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1.
Anticancer Res ; 41(9): 4505-4513, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475076

RESUMO

BACKGROUND: The tumor vascular microenvironment has an important role in tumor progression and metastasis. The objective of this study was to assess the significance of metastatic hepatic tumor vascular microenvironment in relation to the response to systemic fluorouracil-based chemotherapy [folinic acid/fluorouracil/oxaliplatin (FOLFOX) or folinic acid/fluorouracil/irinotecan (FOLFIRI)]. PATIENTS AND METHODS: A total of 48 consecutive patients with colorectal cancer (CRC) with hepatic metastasis were retrospectively reviewed, and factors such as metastatic tumor vascular microenvironment, chemotherapy response and hepatic resection, were analyzed. Tumor angiogenesis was microscopically evaluated by microvessel density (MVD) in sections stained immunochemically with antibody to CD34 in patients with hepatic resection. Angiogenesis in the tumor microenvironment in association with ring enhancement (RE) on computed tomography (CT) was also examined. RESULTS: Microscopic examination revealed that peripheral RE on CT of the metastatic tumor was associated with tumor angiogenesis by MVD. The overall response rate after six courses of first-line chemotherapy for liver metastasis with RE on CT was 64% (23/36), whereas the response rate for those without RE was 25% (3/12), which was significantly lower, although the survival of patients with RE-positive and RE-negative tumors did not differ significantly. CONCLUSION: Peripheral RE of metastatic hepatic tumor on CT was associated with angiogenesis in the tumor microenvironment and higher chemotherapy response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/metabolismo , Angiografia por Tomografia Computadorizada , Feminino , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Leucovorina/farmacologia , Leucovorina/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/farmacologia , Compostos Organoplatínicos/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos
2.
Rinsho Ketsueki ; 62(8): 1077-1084, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497194

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma affecting about 14,000 patients per year in Japan. Recent progress in molecular genetic investigation has clarified the underlying mechanism of this heterogeneous disease applied to therapeutic developments. R-CHOP therapy was established as a standard regimen for DLBCL and provides a cure in many patients. However, about 30-40% of patients still develop relapsed/refractory (R/R) disease. The development of effective treatments for R/R DLBCL patients is thus an urgent issue. The development of immunotherapy for intractable DLBCL patients such as anti-CD19 chimeric antigen receptor (CAR)-T therapy and bispecific T-cell engager (BiTE) has recently progressed. This new modality demonstrates efficacy in patients with resistance to conventional anticancer drugs. The advent of emerging immunotherapy is a paradigm shift in lymphoma treatment and is important for clinicians to catch up with these changes.


Assuntos
Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Antígenos CD19 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Rituximab/uso terapêutico
3.
Rinsho Ketsueki ; 62(8): 1102-1111, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497197

RESUMO

Four cycles of ABVD followed by 30 Gy IFRT (ISRT) is a standard regimen, as an initial treatment, for patients with early-stage classical Hodgkin lymphoma (cHL), whereas 2 cycles of ABVD followed by 20 Gy IFRT (ISRT) is an alternative regimen for those with favorable early-stage cHL. For patients with unfavorable early-stage cHL including bulky disease, local radiotherapy can be safely omitted if negative findings on interim PET are obtained after 2 cycles of escalated BEACOPP plus 2 cycles of ABVD. ABVD (6/8 cycles) or brentuximab vedotin (BV) with concurrent AVD (6 cycles) is a standard regimen for patients with advanced-stage cHL. For elderly cHL patients (60 years of age or older) and multiple comorbidities, the risk of treatment-related adverse events is higher, which can potentially lead to poor outcomes. BV with sequential AVD therapy, which is a unique combination strategy, has been developed for elderly cHL patients. The combination of anti-PD-1 antibodies with AVD therapies is currently being evaluated in some clinical trials. This review includes current evidence that primarily focuses on randomized clinical trials for newly diagnosed adult cHL patients and management points in clinical practice for those patients.


