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1.
Medicine (Baltimore) ; 100(12): e25264, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761726

RESUMO

RATIONALE: Primary peritoneal epithelioid mesothelioma of clear cell type is an extremely rare entity composed of clear cytoplasm. It is challenging to diagnose because of the morphological resemblance to clear cell tumor. PATIENTS CONCERNS: A 69-year-old male patient had swollen lymph nodes in the right inguinal region for 7 months and was constipated for 1 month. DIAGNOSIS: The patient was diagnosed as peritoneal epithelioid mesothelioma of clear cell type based on computed tomography scan, pathology, immunohistochemistry, special staining and whole-exome sequencing. This patient harbored VHL gene alteration in exon 1 and homologous recombination defect (with a score of 45). This finding indicated that this patient might be sensitive to platinum-based therapy and Poly ADP-ribose Polymerase (PARP) inhibitor. This patient carried no microsatellite instability, a low level of tumor mutation burden, and a high extent of intratumoral heterogeneity. Eighteen neoantigens were detected. INTERVENTIONS: The patient received surgery-based multidisciplinary treatment by integrating cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was administered with docetaxel 120 mg plus cisplatin 120 mg, at 43°C, for 60 minutes. After operation, the patient received intravenous (IV) chemotherapy with docetaxel 60 mg, pemetrexed 750 mg and cisplatin 100 mg, and then intraperitoneal (IP) chemotherapy with docetaxel 40 mg. The patient received interventional therapy of hepatic artery embolization for 5 times. OUTCOMES: Regular follow-up was performed until Oct 14, 2020. The patient died 31.6 months later owing to incomplete intestinal obstruction. LESSONS: Primary peritoneal epithelioid mesothelioma of clear cell type needs to be differentiated from a variety of clear cell tumors. This disease is characterized by specific genetic alteration. Whole-exome sequencing contributes to guide individualized therapy. CRS-HIPEC helps achieve long-term overall survival.


Assuntos
Cisplatino/administração & dosagem , Procedimentos Cirúrgicos de Citorredução/métodos , Docetaxel/administração & dosagem , Pemetrexede/administração & dosagem , Neoplasias Peritoneais , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Idoso , Antineoplásicos/administração & dosagem , Embolização Terapêutica/métodos , Humanos , Imuno-Histoquímica , Masculino , /patologia , /terapia , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/fisiopatologia , Neoplasias Peritoneais/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Sequenciamento Completo do Exoma/métodos
2.
Lancet Respir Med ; 9(3): 305-314, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33347829

RESUMO

BACKGROUND: Immunotherapy combined with chemotherapy has been shown to be efficacious as treatment for advanced non-squamous non-small-cell lung cancer (NSCLC) without targetable genetic aberrations; however, there is scarce evidence of the effectiveness of the combinations in the Asian population. We evaluated camrelizumab plus chemotherapy against non-squamous NSCLC in China. METHODS: We did a randomised, open-label, multicentre, phase 3 trial (CameL) in 52 hospitals in China for patients with non-squamous NSCLC without EGFR and ALK alteration. Eligible patients were aged 18-70 years and had no previous systemic chemotherapy, Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (version 1.1). Patients were randomly assigned (1:1) to receive 4-6 cycles of carboplatin (area under curve 5 mg/mL per min) plus pemetrexed (500 mg/m2) with or without camrelizumab (200 mg) every 3 weeks, followed by maintenance therapy with camrelizumab plus pemetrexed or pemetrexed alone. Medication was administered intravenously on day 1 of each 3-week treatment cycle. Randomisation was done using a centralised interactive web-response system with the block size randomly generated as four or six and stratified by sex and smoking history. The two primary endpoints were progression-free survival per blinded independent central review, in all patients and in patients who were PD-L1 positive. Primary analysis was done in the full analysis set that included all randomly assigned patients who received at least one dose of the study treatment. Herein, due to the primary endpoint being met at the interim analysis, we reported the findings of prespecified interim analysis, which only included confirmatory statistical testing for progression-free survival in all patients. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT03134872 (follow-up is ongoing). FINDINGS: Between May 12, 2017, and June 6, 2018, of the 419 patients who were randomly assigned, seven did not receive assigned treatment and 412 received either camrelizumab plus chemotherapy (n=205) or chemotherapy alone (n=207). At interim analysis, median follow-up duration was 11·9 months (IQR 9·0-14·9). Progression-free survival in this interim analysis was significantly prolonged with camrelizumab plus chemotherapy than with chemotherapy alone (median 11·3 months [95% CI 9·6-15·4] vs 8·3 months [6·0-9·7]; hazard ratio 0·60 [0·45-0·79]; one-sided p=0·0001). Most common grade 3 or worse treatment-related adverse events were decreased neutrophil count (78 [38%] patients in the camrelizumab plus chemotherapy group vs 63 [30%] patients in the chemotherapy alone group), decreased white blood cell count (40 [20%] vs 30 [14%]), anaemia (38 [19%] vs 23 [11%]), and decreased platelet count (34 [17%] vs 24 [12%]). Serious treatment-related adverse events occurred in 74 (36%) patients in the camrelizumab plus chemotherapy group and 27 (13%) patients in the chemotherapy alone group. INTERPRETATION: The primary endpoint was met at the interim analysis, showing a statistically significant and clinically meaningful improvement in progression-free survival with camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in all patients, supporting camrelizumab plus carboplatin and pemetrexed as a first-line treatment option for Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations. The trial is being continued to collect long-term outcomes in all patients and carry out confirmatory statistical testing for progression-free survival in the PD-L1-positive population. FUNDING: Jiangsu Hengrui Medicine.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/administração & dosagem , Administração Intravenosa , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Método Simples-Cego
3.
Lancet Oncol ; 21(9): 1213-1223, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32888453

