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2.
N Engl J Med ; 383(14): 1328-1339, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997907

RESUMO

BACKGROUND: The efficacy and safety of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those of platinum-based chemotherapy, as first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC) with PD-L1 expression are not known. METHODS: We conducted a randomized, open-label, phase 3 trial involving patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay. Patients were assigned in a 1:1 ratio to receive atezolizumab or chemotherapy. Overall survival (primary end point) was tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat population whose tumors were wild-type with respect to EGFR mutations or ALK translocations. Within the population with EGFR and ALK wild-type tumors, overall survival and progression-free survival were also prospectively assessed in subgroups defined according to findings on two PD-L1 assays as well as by blood-based tumor mutational burden. RESULTS: Overall, 572 patients were enrolled. In the subgroup of patients with EGFR and ALK wild-type tumors who had the highest expression of PD-L1 (205 patients), the median overall survival was longer by 7.1 months in the atezolizumab group than in the chemotherapy group (20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P = 0.01). Among all the patients who could be evaluated for safety, adverse events occurred in 90.2% of the patients in the atezolizumab group and in 94.7% of those in the chemotherapy group; grade 3 or 4 adverse events occurred in 30.1% and 52.5% of the patients in the respective groups. Overall and progression-free survival favored atezolizumab in the subgroups with a high blood-based tumor mutational burden. CONCLUSIONS: Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type. (Funded by F. Hoffmann-La Roche/Genentech; IMpower110 ClinicalTrials.gov number, NCT02409342.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Análise de Sobrevida
3.
Medicine (Baltimore) ; 99(38): e22150, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957337

RESUMO

BACKGROUND: Nausea and vomiting are the most common complications after chemotherapy, which cannot be completely controlled even with commonly prescribed antiemetic drugs, particularly in patients receiving highly emetogenic chemotherapy Acupuncture therapy is an effective replacement method for chemotherapy-induced nausea and vomiting (CINV), which effectiveness and safety have been observed by many clinicians. However, different acupuncture treatments have various effectiveness. Based on enough clinical researches, the study aims to uses Bayesian network meta-analysis (NMA) to evaluate the effectiveness of different acupuncture therapies used for preventing CINV. METHODS: Authors will search PubMed/Medline, Cochrane library, Web of Science, Ebsco, Ovid/Embase, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine from setup time to July 2020. All randomized control trails meet the standard will be included. Quality evaluation of included studies will be implemented with Cochrane risk-of-bias tool. STATA 14.0 will be used to perform pairwise meta-analysis. Addis 1.16.8 (University Medical Center Groningen (UMCG), Groningen, NL) and OpenBUGS 3.2.3 (Medical Research Council (MRC), London, UK) will be used to conduct NMA. RESULTS: The results of this review will generate a comprehensive review of current evidence and be published on a peer-reviewed journal. CONCLUSION: The result of this systematic review and Bayesian NMA may offer better options for patients in relieving CINV.Systematic review registration number: INPLASY202070070.


Assuntos
Terapia por Acupuntura/métodos , Antineoplásicos/efeitos adversos , Náusea/prevenção & controle , Projetos de Pesquisa , Vômito/prevenção & controle , Teorema de Bayes , Humanos , Náusea/induzido quimicamente , Metanálise em Rede , Revisões Sistemáticas como Assunto , Vômito/induzido quimicamente
4.
Medicine (Baltimore) ; 99(33): e21695, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872042

RESUMO

BACKGROUND AND OBJECTIVES: Chemotherapy does not only affect cancer cells; it also affects, to a greater or lesser degree, all other cells in the body. This toxicity should be assessed according to its severity, frequency, and duration, taking into account objective and subjective dimensions in its assessment. This assessment is a highly relevant aspect when providing care to chemotherapy patients, mainly due to the impact of the treatment on the patient's quality of life, as well as the vital risk it may imply under certain circumstances. For all this, the objective of this study was to assess the relationship between chemotherapy-associated adverse reactions and health-related quality of life in breast cancer patients. MATERIALS AND METHODS: With this purpose, a descriptive cross-sectional study was developed on 110 breast cancer patients who were treated with docetaxel, epirubicin, and cyclophosphamide. RESULTS: It is worth highlighting the negative effect of nausea, dysgeusia, peripheral neuropathy, loss of appetite, myalgia, and peripheral edema on the quality of life. Likewise, it is worth mentioning peripheral neuropathy as the toxicity that affects a greater number of quality-of-life indicators. CONCLUSIONS: To sum up, it would be necessary to make health professionals aware of the importance of chemotherapy-associated adverse reactions.