Assuntos
Doença de Hodgkin , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Estadiamento de Neoplasias , Vimblastina/uso terapêutico
4.
Rinsho Ketsueki ; 62(8): 1112-1120, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497198

RESUMO

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive non-Hodgkin lymphomas (NHLs) with poor prognoses as compared with those of B-cell NHLs. CHOP or CHOP-like regimen has been considered to be the standard treatment for almost all pathological subtypes of PTCL; however, these regimens result in low complete response rate and short progression-free survival (PFS). Due to these insufficient results with CHOP-based chemotherapy, there is an urgent need for more effective and newer therapeutic strategies. The positive results of the ECHELON-2 study, which demonstrated significantly longer PFS with brentuximab vedotin plus CHP therapy in the frontline treatment for CD30-positive PTCLs, have a great impact on our clinical practice. At present, translational research is being actively conducted to elucidate molecular biology in PTCLs, and deep understanding of the underlying molecular mechanism of PTCLs would produce changes in disease classification. Until now, clinical development of novel agents based on the clinical classification has been carried out for all PTCL subtypes, but from now, treatment development based on molecular biology will be strongly required.


Assuntos
Linfoma de Células T Periférico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brentuximab Vedotin , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamento farmacológico
5.
Rinsho Ketsueki ; 62(8): 1149-1159, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497202

RESUMO

Multiple myeloma has been known as an incurable disease; however, since the approval of bortezomib in Japan in 2006 as the treatment for relapsed and refractory multiple myeloma, novel agents such as immunomodulatory drugs (IMIDs) and antibodies have been introduced one after another. Hence, progression-free survival and overall survival rates have markedly improved, regardless of the transplantation indication, and we have entered an era of a possible cure. Now that long-term survival can be expected, some clinical issues exist: 1) when to start treatment, 2) what regimen to choose for initial treatment, 3) how to continue treatment including maintenance therapy, 4) what to do for supportive care, and 5) what to choose for relapse treatment. The answers to these questions should be revised year-by-year according to the evidence from new clinical trials. This paper will discuss the current state of knowledge based on the latest evidence on treatment strategies for patients with myeloma who are ineligible for transplantation.


Assuntos
Mieloma Múltiplo , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Humanos , Japão , Mieloma Múltiplo/tratamento farmacológico
6.
World J Surg Oncol ; 19(1): 272, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507562

RESUMO

BACKGROUND: To evaluate whether the addition of taxanes to platinum and fluoropyrimidines in adjuvant chemotherapy would result in longer survival than platinum plus fluoropyrimidines in gastric cancer patients who received D2 gastrectomy. METHODS: Data of patients with gastric adenocarcinoma who received D2 gastrectomy and adjuvant chemotherapy with platinum plus fluoropyrimidines or taxanes, platinum plus fluoropyrimidines was retrospectively collected and analyzed. 1:1 Propensity score matching analysis was used to balance baseline characteristics between two groups. Survival curves were estimated using Kaplan-Meier method, and the differences were compared using the log-rank test. RESULTS: Four hundred twenty-five patients in the platinum plus fluoropyrimidines group and 177 patients in the taxanes, platinum plus fluoropyrimidines group were included into analysis. No statistical differences in disease-free survival and overall survival were observed between two groups. After propensity score matching, 172 couples of patients were matched, the baseline characteristics were balanced. The median disease-free survival were 15.8 months (95% CI, 9.3~22.4) in the platinum plus fluoropyrimidines group and 22.6 months (95% CI, 15.9~29.4) in the taxanes, platinum plus fluoropyrimidines group (HR = 0.63; 95% CI, 0.48~0.85; P = 0.002). The median overall survival was 25.4 months for patients in the platinum plus fluoropyrimidines group (95% CI, 19.4~31.3) and 33.8 months (95% CI, 23.5~44.2) for those in the taxanes, platinum plus fluoropyrimidines group (HR = 0.68; 95% CI, 0.53-0.87; log-rank test, P = 0.002). CONCLUSIONS: For gastric adenocarcinoma patients, the adjuvant triplet combination of taxanes, platinum, and fluoropyrimidines regimen after D2 gastrectomy was superior to platinum plus fluoropyrimidines regimen in disease-free survival as well as overall survival. TRIAL REGISTRATION: This project has been registered in the Chinese Clinical Trial Registry ( ChiCTR1800019978 ).