RESUMO

BACKGROUND: There is a strong unmet need to improve systemic therapy in mesothelioma. Chemotherapy with cisplatin and pemetrexed improves survival in malignant pleural mesothelioma, and immune checkpoint inhibitors are an emerging treatment in this disease. We aimed to evaluate the activity of durvalumab, an anti-PD-L1 antibody, given during and after first-line chemotherapy with cisplatin and pemetrexed in patients with advanced malignant pleural mesothelioma. METHODS: DREAM was a multicentre, single-arm, open-label, phase 2 trial done in nine hospitals in Australia. Eligible patients were aged 18 years or older and had histologically confirmed malignant pleural mesothelioma considered unsuitable for cancer-directed surgery, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease as per the modified Response Evaluation Criteria in Solid Tumors version 1.0 (mRECIST) for mesothelioma that was previously untreated with systemic therapy. All histological subtypes were eligible. The first six participants were treated for two cycles in a safety run-in. All participants received cisplatin 75 mg/m2, pemetrexed 500 mg/m2, and durvalumab 1125 mg intravenously on day 1 of a 3-weekly schedule for a maximum of six cycles. Change from cisplatin to carboplatin with an area under the curve of 5 was permitted. Durvalumab was continued for a maximum of 12 months. The primary endpoint was progression-free survival at 6 months, measured according to mRECIST for malignant pleural mesothelioma and analysed in the intention-to-treat population. Safety analyses included all participants who receive at least one dose of any study drug. This study is registered with the Australia New Zealand Clinical Trials Registry, ACTRN12616001170415. FINDINGS: Between Dec 28, 2016, and Sept 27, 2017, 55 participants were enrolled. 54 patients were eligible and were followed up for a median of 28·2 months (IQR 26·5-30·2). 31 (57%; 95% CI 44-70) of 54 patients were alive and progression-free at 6 months. The most common grade 3-4 adverse events were neutropenia (seven [13%] patients), nausea (six [11%]), and anaemia (four [7%]). A total of 60 serious adverse events occurred in 29 participants, five of which were considered possibly related to durvalumab. Five patients died during the study treatment; none of these five deaths were attributed to study treatment. INTERPRETATION: The combination of durvalumab, cisplatin, and pemetrexed has promising activity and an acceptable safety profile that warrants further investigation in a randomised phase 3 trial. FUNDING: AstraZeneca.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Pemetrexede/administração & dosagem , Neoplasias Pleurais/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Anti-Idiotípicos/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Austrália/epidemiologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/genética , Cisplatino/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/genética , Mesotelioma/imunologia , Mesotelioma/patologia , Pessoa de Meia-Idade , Pemetrexede/efeitos adversos , Neoplasias Pleurais/genética , Neoplasias Pleurais/imunologia , Neoplasias Pleurais/patologia , Intervalo Livre de Progressão
4.
Anticancer Res ; 40(8): 4245-4251, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727751

RESUMO

BACKGROUND: Organic cation transporter 6 (OCT6) encoded by solute carrier family 22 member 16 (SLC22A16) is involved in regulating cellular sensitivity and resistance to platinum derivatives. SLC22A16 has functional genetic variants but the association between these variants and the effectiveness of antitumor drugs remains unexplored. PATIENTS AND METHODS: This study retrospectively analyzed data from 160 patients with advanced non-small cell lung cancer treated with platinum-based combination chemotherapy for first-line chemotherapy between October 2010 and May 2018. We investigated the association between the genetic variant of SLC22A16 and clinical outcomes. RESULTS: Patients with the rs714368 GG genotype had a shorter progression-free survival than those with AA or AG. Gene polymorphism was not associated with adverse effects. The predictive effect of rs714368 was confirmed in multivariate analysis using a Cox proportional hazards model. CONCLUSION: A genetic variant of SLC22A16 is a potential predictive biomarker for response to platinum-based chemotherapy for non-small cell lung cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
5.
AAPS PharmSciTech ; 21(5): 193, 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32661922