Assuntos
Atividades Cotidianas/psicologia , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Neoplasias da Mama/psicologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
5.
Medicine (Baltimore) ; 99(33): e21559, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872006

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and provide updated information for clinical practice. METHODS: Pubmed, Embase, the Cochrane Library, and 3 Chinese literature databases were systematically searched. Randomized controlled trials comparing standard regimen (5-hydroxytryptamine-3 receptor antagonist and glucocorticoid) with aprepitant triple regimen (aprepitant plus the standard regimen) for preventing CINV were screened. Literature selection, data extraction, and quality evaluation were performed by 2 reviewers independently. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the meta-analysis using RevMan 5.3 software. RESULTS: A total of 51 randomized controlled trials were finally included in the systematic review. Compared with the standard regimen, the aprepitant triple regimen significantly improved the complete response in the overall (OR 1.88, 95% CI 1.71-2.07), acute (OR 1.96, 95% CI 1.65-2.32) and delayed (OR 1.96, 95% CI 1.70-2.27) phases, regardless of emetogenic risk of chemotherapy. Aprepitant could also significantly enhance the proportions of patients who have no emesis, nausea, or use of rescue medication respectively in the overall, acute and/or delayed phases. Aprepitant was found to be associated with decreased risk of constipation (OR 0.85, 95% CI 0.74-0.97), but increased the incidence of hiccup (OR 1.26, 95% CI 1.05, 1.51). There were no statistically significant differences between the 2 groups on other safety outcomes. CONCLUSION: The aprepitant triple regimen is effective for the prevention of CINV in patients being treated with moderately or highly emetogenic chemotherapy, and has a significant tendency to reduce the risk of constipation and increase the incidence of hiccup.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Aprepitanto/uso terapêutico , Náusea/prevenção & controle , Vômito/prevenção & controle , Humanos , Náusea/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Vômito/induzido quimicamente
6.
J UOEH ; 42(3): 261-266, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879190

RESUMO

Radiation recall pneumonitis is a phenomenon in which a recall-triggering drug induces an acute inflammatory reaction in the lungs, corresponding to a previously irradiated area. Radiation recall reactions have been reported to occur following treatments with various cytotoxic anticancer agents and molecular-targeting drugs; however, only a few reports have described immune checkpoint inhibitor-induced radiation recall pneumonitis. We report a case of radiation recall pneumonitis induced by pembrolizumab in a patient with the postoperative local recurrence of non-small cell lung cancer. This case demonstrated that pembrolizumab might cause severe radiation recall pneumonitis, even after typical radiation pneumonitis has been resolved.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Doenças Assintomáticas , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Pneumonite por Radiação/etiologia , Radioterapia/efeitos adversos , Terapia Combinada , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia
7.
Isr Med Assoc J ; 9(22): 498-502, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32954696

RESUMO

BACKGROUND: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment. OBJECTIVES: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD. RESULTS: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e' septal (P < 0.001). CONCLUSIONS: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/epidemiologia , Disfunção Ventricular Esquerda/epidemiologia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Cardiotoxicidade/etiologia , Feminino , Humanos , Israel , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente
8.
Anticancer Res ; 40(9): 5255-5261, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878814