Assuntos
Platina , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Gastrectomia , Humanos , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxoides/uso terapêutico
7.
Gan To Kagaku Ryoho ; 48(9): 1165-1167, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34521797

RESUMO

A 74-year-old man presented to our hospital because of anorexia. Upper gastrointestinal endoscopy revealed type 3 gastric cancer. Further examination disclosed metastasis to the perigastric lymph nodes and to the liver, and a diagnosis of non- resectable advanced gastric cancer(cT4N2H1P0M0)in cStage Ⅳ was made. A total of 4 courses of S-1 plus oxaliplatin therapy(80 mg/body/day and 100 mg/m2/cycle, respectively, for 2 weeks followed by a 1-week rest)were administered as the primary chemotherapy. Then, another metastasis to the abdominal lymph nodes and increased liver metastasis were found; thus, the patient's condition was rated as progressive disease(PD). Secondary chemotherapy comprising 10 courses of weekly nab-paclitaxel(nab-PTX)plus ramucirumab(RAM)therapy(100 mg/m2 on days 1, 8, and 15 and 8 mg/kg on days 1 and 15, respectively, every 4 weeks)were administered. Although temporary reductions in the perigastric lymph node metastasis and liver metastasis as compared with the baseline were observed, another metastasis to the abdominal lymph nodes occurred subsequently, resulting in PD. As tertiary chemotherapy, nivolumab therapy(240 mg/body, every 3 weeks) was repeated up to a total of 30 courses over 13 months. This therapy was markedly effective, achieving a near complete response. The patient is currently being followed up as an outpatient.


Assuntos
Nivolumabe , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Linfonodos , Metástase Linfática , Masculino , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico
8.
Gan To Kagaku Ryoho ; 48(9): 1169-1171, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34521798

RESUMO

Ramucirumab monotherapy is one of the conditionally recommended regimens in second-line chemotherapy for advanced gastric cancer. However, there are few clinical data on ramucirumab monotherapy in Japanese patients. Herein, we present 4 case reports of advanced gastric cancer patients who received ramucirumab monotherapy. The 4 patients' age ranged from 65-81 years old(median: 70 years old), with a 3:1 male to female ratio. Since all cases were in poor performance status, administration of cell-killing anticancer drugs such as paclitaxel was contraindicated, and ramucirumab monotherapy was selected as an alternative. Ramucirumab was administrated 2-8 times(median: 3 times), resulting to a stable disease in 1 patient, and progression-free survival was noted to be 3-16 weeks(median: 5 weeks). Regarding complications, Grade 2 hypertension occurred in 1 patient, and no serious adverse events were observed. Ramucirumab monotherapy is a well-tolerated second-line chemotherapy for patients with advanced gastric cancer in poor performance status, and it is expected to have some disease control effect.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico
9.
Gan To Kagaku Ryoho ; 48(9): 1173-1175, 2021 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-34521799

RESUMO

A 70-year-old man, who had undergone distal gastrectomy for early gastric cancer at 63-year-old, had multiple liver metastases from remnant gastric cancer, which was diagnosed as cT3(SS), N0, M1, cStage Ⅳ. After a regimen consisting of 8 courses of capecitabine plus oxaliplatin and 2 courses of S-1 was administered, clinical CR was confirmed for the remnant gastric cancer and multiple liver metastases. Chemotherapy was administered for 10 months and discontinued for side effects and the needs of the patient. Anticoagulant drugs were administered for the onset of cerebral infarction after he vomited blood. A gastric ulcer in the oral side of the anastomotic portion was detected and diagnosed as poorly differentiated adenocarcinoma. Multiple liver metastases could not be detected by PET-CT, and we performed a total gastrectomy of the remnant stomach. The patient remains relapse-free 4 years and 10 months after chemotherapy(3 years and 10 months after discontinuing chemotherapy).