RESUMO

Pemetrexed disodium (PMX) stands out in the treatment of non-small cell lung cancer (NSCLC), but with short half-life and toxic side effects. This study was to design cationic liposomes for targeting delivery PMX to the lungs. The PMX cationic liposome was prepared by thin-film hydration using stearylamine (SA) as the positive component of charge-regulating charge. Then, the PMX cationic liposome (SA-PMX-Lips) was characterized by particle size, morphology, entrapment efficiency (EE), and drug loading (DL). Finally, the drug release behavior in vitro, the pharmacokinetic study, and tissue distribution of SA-PMX-Lips were evaluated separately, with PMX solution (PMX-Sol) and PMX liposome (PMX-Lips) as the control. According to results, SA-PMX-Lips were spherical and the particle size was 219.7 ± 4.97 nm with a narrow polydispersity index (PDI) (0.231 ± 0.024) and a positive zeta potential 22.2 ± 0.52 mV. Its EE was 92.39 ± 1.94% and DL was 9.15 ± 0.07%. The results of in vitro and in vivo experiments showed that SA-PMX-Lips released slowly, prolonged retention time and increased the value of AUC. More notably, SA-PMX-Lips could improve the accumulation of drugs in the lungs and the relative uptake rate (Re) was 2.35 in the lungs, which indicated its lung targeting. In summary, SA-PMX-Lips showed the potential for the effective delivery of PMX and the treatment of NSCLC.


Assuntos
Aminas/química , Pemetrexede/administração & dosagem , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Liberação Controlada de Fármacos , Humanos , Lipossomos , Neoplasias Pulmonares/tratamento farmacológico , Tamanho da Partícula , Pemetrexede/farmacocinética , Pemetrexede/uso terapêutico , Distribuição Tecidual
6.
Medicine (Baltimore) ; 99(22): e19956, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481365

RESUMO

RATIONALE: Malignant peritoneal mesothelioma is a rare tumor with a poor prognosis and has no recommended therapy after first-line pemetrexed and platinum-based chemotherapy. Moreover, effects of immune checkpoint inhibitors on peritoneal mesothelioma remains to be elucidated. We herein report the case of a 75-year-old man with peritoneal mesothelioma treated with cisplatin plus pemetrexed and subsequent nivolumab. PATIENT CONCERNS: A 75-year-old man was referred to our hospital due to lower abdominal pain. DIAGNOSIS: Positron emission tomography-computed tomography (CT) showed the accumulation of fluorodeoxyglucose in an intraperitoneal mass. A histological examination of a laparoscopic biopsy specimen revealed malignant peritoneal mesothelioma. INTERVENTIONS: After 4 cycles of cisplatin plus pemetrexed and 13 subsequent cycles of pemetrexed maintenance therapy showed beneficial responses until CT revealed liver metastasis. Nivolumab was then administered as the second-line therapy. OUTCOMES: After 3 cycles of biweekly nivolumab administration, he developed severe abdominal distention. CT revealed an intraperitoneal mass growing much more rapidly than ever, indicating hyperprogressive disease after nivolumab treatment. He ultimately died 51 days after the initial nivolumab administration. LESSONS: To our knowledge, this is the first report of hyperprogressive disease in a case of peritoneal mesothelioma after nivolumab treatment. While immune checkpoint inhibitors may be promising therapeutic strategies for treating malignant peritoneal mesothelioma, careful monitoring must be practiced with their application.


Assuntos
Antineoplásicos/administração & dosagem , Mesotelioma/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/administração & dosagem , Humanos , Masculino , Mesotelioma/diagnóstico por imagem , Nivolumabe/administração & dosagem , Pemetrexede/administração & dosagem , Neoplasias Peritoneais/diagnóstico por imagem
7.
J Cancer Res Ther ; 16(2): 222-229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474505

RESUMO

Aims: The aim of this study is to investigate patients with unresectable Stage III non-small-cell lung cancer (NSCLC) receiving radiotherapy with induction and concurrent pemetrexed or docetaxel plus cisplatin (PP/DP) chemotherapy and to identify the subgroup most likely to benefit from induction chemotherapy (IC). Subjects and Methods: Patients with unresectable measurable Stage III NSCLC received two cycles of PP/DP IC followed by concurrent chemoradiotherapy at a dose of 60-66 Gy. Statistical Analysis Used: Cox regression analysis was performed to evaluate the prognostic factors for survival; logistic regression analysis was used to evaluate the predictors for response to IC, and the receiver operating characteristic curves were used to evaluate the independent factors predicting response. Results: Eighty patients were included; the median survival time (MST) was 22.1 months. Partial response (PR) to IC was an independent prognostic factor for overall survival. For patients in the PR and stable disease groups, the MST was 36.7 and 19.5 months, respectively. The independent predictors of PR to IC included classification as stage N3 cancer, baseline carcinoembryonic antigen (CEA) levels >10 ng/ml, and cytokeratin fragment 19 (CYFRA21-1) levels >6 ng/ml. With each additional independent predictor, the likelihood of having have PR to IC increased. Conclusions: Radiotherapy with induction and concurrent PP/DP chemotherapy is feasible for patients with unresectable Stage III NSCLC. IC may improve the survival of IC responders, as predicted by elevated CEA and CYFRA21-1 levels and classification as stage N3 cancer. Additional randomized trials on IC may consider these predictors to tailor individualized treatments.


