RESUMO
BACKGROUND: This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. METHODS: In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin. RESULTS: Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade ≥3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. CONCLUSION: Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imidazóis/administração & dosagem , Indazóis/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Axitinibe , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Feminino , Humanos , Imidazóis/farmacocinética , Indazóis/farmacocinética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Paclitaxel/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Resultado do TratamentoRESUMO
BACKGROUND: Tumor spread through air spaces (STAS) in lung adenocarcinoma is a novel mechanism of invasion. STAS has been proposed as an independent predictor of poor prognosis. The aim of this study was to evaluate the correlations between STAS status and other clinicopathologic variables and to assess the prognostic implications of STAS and the distance from the edge of the tumor to the farthest STAS in patients with resected lung adenocarcinoma. MATERIAL AND METHODS: This is a single-institution retrospective observational study. We included all patients with resected lung adenocarcinoma from January 2017 to December 2018 at La Paz University Hospital. The cut-off for the distance from the edge of the tumor to the farthest STAS was 1.5 mm and was assessed by the area under the receiver operating characteristic curve. RESULTS: A total of 73 patients were included. STAS was found in 52 patients (71.2%). Histological grade 3 (P = 0.035) and absence of lepidic pattern (P = 0.022) were independently associated with the presence of STAS. The median recurrence-free survival (RFS) was 48.06 months [95% confidence interval (CI) 33.58 months to not reached]. STAS-positive patients had shorter median RFS [39.23 months (95% CI 29.34-49.12 months)] than STAS-negative patients (not reached) (P = 0.04). STAS-positive patients with a distance from the edge of the tumor to the farthest STAS ≥1.5 mm had an even shorter median RFS [37.63 months (95% CI 28.14-47.11 months)]. For every 1 mm increase in distance, the risk of mortality increased by 1.26 times (P = 0.04). CONCLUSIONS: Histological grade 3 and absence of lepidic pattern were independently associated with the presence of STAS. STAS was associated with a higher risk of recurrence. The distance from the edge of the tumor to the farthest STAS also had an impact on overall survival.
Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologiaRESUMO
OBJECTIVE: To characterise current management of chemotherapy-induced nausea and vomiting in Spain, as well as professional adherence to antiemetic guidelines. MATERIALS AND METHODS: Retrospective observational study. A multicenter has been designed including 360 patient case files from 18 hospitals. The involvement of pharmacists and nurses was studied, and also indicators of structure, process, and selected outcomes previously recruited from antiemetic guidelines. RESULTS: We found 94.4% of hospitals used a written protocol for managing chemotherapy-induced nausea and vomiting and only 44.4% had educational programs for patients regarding this. Patients were prescribed antiemetic prophylactic treatment for delayed emesis in varying degree between highly and moderately emetogenic chemotherapy (77.8% and 58.9%, respectively). Dexamethasone was the most prescribed antiemetic drug for patients receiving highly and moderately emetogenic chemotherapy (98.3% and 90%, respectively), followed by ondansetron (68.9% and 95%, respectively). Nursing was more involved than pharmacy units in evaluating emetic risk factors in patients (64.7% vs 21.4%), and tracking symptom onset (88.2% vs 57.1%) and adherence to treatment (94.1% vs 28.6%). Pharmacy units were more involved than nursing in choosing the antiemetic treatment (78.6% vs 47%). CONCLUSIONS: Although antiemetic guidelines were used by all hospitals, there were differences in management of chemotherapy-induced nausea and vomiting. Increased education directed towards patients and oncology professionals is needed to improve adherence.
Assuntos
Antieméticos , Vômito , Antieméticos/uso terapêutico , Humanos , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Ondansetron/uso terapêutico , Espanha , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controleRESUMO
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor, with a poor prognosis. MPM needs to find prognostic factors of survival. We provided the management of patients with MPM and sought to determine whether pre-treatment levels of derived neutrophil-to-lymphocyte ratio (dNLR) as well as PD-L1 expression were reliable prognostic factors of survival. METHODS: We conducted a single-institution retrospective study, including all patients with MPM treated at La Paz University Hospital between December 2009 and March 2018. Baseline disease, demographics, clinical data, treatment characteristics and complete blood cell counts were collected. We examined dNLR at baseline and data for PD-L1 expression were analyzed in tumor cells by immunohistochemistry. RESULTS: We included 25 patients. The median overall survival (OS) was 15.7 months (95% CI 11.3-20.0). 5 patients had a dNLR greater than 3 (20%). Patients with a dNLR greater than 3 had shorter median OS (8.5 months), than patients with a dNLR less than 3 (17.0 months), with statistically significant differences (p = 0.038). Ten patients (40%) had positive PD-L1 expression (≥ 1%). Patients with positive PD-L1 expression had shorter median OS (8.5 months) than patients with negative PDL1 expression (15.7 months), but without statistically significant association (p = 0.319). CONCLUSION: The survival data obtained in our sample are consistent with those previously reported. Pretreatment levels of dNLR greater than 3 and positive PD-L1 expression could be significant prognostic factors for poor survival in patients with MPM. Further and prospective studies are needed to explore this relationship and to derive definitive conclusions.