Assuntos
Neoplasias Hepáticas , Neoplasias Gástricas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Gastrectomia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Oxaliplatina/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
10.
Eur Rev Med Pharmacol Sci ; 25(16): 5310-5317, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34486707

RESUMO

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV. PATIENTS AND METHODS: This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA). RESULTS: During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox. CONCLUSIONS: This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.


Assuntos
Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Palonossetrom/uso terapêutico , Piridinas/uso terapêutico , Idoso , Antieméticos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , COVID-19 , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Náusea/prevenção & controle , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Palonossetrom/administração & dosagem , Pandemias , Estudos Prospectivos , Piridinas/administração & dosagem , Vômito/prevenção & controle
11.
BMJ Case Rep ; 14(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518180

RESUMO

Primary central nervous system lymphoma (PCNSL) is infrequent and often poses diagnostic conundrums due to its protean manifestations. We present the case of a South Asian young man presenting with raised intracranial pressure and a lymphocytic cerebrospinal fluid (CSF) with pronounced hypoglycorrhachia. Progression of the neuro-ophthalmic signs while on early stages of antitubercular treatment led to additional investigations that produced a final diagnosis of primary leptomeningeal lymphoma. Treatment with chemoimmunotherapy (methotrexate, cytarabine, thiotepa and rituximab (MATRix)) achieved full radiological remission followed by successful autologous transplant. This case highlights the difficulties and diagnostic dilemmas when PCNSL presents as a chronic meningeal infiltrative process. While contextually this CSF is most often indicative of central nervous system tuberculosis and justifies empirical treatment initiation alone, it is essential to include differential diagnoses in the investigation work-up, which also carry poor prognosis without timely treatment. High suspicion, multidisciplinary collaboration and appropriate CSF analysis were the key for a correct diagnosis.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma não Hodgkin , Tuberculose Meníngea , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Tiotepa/uso terapêutico , Tuberculose Meníngea/diagnóstico
12.
Ann Palliat Med ; 10(8): 9281-9287, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488414

RESUMO

Preoperative intra-arterial chemoembolization has been successfully applied in many malignant tumors but is rarely reported in patients with locally advanced rectal cancer (LARC). Herein we report a 69-year-old female diagnosed as rectal adenocarcinoma by endoscopic biopsy and the clinical stage was cT4aN2M0, IIIB. After computed tomography (CT) and magnetic resonance imaging (MRI) examinations, the neoplasm was considered unresectable. Then neoadjuvant chemoradiotherapy was recommended to the patient after multidisciplinary treatment. Due to the financial situation and physical condition, the patient only chose chemotherapy for preoperative treatment. During the first time of the mFOLFOX6 regimen, the patient had severe side effects of vomiting, despite tropisetron being routinely given. Then we recommended regional intra-arterial chemoembolization combined with CAPEOX regimen for conversion treatment. After intra-arterial chemoembolization with oxaliplatin and 3 months of chemotherapy with CAPEOX regimen, CT and MRI were performed again to re-evaluate the local condition. Images showed distinct remission in the tumor area, and its surrounding lymph nodes were reduced in number and volume. Also, the tumor had shrunk distinctly with a negative circumferential resection margin (CRM). We concluded that the tumor was converted into a resectable one, and the patient met the conditions for the operation. The fact indicates that it is effective in creating good operative conditions for LARC by adding intra-arterial chemotherapy to the standard treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Retais , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Resultado do Tratamento
13.
J Egypt Natl Canc Inst ; 33(1): 26, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34541625