Assuntos
Antígenos de Neoplasias/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno Carcinoembrionário/sangue , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Quimiorradioterapia/mortalidade , Quimioterapia de Indução/mortalidade , Queratina-19/sangue , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Curva ROC , Taxa de Sobrevida
8.
Cancer Sci ; 111(6): 1933-1942, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32277531

RESUMO

Combination antiprogrammed death 1/programmed death-ligand 1 Ab and platinum-based chemotherapy is standard first-line treatment for advanced non-small-cell lung cancer without targetable oncogene alterations. We describe the long-term safety and efficacy data from a previously reported phase Ib study of nivolumab and chemotherapy. Japanese patients with non-small-cell lung cancer were assigned to a treatment arm based on histology and treatment history. Nivolumab (10 mg/kg, i.v.) and chemotherapy (4 arms) were given every 3 weeks: arm A, 4 cycles of cisplatin and gemcitabine (first-line); arm B, 4 cycles of cisplatin and pemetrexed followed by pemetrexed maintenance therapy (first-line); arm C, 4-6 cycles of carboplatin, paclitaxel, and bevacizumab followed by bevacizumab (first-line); and arm D, docetaxel (second- or third-line). Study treatments were continued every 3 weeks as maintenance therapy until disease progression. Minimum follow-up period was 57.9 months. Median progression-free survival (median [range, plus sign indicates censored data]) was 6.3 (0.7+-47.8), 11.8 (1.4-65.1+), 40.7 (5.3-60.8+), and 3.2 (1.9-10.9) months, and 5-year progression-free survival was observed in 0/6, 1/6, 1/6, and 0/6 patients in arms A, B, C, and D, respectively. Median overall survival was 13.2 (11.0-55.4), 28.5 (14.6-66.2+), not reached (24.2-67.4+), and 12.5 (9.8-16.9) months; the number of patients surviving 5 years were 0/6, 1/6, 4/6, and 0/6 in arms A, B, C, and D, respectively. No unexpected severe adverse events or treatment-related deaths occurred. Nivolumab and platinum-based chemotherapy combinations showed long-term tolerability. A moderate proportion of patients in arm C showed 5-year progression-free and overall survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Intervalo Livre de Progressão , Resultado do Tratamento
9.
Dermatol Online J ; 26(2)2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32239889

RESUMO

Transient acantholytic dermatosis (TAD) is a relatively common entity that has been also noted to occur in patients with cancer. Herein, we describe a case of transient acantholytic dermatosis occurring in a patient with a history of prostate cancer status post radiation, now being treated with combination therapy with pembrolizumab and carboplatin-pemetrexed for advanced lung adenocarcinoma. Our case emphasizes the importance of being cognizant of TAD and its associations, particularly in cancer patients.


Assuntos
Acantólise/etiologia , Adenocarcinoma/complicações , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ictiose/etiologia , Neoplasias Pulmonares/complicações , Acantólise/patologia , Adenocarcinoma/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Diagnóstico Diferencial , Humanos , Ictiose/patologia , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pemetrexede/administração & dosagem , Neoplasias da Próstata/complicações , Neoplasias da Próstata/radioterapia , Pele/patologia
10.
Respir Investig ; 58(4): 269-274, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32111518

RESUMO

BACKGROUND: Carboplatin plus nanoparticle albumin-bound paclitaxel (nab-PTX) is one of the available first-line treatments for non-small cell lung cancer (NSCLC) patients. However, the efficacy of carboplatin plus nab-PTX as second-line, remains unknown. We examined the efficacy of carboplatin plus nab-PTX after cisplatin plus pemetrexed in non-squamous NSCLC patients. METHODS: We retrospectively reviewed advanced non-squamous NSCLC patients who received carboplatin plus nab-PTX as a second-line chemotherapy regimen after cisplatin plus pemetrexed in our hospital between March 2013 and December 2017. We assessed clinical characteristics, efficacy, and toxicities. RESULTS: Forty-four patients were recruited. The overall response rate (ORR) was 29% and the disease control rate (DCR), 69%. The median progression-free survival (mPFS) was 3.7 months (95% CI: 2.4-5.5 months) and the median overall survival, 16.6 months (95% CI:8.8-19.5 months). We assessed the ORR and mPFS using the best overall response in the prior regimen. The ORR and mPFS were better in the PD group (ORR; 44% and mPFS: 5.6 months). CONCLUSIONS: Carboplatin plus nab-PTX after cisplatin plus pemetrexed in non-squamous NSCLC patients is a treatment option. There were several cases where cisplatin plus pemetrexed was not effective, but Carboplatin plus nab-PTX was.