RESUMO

BACKGROUND/AIM: Treatment of recurrent platinum-resistant ovarian cancer remains challenging due to the development of resistance to chemotherapy. Cabazitaxel is a new taxane that has demonstrated beneficial effect in prostate cancer patients resistant to docetaxel. Therefore, it could be anticipated to possibly also have an effect on chemotherapy resistant ovarian cancer. PATIENTS AND METHODS: Twenty-six patients with chemotherapy-resistant epithelial ovarian cancer, fallopian tube or peritoneal cancer were treated with cabazitaxel at a dose of 25 mg/m2 (on day 1 of each 3-week cycle), until progression or inacceptable toxicity, between September 2015 and April 2018. The fraction of patients without progression after three months of treatment was the primary endpoint. Prophylaxis with granulocyte colony-stimulating factor (G-CSF) was prescribed to all patients. RESULTS: The median number of cabazitaxel infusions was 4 (range=1-18). In general, cabazitaxel was well-tolerated. The fraction of patients alive and without progression after 3 months of treatment was 54% (14/26). The response rate was 46% (12/26) according to the Gynecological Cancer Intergroup (GCIG) criteria for CA125. Partial response (PR), evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST), was found in 4/26 patients (15%). By intention-to-treat analysis, the median progression-free survival (PFS) was 3.9 months (95% CI=1.9-4.4) using the combination of CA125 or RECIST (whichever came first), while the median overall survival (OS) was 8.4 months (95% CI=5.1-11.0). CONCLUSION: Cabazitaxel holds promise as a drug in recurrent platinum-resistant ovarian cancer. It demonstrated efficacy and in general, the toxicity was manageable.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Taxoides/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Prognóstico , Qualidade de Vida , Recidiva , Retratamento , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
9.
Anticancer Res ; 40(9): 5271-5276, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878816

RESUMO

BACKGROUND/AIM: Hepatic encephalopathy is an adverse event resulting from lenvatinib use in patients with hepatocellular carcinoma (HCC). We analyzed the influence of lenvatinib on portal venous flow velocity (PVV) and serum ammonia concentration. PATIENTS AND METHODS: Eleven patients with unresectable HCC were enrolled, including three with modified albumin-bilirubin (mALBI) grade 1, three with grade 2a, and five with grade 2b. PVV was measured by Doppler ultrasound sonography before and on day 2 of administration. RESULTS: Out of 11 patients, one developed hepatic encephalopathy. PVV was reduced in 10 patients, and the change from baseline was significantly correlated with lenvatinib dosage. The increase in serum ammonia concentration was affected by lenvatinib dose and baseline hepatic function as a threshold between mALBI grade 2a and 2b statistically. There was no correlation between changes in PVV and serum ammonia concentration. CONCLUSION: Lenvatinib might directly disturb hepatocyte metabolism to result in increased serum ammonia concentration.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Hiperamonemia/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Bilirrubina/sangue , Carcinoma Hepatocelular/diagnóstico , Suscetibilidade a Doenças , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Hiperamonemia/diagnóstico , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Veia Porta/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Fatores de Risco
10.
Anticancer Res ; 40(9): 5291-5294, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878819

RESUMO

BACKGROUND/AIM: Palbociclib is an FDA-approved cyclin-dependent kinase inhibitor for the treatment of advanced breast cancer. Limited information is available regarding the toxicity of palbociclib and concurrent radiation therapy. CASE REPORT: Herein, we report a case of esophageal toxicity in a patient treated with palbociclib and radiation therapy. A 63-year-old woman was treated with palbociclib followed by palliative radiation therapy. The patient presented three days after completing radiation therapy with severe odynophagia, and dysphagia and was found to have grade 2-3 esophageal ulcers. Palbociclib and radiation therapy was held on admission, and a resolution of her symptoms and improvement in her oral intake was noted at which time she was restarted on palbociclib with no further radiation treatment. CONCLUSION: Caution is advised when patients are undergoing concurrent palbociclib and even low-dose palliative radiation treatment. In these patients, providers should maintain a high index of suspicion for toxicities such as dermatitis or mucositis.