Assuntos
Antígeno B7-H1/metabolismo , Linfócitos/citologia , Mesotelioma Maligno/sangue , Neutrófilos/citologia , Neoplasias Pleurais/sangue , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Contagem de Células Sanguíneas , Feminino , Humanos , Imuno-Histoquímica , Masculino , Mesotelioma Maligno/tratamento farmacológico , Mesotelioma Maligno/mortalidade , Mesotelioma Maligno/patologia , Pessoa de Meia-Idade , Pemetrexede/uso terapêutico , Compostos de Platina/uso terapêutico , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/mortalidade , Neoplasias Pleurais/patologia , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.
Assuntos
Mesotelioma Maligno/diagnóstico , Mesotelioma Maligno/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Antineoplásicos/uso terapêutico , Amianto/toxicidade , Carcinógenos/toxicidade , Terapia Combinada/métodos , Procedimentos Cirúrgicos de Citorredução , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Oncologia , Mesotelioma Maligno/etiologia , Mesotelioma Maligno/patologia , Estadiamento de Neoplasias , Pemetrexede/uso terapêutico , Compostos de Platina/uso terapêutico , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/patologia , Radioterapia/métodos , Sociedades Médicas , Espanha , Vinorelbina/uso terapêutico , GencitabinaRESUMO
PURPOSE: Proper monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with antiemetics is crucial for cancer patients. This study aimed to evaluate the use of antiemetics for the treatment of highly emetogenic chemotherapy (HEC) including carboplatin in the real-world setting in Spain. METHODS: A representative panel of cancer specialists was asked to collect information about the antiemetic treatments provided to patients receiving chemotherapy. Records formed part of the Global Oncology Monitor© database (Ipsos Healthcare, London, UK). Chemotherapy data were extrapolated using Ipsos Healthcare's projection methodology. RESULTS: A total of 73 experts were finally included. Data from 9519 patients, estimated to be representative of 202,084 patients, were collected. HEC (and carboplatin-based chemotherapy) was administered to 73,118 (36%) patients, cisplatin-based therapy being the most frequent treatment (n = 34,649, 47.38%). Neurokinin-1 receptor antagonists (NK1RAs) alone or in combination were used as prophylaxis for CINV in 14,762 (20%) patients, while the combination of NK1RA with 5-hydroxytryptamine-3 receptor antagonist (5-HT3RAs) and dexamethasone as recommended by the international guidelines was used in 5849 (8%) patients only. No antiemetic prophylaxis was administered to 8.46% of the patients receiving HEC (n = 6189). Physicians classified cisplatin-, anthracycline-cyclophosphamide (AC-), and carboplatin-based regimens as HEC in 63%, 22% and 4% of the cases, respectively. CONCLUSIONS: The use of NK1RA-containing regimens for CINV prevention in patients treated with HEC was less than expected, suggesting poor adherence to international antiemetic guidelines.
Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controle , Antraciclinas/efeitos adversos , Carboplatina/efeitos adversos , Cisplatino/efeitos adversos , Consenso , Ciclofosfamida/efeitos adversos , Bases de Dados Factuais , Dexametasona/uso terapêutico , Fidelidade a Diretrizes , Pesquisas sobre Atenção à Saúde/métodos , Humanos , Náusea/induzido quimicamente , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Antagonistas do Receptor 5-HT3 de Serotonina/uso terapêutico , EspanhaRESUMO
BACKGROUND: Cancer and cancer therapies have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in cancer patients receiving immunotherapy and ascertain its prognostic utility. MATERIALS AND METHODS: We conducted a single-institution retrospective study, including all cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). RESULTS: We selected 229 patients. VTE occurred in 16 of 229 patients (7%). VTE occurred more frequently in patients with lung cancer followed by melanoma. Female sex and melanoma were independently associated with an increased risk of VTE. 12 of 16 VTE (75%) were symptomatic. Progressive disease to immunotherapy [HR 31.60 (95% CI 11.44-87.22), p = 0.00], lung cancer [HR 2.55 (95% CI 1.34-4.86), p = 0.00] and melanoma [HR 2.42 (1.20-4.86), p = 0.01] were independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS [HR 1.33 (95% CI 0.63-2.80), p = 0.44]. CONCLUSIONS: The incidence of VTE in cancer patients receiving immunotherapy in our study appeared to be similar to the incidence previously reported in other series of cancer patients treated with systemic therapies. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions.