Assuntos
Paclitaxel Ligado a Albumina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Adulto , Idoso , Paclitaxel Ligado a Albumina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Cisplatino/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/efeitos adversos , Pemetrexede/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
11.
Eur Radiol ; 30(5): 2692-2702, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32020400

RESUMO

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.


Assuntos
Adenocarcinoma de Pulmão/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Micro-Ondas/uso terapêutico , Recidiva Local de Neoplasia/terapia , Ablação por Radiofrequência/métodos , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Compostos Organoplatínicos/administração & dosagem , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Intervalo Livre de Progressão , Estudos Prospectivos , Resultado do Tratamento , Vinorelbina/administração & dosagem
12.
Lancet Oncol ; 21(3): 387-397, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32035514

RESUMO

BACKGROUND: Pembrolizumab plus pemetrexed-platinum led to superior overall survival and progression-free survival, and a higher proportion of patients with a confirmed complete or partial response over placebo plus pemetrexed-platinum in the KEYNOTE-189 study. We aimed to evaluate prespecified exploratory patient-reported outcomes (PROs) in patients in KEYNOTE-189. METHODS: In the multicentre, double-blind, randomised, placebo-controlled, phase 3 KEYNOTE-189 study done at 126 cancer centres in 16 countries, eligible patients aged 18 years or older with histologically or cytologically confirmed metastatic non-squamous non-small-cell lung cancer without sensitising EGFR or ALK alterations, measurable disease as per Response Evaluation Criteria in Solid Tumors (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1 were enrolled. Patients were randomly assigned (2:1) to receive intravenous pembrolizumab (200 mg) or saline placebo every 3 weeks for up to 2 years (35 cycles); all patients received four cycles of intravenous pemetrexed (500 mg/m2) with carboplatin (5 mg/mL per min) or cisplatin (75 mg/m2; investigator's choice) every 3 weeks for four cycles, followed by pemetrexed maintenance therapy every 3 weeks. Permuted block randomisation (block size six) was done with an interactive voice-response system and stratified by PD-L1 expression, choice of platinum, and smoking status. Patients, investigators, and other study personnel were unaware of treatment assignment. The European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) and Lung Cancer 13 (QLQ-LC13) were administered at cycles 1-5, every three cycles thereafter during year 1, and every four cycles during years 2-3. The primary endpoints (overall survival and progression-free survival) have been published previously. Key PRO endpoints were change from baseline to week 12 (during chemotherapy) and week 21 (following chemotherapy) in QLQ-C30 global health status/quality of life (GHS/QOL) score, and time to deterioration in cough, chest pain, or dyspnoea. PROs were analysed in all randomly assigned patients who received at least one dose of study medication and who completed at least one PRO assessment, and the results are provided with two-sided, nominal p values. This ongoing study is registered with ClinicalTrials.gov, number NCT02578680. FINDINGS: Between Feb 26, 2016, and March 6, 2017, 616 patients were enrolled; median follow-up was 10·5 months (range 0·2-20·4) as of data cutoff on Nov 8, 2017. 402 (99%) of 405 patients in the pembrolizumab plus pemetrexed-platinum group and 200 (99%) of 202 patients in the placebo plus pemetrexed-platinum-treated group completed at least one PRO assessment. At baseline, 359 (89%) of 402 patients in the pembrolizumab plus pemetrexed-platinum group and 180 (90%) of 200 in the placebo plus pemetrexed-platinum group were compliant with QLQ-C30; at week 12, 319 (90%) of 354 and 149 (89%) of 167 patients were compliant, respectively; and at week 21, 249 (76%) of 326 and 91 (64%) of 143 patients were compliant, respectively. From baseline to week 12, GHS/QOL scores were maintained with both pembrolizumab plus pemetrexed-platinum (least-squares mean change: 1·0 point [95% CI -1·3 to 3·2] increase) and placebo plus pemetrexed-platinum (-2·6 points [-5·8 to 0·5] decrease; between-group difference: 3·6 points [-0·1 to 7·2]; p=0·053). From baseline to week 21, GHS/QOL scores were better maintained with pembrolizumab plus pemetrexed-platinum (least-squares mean change: 1·3 points [95% CI -1·2 to 3·6] increase) than with placebo plus pemetrexed-platinum (-4·0 points [-7·7 to -0·3] decrease; between-group difference: 5·3 points [1·1 to 9·5]; p=0·014). Median time to deterioration in cough, chest pain, or dyspnoea was not reached (95% CI 10·2 months to not reached) with pembrolizumab plus pemetrexed-platinum, and was 7·0 months (4·8 months to not reached) with placebo plus pemetrexed-platinum (hazard ratio 0·81 [95% CI 0·60-1·09], p=0·16). INTERPRETATION: The addition of pembrolizumab to standard chemotherapy maintained GHS/QOL, with improved GHS/QOL scores at week 21 in the pembrolizumab plus chemotherapy group compared with the placebo plus chemotherapy group. These data further support use of pembrolizumab plus pemetrexed-platinum as first-line therapy for patients with metastatic non-squamous non-small-cell lung cancer. FUNDING: Merck Sharp & Dohme.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Adenocarcinoma de Pulmão/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pemetrexede/administração & dosagem , Prognóstico , Taxa de Sobrevida , Adulto Jovem
13.
Sci Rep ; 10(1): 843, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965001