RESUMO

BACKGROUND: The survival of pineoblastoma patients is low, particularly in infants and those with metastatic disease. This study aimed to analyze the prognostic factors affecting the outcome of Pineoblastoma in different age groups. METHODS: A retrospective study included 33 patients. Twenty-two patients older than 3 years had upfront surgery, followed by induction CSI then 6 cycles of chemotherapy. Eleven patients younger than 3 years underwent surgery, followed by induction chemotherapy then radiation therapy. Focal irradiation (54 Gy) was administrated in six patients, and CSI (23.4 Gy) with booster dose 30.6 Gy to the tumor bed in two patients followed by 4 cycles of chemotherapy. RESULTS: Patient's age showed a significant impact on the outcome (P value = 0.001 for EFS and 0.002 for OS). The metastases' presence did not impact the outcome negatively. The survival of patients with metastatic disease did not differ between age groups. However, age had a significant impact on the outcome of M0 disease, with 3-year EFS and OS of 65.3% and 74%, respectively, in the older group compared to 0% for both rates in younger patients. CSI showed a positive impact on survival. For all cases, the 3-year OS and EFS were 46.7% and 44.4%, respectively. CONCLUSIONS: A multimodality approach is needed to treat this aggressive disease. Inadequate dose intensity affected our patients' outcome negatively. A more aggressive approach using high-dose chemotherapy or CSI may be required to improve infantile pineoblastoma's dismal outcome. Focal radiotherapy is not an efficacious treatment in infants due to its high-metastatic potential. Molecular typing should be considered to label patients who need a more intensified approach.


Assuntos
Neoplasias Encefálicas , Glândula Pineal , Pinealoma , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/radioterapia , Terapia Combinada , Humanos , Lactente , Pinealoma/diagnóstico , Pinealoma/radioterapia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
14.
Lancet ; 398(10302): 759-771, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454674

RESUMO

BACKGROUND: First-line therapy for advanced oesophageal cancer is currently limited to fluoropyrimidine plus platinum-based chemotherapy. We aimed to evaluate the antitumour activity of pembrolizumab plus chemotherapy versus chemotherapy alone as first-line treatment in advanced oesophageal cancer and Siewert type 1 gastro-oesophageal junction cancer. METHODS: We did a randomised, placebo-controlled, double-blind, phase 3 study across 168 medical centres in 26 countries. Patients aged 18 years or older with previously untreated, histologically or cytologically confirmed, locally advanced, unresectable or metastatic oesophageal cancer or Siewert type 1 gastro-oesophageal junction cancer (regardless of PD-L1 status), measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, and Eastern Cooperative Oncology Group performance status of 0-1, were randomly assigned (1:1) to intravenous pembrolizumab 200 mg or placebo, plus 5-fluorouracil and cisplatin (chemotherapy), once every 3 weeks for up to 35 cycles. Randomisation was stratified by geographical region, histology, and performance status. Patients, investigators, and site staff were masked to group assignment and PD-L1 biomarker status. Primary endpoints were overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 combined positive score (CPS) of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients. This trial is registered with ClinicalTrials.gov, NCT03189719, and is closed to recruitment. FINDINGS: Between July 25, 2017, and June 3, 2019, 1020 patients were screened and 749 were enrolled and randomly assigned to pembrolizumab plus chemotherapy (n=373 [50%]) or placebo plus chemotherapy (n=376 [50%]). At the first interim analysis (median follow-up of 22·6 months), pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13·9 months vs 8·8 months; hazard ratio 0·57 [95% CI 0·43-0·75]; p<0·0001), oesophageal squamous cell carcinoma (12·6 months vs 9·8 months; 0·72 [0·60-0·88]; p=0·0006), PD-L1 CPS of 10 or more (13·5 months vs 9·4 months; 0·62 [0·49-0·78]; p<0·0001), and in all randomised patients (12·4 months vs 9·8 months; 0·73 [0·62-0·86]; p<0·0001). Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6·3 months vs 5·8 months; 0·65 [0·54-0·78]; p<0·0001), PD-L1 CPS of 10 or more (7·5 months vs 5·5 months; 0·51 [0·41-0·65]; p<0·0001), and in all randomised patients (6·3 months vs 5·8 months; 0·65 [0·55-0·76]; p<0·0001). Treatment-related adverse events of grade 3 or higher occurred in 266 (72%) patients in the pembrolizumab plus chemotherapy group versus 250 (68%) in the placebo plus chemotherapy group. INTERPRETATION: Compared with placebo plus chemotherapy, pembrolizumab plus chemotherapy improved overall survival in patients with previously untreated, advanced oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more, and overall survival and progression-free survival in patients with oesophageal squamous cell carcinoma, PD-L1 CPS of 10 or more, and in all randomised patients regardless of histology, and had a manageable safety profile in the total as-treated population. FUNDING: Merck Sharp & Dohme.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Fluoruracila/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrevida
15.
Lancet Oncol ; 22(9): 1312-1321, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34416158