Assuntos
Antineoplásicos/efeitos adversos , Mucosite/diagnóstico , Mucosite/etiologia , Piperazinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Endoscopia Gastrointestinal , Feminino , Humanos , Cuidados Paliativos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Dosagem Radioterapêutica , Radioterapia Adjuvante/métodos , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
11.
Anticancer Res ; 40(9): 5313-5317, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878823

RESUMO

BACKGROUND/AIM: Imatinib (IM) is the standard-of-care treatment for most chronic myeloid leukemia (CML) patients in chronic phase (CP). However, some patients suffer from low-grade side-effects that, in the long run, severely affect the quality of life and require treatment discontinuation due to toxicities. Fortunately, there are several therapeutic alternatives for these patients. Among them, the second-generation tyrosine kinase inhibitor dasatinib (DAS), used as second-line treatment, has shown to be a valid option in patients with CP-CML after intolerance to prior IM. PATIENTS AND METHODS: Herein, we report on seven CP-CML patients who achieved a stable major molecular response (MMR) with IM-therapy, but were shifted to DAS treatment due to recurrent low-grade IM-intolerances (grades 1-2). RESULTS AND CONCLUSION: All patients received conventional DAS treatment with a median daily dose of 83.3 mg. Treatment was well tolerated and side-effects were mild. In addition, after a median follow-up of 25 months (range=24-43 months) a deep molecular response (DMR) (either MR4 or MR4.5) was achieved in all patients after 24 months of treatment. This finding, although limited to a small cohort of CP-CML patients, supports the view that a therapy switch from IM to DAS induces a reduction of symptom burden, improves patient compliance and shows clinical efficacy in achieving and sustaining deep molecular responses.


Assuntos
Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cooperação do Paciente , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Retratamento , Resultado do Tratamento
12.
Medicine (Baltimore) ; 99(35): e22042, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871961

RESUMO

BACKGROUND: Many cancer patients experience gastrointestinal adverse reaction during chemotherapy. Pharmacological interventions are commonly used to treat chemotherapy-induced gastrointestinal side effects but have various limitations. Clinical trials have indicated that moxibustion may alleviate gastrointestinal dysfunction and improve quality of life (QoL) after chemotherapy. This study aims to assess the efficacy and safety of moxibustion for chemotherapy-induced gastrointestinal adverse reaction through a systematic review and meta-analysis. METHODS: All randomized controlled trials (RCTs) related to moxibution targeting chemotherapy-induced gastrointestinal adverse reaction will be searched in online databases, such as PubMed, EMBASE, the Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP Database) and WanFang Database from their inception to May 1, 2020. The primary outcome is the incidence and severity of chemotherapy-related gastrointestinal toxicities (nausea and vomiting, diarrhea and constipation). The secondary outcomes include the quality of life, biological parameters' alteration, and adverse events. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 researchers. The Cochrane Collaboration's Review Manager (RevMan 5.3) software will be used to conduct the direct meta-analysis. RESULTS: This study will provide a comprehensive review of the available evidence for the treatment of chemotherapy-induced gastrointestinal adverse reaction with moxibustion. CONCLUSION: The conclusion of this study will provide evidence to judge whether moxibustion is an effective and safety therapeutic intervention for chemotherapy-induced gastrointestinal adverse reaction. PROSPERO REGISTRATION NUMBER: CRD42020182990.


Assuntos
Gastroenteropatias/terapia , Moxibustão , Antineoplásicos/efeitos adversos , Gastroenteropatias/induzido quimicamente , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
13.
N Engl J Med ; 383(10): 944-957, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32877583

RESUMO

BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), MET exon 14 skipping mutations occur in 3 to 4% and MET amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation. METHODS: We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with MET-dysregulated advanced NSCLC. Patients were assigned to cohorts on the basis of previous lines of therapy and MET status (MET exon 14 skipping mutation or MET amplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments. RESULTS: A total of 364 patients were assigned to the cohorts. Among patients with NSCLC with a MET exon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients who had received one or two lines of therapy previously and in 68% (95% CI, 48 to 84) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively. Limited efficacy was observed in previously treated patients with MET amplification who had a gene copy number of less than 10 (overall response in 7 to 12% of patients). Among patients with MET amplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2. CONCLUSIONS: Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation, particularly in those not treated previously. The efficacy in MET-amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects. (Funded by Novartis Pharmaceuticals; GEOMETRY mono-1 ClinicalTrials.gov number, NCT02414139.).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Triazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Edema/induzido quimicamente , Éxons , Feminino , Dosagem de Genes , Humanos , Imidazóis/efeitos adversos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-met/genética , Triazinas/efeitos adversos
14.
Lancet Haematol ; 7(10): e724-e736, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32896301