RESUMO

To investigate the predictive value of methylthioadenosine phosphorylase (MTAP) on treatment response and survival in advanced lung adenocarcinoma. MTAP expression was detected by immunohistochemistry. Treatment response and survival were compared according to MTAP expression level. The results indicated MTAP-low expression was observed in 61.2% (101/165) of all patients. The objective response rate and disease control rate improved in the MTAP-low group (64.4% vs 46.9%, p = 0.035; 92.1% vs. 79.7%, p = 0.03; respectively). The median progression-free survival and survival time in the MTAP-low group were significantly lower than that in the MTAP-high group (8.1 vs. 13.1 months, p = 0.002; 22 vs. 32 months, p = 0.044). Multivariate analysis demonstrated that brain metastasis (HR 1.55, p = 0.046), thoracic radiation (HR 0.52, p = 0.026), and MTAP-low expression (HR 1.36, p = 0.038) were independent factors on survival. It is concluded that MTAP-low expression could predict improved treatment response but worsened survival in advanced lung adenocarcinoma.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Expressão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede/administração & dosagem , Compostos de Platina/administração & dosagem , Purina-Núcleosídeo Fosforilase/deficiência , Purina-Núcleosídeo Fosforilase/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Feminino , Previsões , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Purina-Núcleosídeo Fosforilase/genética , Taxa de Sobrevida , Resultado do Tratamento
14.
J Clin Oncol ; 38(2): 115-123, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31682542

RESUMO

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor combined with cytotoxic chemotherapy is highly effective for the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations; however, little is known about the efficacy and safety of this combination compared with that of standard therapy with EGFR- tyrosine kinase inhibitors alone. METHODS: We randomly assigned 345 patients with newly diagnosed metastatic NSCLC with EGFR mutations to gefitinib combined with carboplatin plus pemetrexed or gefitinib alone. Progression-free survival (PFS), PFS2, and overall survival (OS) were sequentially analyzed as primary end points according to a hierarchical sequential testing method. Secondary end points were objective response rate (ORR), safety, and quality of life. RESULTS: The combination group demonstrated a better ORR and PFS than the gefitinib group (ORR, 84% v 67% [P < .001]; PFS, 20.9 v 11.9 months; hazard ratio for death or disease progression, 0.490 [P < .001]), although PFS2 was not significantly different (20.9 v 18.0 months; P = .092). Median OS in the combination group was also significantly longer than in the gefitinib group (50.9 v 38.8 months; hazard ratio for death, 0.722; P = .021). The rate of grade ≥ 3 treatment-related adverse events, such as hematologic toxicities, in the combination group was higher than in the gefitinib group (65.3% v 31.0%); there were no differences in quality of life. One treatment-related death was observed in the combination group. CONCLUSION: Compared with gefitinib alone, gefitinib combined with carboplatin plus pemetrexed improved PFS in patients with untreated advanced NSCLC with EGFR mutations with an acceptable toxicity profile, although its OS benefit requires further validation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Gefitinibe/administração & dosagem , Gefitinibe/efeitos adversos , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Qualidade de Vida , Taxa de Sobrevida
15.
Clin Cancer Res ; 26(4): 892-901, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31694833