RESUMO

BACKGROUND: Tyrosine kinase inhibitors have shown activity in osteosarcoma and might enhance the efficacy of chemotherapy. We aimed to determine the recommended phase 2 dose and antitumour activity of lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma. METHODS: This multicentre, open-label, multicohort, phase 1/2 trial was done at 17 hospitals in six countries. Eligible patients were aged 2-25 years, had relapsed or refractory osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Lansky play-performance score or Karnofsky performance score of 50% or higher, up to one previous VEGF or VEGF receptor-targeted therapy, and a life expectancy of at least 3 months. This study includes a combination dose-finding phase 1 part (cohort 3A) and a phase 2 combination expansion in patients with osteosarcoma (cohort 3B). Lenvatinib was administered orally at a starting dose of 11 mg/m2 per day, capped at 24 mg per day, and etoposide (100 mg/m2 per day) plus ifosfamide (3000 mg/m2 per day) were administered intravenously on days 1-3 of each 21-day cycle for a maximum of five cycles. Lenvatinib monotherapy continued after these five cycles until disease progression, toxic effects, or patient choice to discontinue. The phase 1 primary endpoint was to determine the recommended phase 2 dose by evaluating dose-limiting toxicity and the phase 2 primary endpoint was progression-free survival at 4 months. Progression-free survival was measured in the full analysis set, which included all patients enrolled for efficacy outcomes; safety was assessed in all patients who received any study drug. This study is registered with ClinicalTrials.gov, NCT02432274. FINDINGS: 30 patients were screened for enrolment into cohort 3A between May 9, 2016, and June 3, 2019, and 22 patients for enrolment into cohort 3B between Sept 13, 2018, and July 18, 2019. Eight patients from cohort 3A and two from cohort 3B were ineligible for enrolment in the study. In phase 1, dose-limiting toxicities were observed in three patients (one in the lenvatinib 11 mg/m2 combination group and two in the 14 mg/m2 combination group) and the recommended phase 2 dose was determined as lenvatinib 14 mg/m2 per day (with daily dose cap of 24 mg) and etoposide 100 mg/m2 per day plus ifosfamide 3000 mg/m2 per day administered intravenously on days 1-3 of each 21-day cycle for a maximum of five cycles. 35 patients from phase 1 (cohort 3A; n=15) and phase 2 (cohort 3B; n=20) were treated at the recommended phase 2 dose and their results were pooled. Progression-free survival at 4 months was 51% (95% CI 34-69) in 18 of 35 patients per the binomial estimate. The most common grade 3-4 treatment-emergent adverse events were neutropenia (27 [77%] of 35), thrombocytopenia (25 [71%]), anaemia (19 [54%]), and decreased white blood cell count (19 [54%]). 26 [74%] of 35 patients had serious treatment-emergent adverse events and no treatment-related deaths occurred. INTERPRETATION: Lenvatinib with etoposide plus ifosfamide shows promising antitumour activity with no new safety signals in patients with refractory and relapsed osteosarcoma. These findings warrant further investigation in an ongoing randomised phase 2 study (NCT04154189). FUNDING: Eisai and Merck Sharp & Dohme.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Osteossarcoma/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Pré-Escolar , Estudos de Coortes , Resistencia a Medicamentos Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Etoposídeo/uso terapêutico , Feminino , Humanos , Ifosfamida/uso terapêutico , Masculino , Recidiva Local de Neoplasia , Osteossarcoma/patologia , Intervalo Livre de Progressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Adulto Jovem
16.
Int J Clin Oncol ; 26(10): 1871-1880, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34453640