RESUMO

BACKGROUND: Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukaemia (AML) who are 75 years or older, or unfit for intensive chemotherapy. Pharmacodynamic studies have suggested superiority of the longer 10-day regimen of decitabine that has shown promising results in patients with high-risk AML in phase 2 trials. We hypothesised that venetoclax with 10-day decitabine could have improved activity in patients with newly diagnosed AML and those with relapsed or refractory AML, particularly in high-risk subgroups. METHODS: This single centre, phase 2 trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). The study enrolled older patients (aged >60 years) with newly diagnosed AML, not eligible for intensive chemotherapy; secondary AML (progressed after myelodysplastic syndrome or chronic myelomonocytic leukaemia); and relapsed or refractory AML. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less, white blood cell count less than 10 × 109 per L, and adequate end-organ function. Patients with favourable-risk cytogenetics (eg, t[15;17] or core-binding factor AML) or who had received previous BCL2-inhibitor therapy were excluded. Patients received decitabine 20 mg/m2 intravenously for 10 days with oral venetoclax 400 mg daily for induction, followed by decitabine for 5 days with daily venetoclax for consolidation. The primary endpoint was overall response rate. The secondary endpoints analysed within this report include safety, overall survival, and duration of response, in keeping with recommendations of European LeukemiaNet 2017 guidelines. All patients who received at least one dose of treatment were eligible for safety and response assessments. The trial was registered on ClinicalTrials.gov (NCT03404193) and continues to accrue patients. FINDINGS: Between Jan 19, 2018, and Dec 16, 2019, we enrolled 168 patients; 70 (42%) had newly diagnosed AML, 15 (9%) had untreated secondary AML, 28 (17%) had treated secondary AML, and 55 (33%) had relapsed or refractory AML. The median age was 71 years (IQR 65-76) and 30% of patients had ECOG performance status of 2 or higher. The median follow-up for all patients was 16 months (95% CI 12-18; actual follow-up 6·5 months; IQR 3·4-12·4). The overall response rate was 74% (125 of 168 patients; 95% CI 67-80) and in disease subgroups were: 89% in newly diagnosed AML (62 of 70 patients; 79-94), 80% in untreated secondary AML (12 of 15 patients; 55-93), 61% in treated secondary AML (17 of 28 patients; 42-76), and 62% in relapsed or refractory AML (34 of 55 patients; 49-74). The most common treatment-emergent adverse events included infections with grades 3 or 4 neutropenia (n=79, 47%) and febrile neutropenia (n=49, 29%). 139 (83%) of 168 patients had serious adverse events, most frequently neutropenic fever (n=63, 38%), followed by pneumonia (n=17, 10%) and sepsis (n=16, 10%). The 30-day mortality for all patients was 3·6% (n=6, 95% CI 1·7-7·8). The median overall survival was 18·1 months (95% CI 10·0-not reached) in newly diagnosed AML, 7·8 months (2·9-10·7) in untreated secondary AML, 6·0 months (3·4-13·7) in treated secondary AML, and 7·8 months (5·4-13·3) relapsed or refractory AML. The median duration of response was not reached (95% CI 9·0-not reached) in newly diagnosed AML, 5·1 months (95% CI 0·9-not reached) in untreated secondary AML, not reached (95% CI 2·5-not reached) in previously treated secondary AML, and 16·8 months (95% CI 6·6-not reached) in relapsed or refractory AML. INTERPRETATION: Venetoclax with 10-day decitabine has a manageable safety profile and showed high activity in newly diagnosed AML and molecularly defined subsets of relapsed or refractory AML. Future larger and randomised studies are needed to clarify activity in high-risk subsets. FUNDING: US National Institutes of Health and National Cancer Institute.


Assuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Decitabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Decitabina/administração & dosagem , Decitabina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento
15.
Eur J Cancer ; 137: 235-239, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32805640

RESUMO

The outbreak of the Coronavirus disease (COVID-19) pandemic has deeply challenged healthcare systems and care of patients with cancer. Phase 1 studies are among the most complicated clinical trials and require thorough patient selection, as well as intensive patient monitoring. In this perspective, we discuss the key factors that should be considered for the conduct of phase 1 trials and management of COVID-19-positive patients with cancer enrolled in such trials. We notably present the risks and challenges raised by COVID-19-infected phase 1 patients, in terms of safety, toxicity causality assessment, drug efficacy evaluation and clinical research priorities. We finally propose some guidelines for the conduct of phase 1 trials and management of COVID-19-infected patients in a pandemic time.


Assuntos
Antineoplásicos/efeitos adversos , Ensaios Clínicos Fase I como Assunto/normas , Infecções por Coronavirus/terapia , Neoplasias/tratamento farmacológico , Seleção de Pacientes , Pneumonia Viral/terapia , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Medicina Baseada em Evidências/normas , Humanos , Controle de Infecções/normas , Oncologia/normas , Neoplasias/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Guias de Prática Clínica como Assunto , Resultado do Tratamento
16.
JCO Glob Oncol ; 6: 1298-1305, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32795196

RESUMO

PURPOSE: As a result of their immunocompromised status associated with disease and treatment, patients with cancer face a profound threat for higher rates of complications and mortality if they contract the coronavirus disease 2019 infection. Medical oncology communities have developed treatment modifications to balance the risk of contracting the virus with the benefit of improving cancer-related outcomes. METHODS: We systemically examined our community cancer center database to display patterns of change and to unveil factors that have been considered with each decision. We studied a cohort of 282 patients receiving treatment and found that 159 patients (56.4%) had treatment modifications. RESULTS: The incidence of treatment modification was observed in patients undergoing adjuvant and neoadjuvant (41.4%), palliative (62.9%), or injectable endocrine or bone-modulating only (76.0%) treatments. Modifications were applied to regimens with myelosuppressive (56.5%), immunosuppressive (69.2%), and immunomodulating (61.5%) potentials. These modifications also affected intravenous (54.9%) and subcutaneous injectable treatments (62.5%) more than oral treatments (15.8%). Treatment modifications in 112 patients (70.4%) were recommended by providers, and 47 (29.6%) were initiated by patients. The most common strategy of modification was to skip or postpone a scheduled treatment (49%). Among treatment with no modifications, treatment regimens were maintained in patients who tolerated treatment well (37.0%), in treatments with curative intent (22%), and in symptomatic patients who required treatment (14%). CONCLUSION: Our observation and analysis suggested that the primary goal of treatment modification was to decrease potential exposure. The pattern also reflected the negative impact of the pandemic on health care providers who initiated these changes. Providers have to consider individualized recommendations incorporating multiple factors, such as tolerance, potential toxicity, treatment nature and route, and disease severity.


Assuntos
Antineoplásicos/administração & dosagem , Betacoronavirus , Infecções por Coronavirus , Neoplasias/terapia , Pandemias , Pneumonia Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Centros Comunitários de Saúde , Feminino , Humanos , Masculino , Oncologia/normas , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias/patologia , Cidade de Nova Iorque , Cuidados Paliativos/métodos , Aceitação pelo Paciente de Cuidados de Saúde
17.
Medicine (Baltimore) ; 99(34): e21770, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846805

RESUMO

BACKGROUND: As an alternative for constipation after cancer chemotherapy, Chinese medicine has gradually attracted the attention of clinicians based on the theory of syndrome differentiation and treatment. However, due to the lack of evidence-based medical evidence, the author designed the program to evaluate the effectiveness and safety of Chinese medicine. METHODS: From the beginning to August 2020, 8 electronic databases will be searched. Two of our researchers will independently conduct research selection, data extraction, and risk assessment of bias. We will use Review Manager 5.3 software for meta-analysis and heterogeneity assessment. In addition, we will use the grading of recommendations assessment, development, and evaluation to evaluate the evidence quality. RESULTS: This study will demonstrate an evidence-based review of traditional Chinese medicine (TCM) for constipation after cancer chemotherapy. CONCLUSION: The study will provide clear evidence to assess the effectiveness and side effects of TCM for constipation after cancer chemotherapy. TRIAL REGISTRATION NUMBER: INPLASY202070027.