RESUMO

PURPOSE: The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) is still under debate. Previous studies showed that LCNEC with different genomic characteristics might respond differently to different chemotherapy regimens. In this study, we sought to investigate genomic subtyping using cell-free DNA (cfDNA) analysis in advanced LCNEC and assess its potential prognostic and predictive value. EXPERIMENTAL DESIGN: Tumor DNA and cfDNA from 63 patients with LCNEC were analyzed by target-captured sequencing. Survival and response analyses were applied to 54 patients with advanced stage incurable disease who received first-line chemotherapy. RESULTS: The mutation landscape of frequently mutated cancer genes in LCNEC from cfDNA closely resembled that from tumor DNA, which led to a 90% concordance in genomic subtyping. The 63 patients with LCNEC were classified into small-cell lung cancer (SCLC)-like and non-small cell lung cancer (NSCLC)-like LCNEC based on corresponding genomic features derived from tumor DNA and/or cfDNA. Overall, patients with SCLC-like LCNEC had a shorter overall survival than those with NSCLC-like LCNEC despite higher response rate (RR) to chemotherapy. Furthermore, treatment with etoposide-platinum was associated with superior response and survival in SCLC-like LCNEC compared with pemetrexed-platinum and gemcitabine/taxane-platinum doublets, while treatment with gemcitabine/taxane-platinum led to a shorter survival compared with etoposide-platinum or pemetrexed-platinum in patients with NSCLC-like LCNEC. CONCLUSIONS: Genomic subtyping has potential in prognostication and therapeutic decision-making for patients with LCNEC and cfDNA analysis may be a reliable alternative for genomic profiling of LCNEC.


Assuntos
Carcinoma de Células Grandes/genética , Carcinoma Neuroendócrino/genética , Ácidos Nucleicos Livres/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Ácidos Nucleicos Livres/sangue , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Etoposídeo/administração & dosagem , Feminino , Genômica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Compostos Organoplatínicos/administração & dosagem , Pemetrexede/administração & dosagem , Prognóstico , Taxa de Sobrevida , Taxoides/administração & dosagem
16.
J Clin Pharm Ther ; 45(1): 179-184, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31545524

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Oxidative stress and inflammation are known to be high in non-small cell lung cancer (NSCLC). However, association of change in their levels with treatment response remains unaddressed. The present study evaluated change in blood levels of oxidative stress and inflammatory markers in NSCLC patients, after first course of platinum-based chemotherapy. METHODS: This prospective cohort study enrolled newly diagnosed NSCLC patients receiving either pemetrexed-carboplatin (group A) or paclitaxel-carboplatin (group B). Blood levels of malondialdehyde (MDA), reduced glutathione (GSH), interleukin-6 (IL-6), C-reactive protein (CRP) and interleukin-10 (IL-10) were measured at baseline and after first cycle. Response to treatment was noted after 2nd or 4th cycle, as available. Subgroup analysis was done (group B), based on paclitaxel dose/formulation. RESULTS: Of the 85 patients screened, 38 were enrolled with a mean age of 56.7 ± 9.2 years. Baseline levels of oxidative and inflammatory markers were not different between the groups and did not change significantly within the groups. Significant reduction in IL-6 was seen with three-weekly paclitaxel-carboplatin (from median 81.3 [range 8.6, 1006] pg/mL to 51.8 [11.4, 99.5] pg/mL; P = .025). C-reactive protein levels reduced with weekly nab-paclitaxel (P = .043). Change in levels did not relate with therapeutic response except for IL-6 which decreased in patients with partial response (from 102.6 [8.1, 1006] pg/mL to 38.9 [8.4, 99.5] pg/mL; P = .036). WHAT IS NEW AND CONCLUSION: Although the levels of oxidative and inflammatory markers varied following chemotherapy, trend indicates that IL-6 may be a potential marker of treatment response in NSCLC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Idoso , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Interleucina-6/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Pemetrexede/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
17.
J Clin Oncol ; 38(2): 124-136, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31411950

RESUMO

PURPOSE: Standard first-line therapy for EGFR-mutant advanced non-small-cell lung cancer (NSCLC) is an epidermal growth factor receptor (EGFR)-directed oral tyrosine kinase inhibitor. Adding pemetrexed and carboplatin chemotherapy to an oral tyrosine kinase inhibitor may improve outcomes. PATIENTS AND METHODS: This was a phase III randomized trial in patients with advanced NSCLC harboring an EGFR-sensitizing mutation and a performance status of 0 to 2 who were planned to receive first-line palliative therapy. Random assignment was 1:1 to gefitinib 250 mg orally per day (Gef) or gefitinib 250 mg orally per day plus pemetrexed 500 mg/m2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed (gefitinib plus chemotherapy [Gef+C]). The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS), response rate, and toxicity. RESULTS: Between 2016 and 2018, 350 patients were randomly assigned to Gef (n = 176) and Gef+C (n = 174). Twenty-one percent of patients had a performance status of 2, and 18% of patients had brain metastases. Median follow-up time was 17 months (range, 7 to 30 months). Radiologic response rates were 75% and 63% in the Gef+C and Gef arms, respectively (P = .01). Estimated median PFS was significantly longer with Gef+C than Gef (16 months [95% CI, 13.5 to 18.5 months] v 8 months [95% CI, 7.0 to 9.0 months], respectively; hazard ratio for disease progression or death, 0.51 [95% CI, 0.39 to 0.66]; P < .001). Estimated median OS was significantly longer with Gef+C than Gef (not reached v 17 months [95% CI, 13.5 to 20.5 months]; hazard ratio for death, 0.45 [95% CI, 0.31 to 0.65]; P < .001). Clinically relevant grade 3 or greater toxicities occurred in 51% and 25% of patients in the Gef+C and Gef arms, respectively (P < .001). CONCLUSION: Adding pemetrexed and carboplatin chemotherapy to gefitinib significantly prolonged PFS and OS but increased toxicity in patients with NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Gefitinibe/administração & dosagem , Gefitinibe/efeitos adversos , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Qualidade de Vida
18.
J Exp Ther Oncol ; 13(2): 131-138, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31881129

