. CONCLUSIONS: An improvement in efficacy could not be observed after modified DHAP regimen; however, manageable toxicity and reduced renal complications suggest further investigation. The study, however, also underlines the need for new concepts in the management of advanced and high-risk lymphomas.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Idoso , Cisplatino/uso terapêutico , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia de Salvação/métodos , Adulto Jovem
20.
Future Oncol ; 15(24s): 3-6, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31385526

RESUMO

We report a case of a 37-year-old man with metastatic differentiated thyroid carcinoma, previously submitted to total thyroidectomy, radio-iodine therapy and lung metastasectomy, who underwent systemic treatment with lenvatinib for tumor recurrence in the lung, mediastinal lymph nodes, left gluteus and left orbit. Lenvatinib induced rapid and durable disease regression; the drug effect has continued after >1 year, as well as a very considerable clinical benefit. The results achieved by lenvatinib in treatment of metastatic differentiated thyroid carcinoma are clear and irrefutable. Real-life data, obtained by case reports and retrospective studies, are equally important to increase the knowledge about this drug and improve the clinical management.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Terapia Combinada , Humanos , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/efeitos adversos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Metastasectomia , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
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