RESUMO

BACKGROUND: To compare irinotecan-alone, paclitaxel-alone, and each combination chemotherapy with S-1 in patients with advanced gastric cancer (AGC) that is refractory to S-1 or S-1 plus cisplatin (SP). METHODS: Patients with AGC after first-line chemotherapy with S-1 or SP, or patients during adjuvant chemotherapy or within 26 weeks after adjuvant chemotherapy completion with S-1 with confirmed disease progression were eligible. Patients were randomly divided into four groups based on treatment: irinotecan-alone (irinotecan; 150 mg/m2, day 1, q14 days), paclitaxel-alone (paclitaxel; 80 mg/m2, days 1, 8, 15, q28 days), S-1 plus irinotecan (irinotecan; 80 mg/m2, days 1, 15, S-1; 80 mg/m2, days 1-21, q35 days), and S-1 plus paclitaxel (paclitaxel; 50 mg/m2, day1, 8, S-1; 80 mg/m2, days 1-14, q21 days). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), response rate, and safety. RESULTS: From July 2008 to March 2012, 127 patients were enrolled. No difference in median OS was observed in the irinotecan vs. paclitaxel groups or in the monotherapy groups vs. the S-1 combination therapy groups. Median PFS was longer in the paclitaxel group compared with the irinotecan group (4.1 vs. 3.6 months, p = 0.035), although no difference was observed when comparing monotherapy vs. S-1 combination. The most common grade 3 to 4 hematological adverse events were neutropenia with no difference in incidence rate across the treatment groups. CONCLUSIONS: There was no difference in OS between irinotecan and paclitaxel no in OS prolongation of S-1 combination therapy in second-line chemotherapy.


Assuntos
Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Paclitaxel/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico
17.
World J Surg Oncol ; 19(1): 231, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362384

RESUMO

BACKGROUND: The clinical efficacy and safety of maintenance therapy (MT) for patients with advanced non-small cell lung cancer (NSCLC) have not been determined in the real word. This retrospective study of real-world data analyzed these issues in patients with advanced NSCLC and stable or responsive tumors after 4-6 cycles of first-line chemotherapy. METHODS: We classified 158 patients into MT (34 IIIB and 37 IV stage) and non-MT (47 IIIB and 40 IV stage) groups and then compared the clinical outcomes of progression-free survival (PFS) and overall survival (OS). The influences of maintaining chemotherapy or targeted drugs, regimens, and duration on PFS were also investigated. Prognostic factors for OS were identified by univariate and multivariate analyses. RESULTS: Among the patients, 71 received MT and 87 did not. The median PFS and OS were significantly prolonged in the MT group than non-MT group (5.6 and 14.2 vs. 2.8 and 9.8 months, respectively; both p < 0.0001). The PFS was extended when patients were maintained with targeted drugs compared with chemotherapy, > 4 cycles of chemotherapy, and targeted drugs for > 3 months (all P < 0.0001). Patients with adenocarcinoma and without distant metastasis derived a better OS benefit from MT (P = 0.041 and P = 0.037, respectively). Multivariate analysis revealed that female sex and MT were independent prognostic factors for extended OS (P = 0.039 and P < 0.0001, respectively). The major adverse events of MT comprised tolerable hematological toxicity and gastrointestinal reactions. CONCLUSIONS: MT was advantageous and tolerable for patients with advanced NSCLC, especially those with adenocarcinomas without distant metastasis who were treated with targeted drugs, which was an independent prognostic factor for OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
18.
Ann Palliat Med ; 10(7): 7847-7856, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353072