RESUMO

Background: Continuation maintenance therapy with pemetrexed (PEM) and bevacizumab (BEV) following induction therapy with cisplatin (CDDP), PEM, and BEV is beneficial in advanced non-squamous non-small-cell lung cancer (NS-NSCLC), but the survival benefit of addition of BEV to CDDP/PEM as induction therapy is still unclear. The aim of this phase II study was to evaluate the feasibility and safety of a CDDP/PEM/BEV regimen in Japanese patients with EGFR wild-type NS-NSCLC. Patients and Methods: This study included 25 patients who receive intravenous CDDP, PEM, and BEV (15 mg/kg) from August 2010 to February 2013. The primary endpoint of this study was the response rate (RR) and the secondary endpoint was progression free survival (PFS), overall survival (OS), and safety. Results: The median cycles of induction chemotherapy were four (range 1-6). RR was 64%. Most patients (64%) transitioned to maintenance therapy. The median PFS was 9.7 months. Median OS was 21.6 months. Haematological adverse events reaching grade 3 to 4 were neutropenia (8%) without febrile neutropenia, thrombocytopenia (4%), and anemia (4%). BEV-related non-haematological toxicities of grade 3/4 were hypertension (16%), thrombosis (4%), and gastrointestinal perforation (4%). Each adverse events was controllable, and there were no treatment-related deaths. Conclusions: CDDP/PEM/BEV regimen is effective and tolerable in patients with EGFR wild-type advanced NS-NSCLC, but should be paid attention to some BEV-related toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Cisplatino/administração & dosagem , Receptores ErbB , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Resultado do Tratamento
19.
Rev. Hosp. Ital. B. Aires (2004) ; 39(4): 146-148, dic. 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1099838

RESUMO

Los anticuerpos monoclonales que inhiben los puntos de control PD-1 y CTLA-4 se usan actualmente en el tratamiento del melanoma y cáncer metastásico de pulmón de células no pequeñas, entre otros. Se refiere el caso de una paciente con cáncer de pulmón en tratamiento con pembrolizumab. La paciente se presentó con edema facial y parálisis facial periférica. En el laboratorio se observó la hormona tirotrofina (TSH) elevada y se llegó al diagnóstico de hipotiroidismo por pembrolizumab. Inició tratamiento con levotiroxina con mejoría clínica. Se presenta este caso por el importante papel del dermatólogo en el manejo multidisciplinario del paciente oncológico. (AU)


Monoclonal antibodies that inhibit PD-1 and CTLA-4 control points are currently used in the treatment of melanoma and metastatic non-small cell lung cancer, among others. The case of a patient, with lung cancer being treated with Pembrolizumab. The patient was presented with facial edema and peripheral facial paralysis and in the laboratory the elevated hormone Tyrotrophin (TSH) was observed, the diagnosis of pembrolizumab hypothyroidism was reached. She started treatment with levothyroxine with clinical improvement. This case is presented by the important role of the dermatologist in the multidisciplinary management of the cancer patient. (AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Imunoterapia/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Tiroxina/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Tireotropina/análise , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas Supressoras de Tumor/efeitos dos fármacos , Dermatologia , Traumatismos Faciais , Paralisia Facial , Antígeno CTLA-4/efeitos dos fármacos , Antígeno CTLA-4/fisiologia , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Receptor de Morte Celular Programada 1/fisiologia , Pemetrexede/administração & dosagem , Melanoma/complicações , Melanoma/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Metástase Neoplásica/tratamento farmacológico
20.
Anticancer Res ; 39(11): 6241-6247, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704853

RESUMO

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Pulmonares/enzimologia , Mesotelioma/enzimologia , Proteína Quinase 1 Ativada por Mitógeno/análise , Neoplasias Pleurais/enzimologia , Serina-Treonina Quinases TOR/análise , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/mortalidade , Mesotelioma/terapia , Pessoa de Meia-Idade , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Terapia de Alvo Molecular , Pemetrexede/administração & dosagem , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/terapia , Pneumonectomia , Prognóstico , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo
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