Assuntos
Antineoplásicos/efeitos adversos , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
18.
Medicine (Baltimore) ; 99(34): e21826, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846826

RESUMO

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the primary treatment in treating with EGFR mutant nonsmall cell lung cancer (NSCLC). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of the third-generation EGFR-TKI, osimertinib, and summarize the risk factors associating with outcome after osimertinib treatment. METHOD: The Ovid Medline, Embase, Cochrane Library, and Pubmed were systematically searched due to December 10, 2019. All the studies that mentioned the overall survival (OS), progression-free survival (PFS), treatment response, and adverse events (AEs) of osimertinib were involved in our study. Hazard ratio (HR) with 95% confidence intervals was used for comparing OS and PFS. RESULT: A total of 47 studies were included in the systematic review, of which 14 studies were used to compare the efficacy between osimertinib and other EGFR-TKI or chemotherapy. Patients treating with osimertinib favors a higher OS and PFS in all the patients (HR = 0.56 and 0.38, P < .001, respectively), and in subgroup analysis, compared with other treatments. Median 55% T790 mutant NSCLC patients might experience partial response, and 25% of patients remained as stable disease. The incidence of severe AE ranged from 0% to 5%, and the most common severe AE was pneumonia (3%). Patients with the T858R mutation may have a better OS than Del 19 mutation (HR = 0.55, P = .037), while patients who have a smoking history may have a higher risk of progression than never-smoker patients (HR = 1.47, P = .028). CONCLUSION: Osimertinib has an impressive antitumor activity compared with prior EGFR-TKI and chemotherapy with an acceptable response and tolerable AEs. EGFR mutation type and smoking status were the risk factors for mortality and progression in NSCLC patients.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Acrilamidas/efeitos adversos , Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Fumar Cigarros , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Pneumonia/induzido quimicamente , Intervalo Livre de Progressão , Taxa de Sobrevida
19.
Medicine (Baltimore) ; 99(34): e21876, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846844

RESUMO

BACKGROUND: Cancer continues to be a severe global health problem and the leading cause of death worldwide. Chemotherapy as the main treatment has various side effects, of which marrow suppression is the most common one. Acupuncture had shown clinical effects for marrow suppression after chemotherapy in many studies. However, the efficacy and safety of acupuncture therapy for marrow suppression after chemotherapy remains unclear. OBJECTIVE: This protocol aims to evaluate the efficacy and safety of acupuncture for marrow suppression after chemotherapy according to the existing randomized controlled trials. METHODS AND ANALYSIS: The randomized controlled trials on acupuncture therapy for marrow suppression after chemotherapy will be searched in the database of Embase, PubMed and Cochrane Library, Allied and Complementary Medicine Database (AMED), Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Infrastructure (CNKI), WanFang Database (WF), and related registration platforms (WHO ICTRP, Clinical Trials, and Chinese Clinical Trial Register [ChiCTR]), Grey Literature Database from inception to 1 August 2020. The primary outcomes will be assessed using white blood cell (WBC) count, platelet count, hemoglobin count and the number of neutrophils (N). Review Manager V.5.3 software will be applied for statistical analyses. We will measure the risk of bias of the included studies with Cochrane Collaboration Risk of Bias Tool. Finally, Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) will be used to grade the overall quality of evidence. And we will use the intra-group correlation coefficient to assess the consistency of reviewers. RESULT: This systematic review and meta-analysis will put a high-quality synthesis of the efficacy and safety of acupuncture treatment in marrow suppression after chemotherapy. CONCLUSION: The conclusion of this systematic review will provide evidence to assess acupuncture therapy is an efficacy and safe intervention to treat and control marrow suppression after chemotherapy. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020163336.


Assuntos
Terapia por Acupuntura/métodos , Antineoplásicos/efeitos adversos , Células da Medula Óssea/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Tratamento Farmacológico/métodos , Feminino , Hemoglobinas/análise , Humanos , Contagem de Leucócitos/métodos , Masculino , Neoplasias/tratamento farmacológico , Neutrófilos/citologia , Contagem de Plaquetas/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
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