RESUMO

BACKGROUND: Endostatin and bevacizumab have been approved for the first-line treatment of advanced non-small-cell lung cancer (NSCLC) patients in China; however, the clinical outcomes for each drug combined with platinum-based doublet chemotherapy (PT-DC) have not yet been directly compared. This study sought to assess the clinical outcomes of the 2 drugs combined with PT-DC in the first-line treatment of patients with advanced lung adenocarcinoma. METHODS: This retrospective cohort study examined the clinical data of patients with metastatic or recurrent lung adenocarcinoma (LUAD) treated with endostatin or bevacizumab combined with PT-DC as the first-line treatment from October 2010 to November 2019. Propensity score matching (PSM) was performed using a 1:1 ratio nearest neighbor algorithm. The effectiveness and safety outcomes for the 2 groups were evaluated. RESULTS: A total of 202 patients were enrolled in the study. Of these, the endostatin group comprised 124 patients and the bevacizumab group comprised 78 patients; 67 pairs of patients were identified after PSM. The progression-free survival (PFS) and overall survival (OS) of patients treated with PT-DC + endostatin and PT-DC + bevacizumab were compared [(PFS: before PSM 4.8 vs. 6.5 months, P=0.741; after PSM 6.5 vs. 6.1 months, P=0.402), (OS: before PSM 21.1 vs. 39.3 months, P=0.912; after PSM 23.6 vs. 39.3 months, P=0.579)]. The objective response rates (ORRs) and disease control rates (DCRs) of the 2 groups were comparable (37.7% vs. 50.7%, P=0.094; 89.6% vs. 92.5%, P=0.545). Adverse events (AEs) ≥ grade 3 were not observed in the PT-DC + endostatin group. Three (3.8%) cases of AEs ≥ grade 3 were observed the PT-DC + bevacizumab group, comprising hypertension (n=1), proteinuria (n=1), hemoptysis (n=1). CONCLUSIONS: This retrospective analysis showed that in first-line treatments, PT-DC + endostatin and PT-DC + bevacizumab appear to produce similar anti-tumor activities in patients with metastatic or recurrent lung adenocarcinoma. PT-DC + bevacizumab tended to result in worse adverse reactions than PT-DC + endostatin.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estudos de Coortes , Endostatinas/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
19.
J Med Case Rep ; 15(1): 431, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34404459

RESUMO

BACKGROUND: It is extremely rare for primary non-Hodgkin's lymphomas to occur singly in the cranial vault. One case diagnosed as primary diffuse large B-cell lymphoma is reported, initially misdiagnosed as metastatic skull tumor, complicated with Trousseau syndrome. CASE DESCRIPTION: The patient was a 60-year-old Japanese woman with no particular previous medical history. In a head computed tomography examination for vertigo, bone destructive skull tumor covering the right frontal, parietal, and temporal bones was incidentally discovered. As positron emission tomography indicated an abnormal accumulation in the large intestine and multiple cerebral infarctions suspicious of Trousseau syndrome were observed on magnetic resonance images, a metastatic skull tumor due to colorectal cancer was first considered. However, various tumor markers were negative, and colonoscopic biopsy indicated no colorectal abnormality. After pathological examination of the resected tumor, it was diagnosed as diffuse large B-cell lymphoma. The tumor affected muscles and skin but did not develop in the brain or the dura mater. As further general examination revealed no other abnormalities, we considered that it was primary diffuse large B-cell lymphoma in the cranial vault associated with Trousseau syndrome. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and high-dose methotrexate reduced the residual lesion; coagulation abnormalities, which are frequently associated with Trousseau syndrome, also improved. CONCLUSIONS: Skull tumors can result from a variety of malignancies, and their diagnosis may be complicated with Trousseau syndrome. However, even in cases of a single lesion in the cranial vault without invasion of the central nervous system, diffuse large B-cell lymphoma should be considered as a differential diagnosis.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Neoplasias Cranianas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Neoplasias Cranianas/tratamento farmacológico , Osso Temporal , Vincristina/uso terapêutico
20.
Ann Surg Oncol ; 28(10): 5730-5741, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34342757

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer. METHODS: Based on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010-2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0). RESULTS: Of 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson-Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET. CONCLUSIONS: Although the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Hormônios , Humanos , Mastectomia , Pessoa de Meia-Idade , Resultado do Tratamento
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