Assuntos
Imunoterapia/efeitos adversos , Neoplasias/terapia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The efficacy and safety of capecitabine and bevacizumab in elderly patients with metastatic colorectal cancer (mCRC) considered unsuitable for receiving first-line chemotherapy with an irinotecan or oxaliplatin-based combination were assessed in a phase II, open, multicentre, uncontrolled study. METHODS: Treatment consisted of capecitabine 1250 mg m(-2) (or 950 mg m(-2) for patients with a creatinine clearance of 30-50 ml min(-1)) twice daily on days 1-14 and bevacizumab (7.5 mg kg(-1)) on day 1 every 3 weeks. RESULTS: A total of 59 patients aged >or=70 years with mCRC were enrolled. In an intention-to-treat analysis, the overall response rate was 34%, with 71% of patients achieving disease control. Median progression-free survival and overall survival were 10.8 months and 18 months, respectively. In all, 32 patients (54%) had grade 3/4 adverse events (AEs), the most common being hand-foot syndrome (19%), diarrhoea (9%) and deep venous thrombosis (7%). Four patients died because of treatment-related AEs. A relationship was detected between creatinine clearance Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
, Neoplasias Colorretais/tratamento farmacológico
, Idoso
, Idoso de 80 Anos ou mais
, Anticorpos Monoclonais/administração & dosagem
, Anticorpos Monoclonais/efeitos adversos
, Anticorpos Monoclonais Humanizados
, Bevacizumab
, Capecitabina
, Neoplasias Colorretais/mortalidade
, Desoxicitidina/administração & dosagem
, Desoxicitidina/efeitos adversos
, Desoxicitidina/análogos & derivados
, Intervalo Livre de Doença
, Feminino
, Fluoruracila/administração & dosagem
, Fluoruracila/efeitos adversos
, Fluoruracila/análogos & derivados
, Humanos
, Estimativa de Kaplan-Meier
, Masculino
RESUMO
BACKGROUND: The purpose of this study was to identify clinical and pathological parameters to improve prediction of disease-free survival (DFS) and overall survival (OS) in patients treated with neoadjuvant chemoradiotherapy for rectal cancer. METHODS: Between July 1995 and May 2007, 148 patients with primary rectal adenocarcinoma received neoadjuvant chemoradiotherapy followed by mesorectal excision. Preoperative treatment included various protocols, UFT and leucovorin (28%) and oxaliplatin-based chemotherapy (72%). Clinical and pathological variables were evaluated in relation to patient outcomes. RESULTS: Thirteen percent of patients achieved a complete pathologic response. No response or minimal response as defined by Dworak (Tumor Regression Grade 0/1) was observed in 30 patients (20%). At a median follow-up of 37 months, the 3-year DFS and OS were 64% and 83%, respectively. Pre-treatment serum carcinoembryonic antigen (CEA) level = 2.5 ng/ml was associated with higher DFS (74 vs. 53%; p = 0.018), higher complete pathologic responses (21 vs. 9%; p = 0.05), and less recurrences (24 vs. 44%; p = 0.014). CONCLUSION: The data suggest that a CEA level = 2.5 ng/ml might be a predictor not only of tumor response, as has been suggested before, but also of DFS. This finding could be useful in the future to predict individual risk and to develop more aggressive or alternative strategies.
Assuntos
Antígeno Carcinoembrionário/sangue , Terapia Neoadjuvante , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Recidiva , Resultado do TratamentoRESUMO
Signalling pathways that emerge from EGFR activation are critical in colon cancer (CC) biology. Its targeting with specific drugs has opened a new window in the treatment of this disease. In this regard, monoclonal antibodies (mAb) have evidenced a high degree of efficiency opposed to the uselessness of tyrosine-kinase inhibitors. Cetuximab is the mAb that has evidenced most activity in CC. After its initial approval as an irinotecan-resistance reversal agent, cetuximab has demonstrated its efficiency from the first line to heavily pretreated patients. In the first line, its addition may increase response rate to chemotherapy, improving liver metastases resection rate. Another promising approach has been suggested from combination schedules with bevacizumab. Panitumumab has been recently approved for CC. Although there is limited clinical experience, the latest data have confirmed its activity in heavily pretreated patients resulting in a clinical benefit vs. best support care. In spite of the clinical benefits, adverse events and the high sanitary cost derived from these drugs force the selection of patients with the highest probability of benefit. At the moment, when EGFR expression evidenced by immunohistochemistry has no value, skin toxicity and, fundamentally, K-Ras mutations may hint at critical information for confirmatory prospective studies.
Assuntos
Neoplasias do Colo/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Cetuximab , Neoplasias do Colo/etiologia , Neoplasias do Colo/genética , Receptores ErbB/análise , Receptores ErbB/genética , Receptores ErbB/fisiologia , Amplificação de Genes , Genes ras , Humanos , Hibridização in Situ Fluorescente , Mutação , Panitumumabe , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Non-small-cell lung cancer (NSCLC) represents the most frequent and therapy-refractive sub-class of lung cancer. Improving apoptosis induction in NSCLC represents a logical way forward in treating this tumor. Cisplatin, a commonly used therapeutic agent in NSCLC, induces activation of N-terminal-c-Jun kinase (JNK) that, in turn, mediates induction of apoptosis. In analysing surgical tissue samples of NSCLC, we found that expression of MKP1/CL100, a negative regulator of JNK, showed a strong nuclear staining for tumor cells, whereas, in normal bronchial epithelia, MKP1 was localized in the cytoplasm as well as in nuclei. In the NSCLC-derived cell lines H-460 and H-23, we found that MKP1 was constitutively expressed. Expressing a small-interfering RNA (siRNA) vector for MKP1 in H-460 cells resulted in a more efficient activation by cisplatin of JNK and p38 than in the parental cells, and this correlated with a 10-fold increase in sensitivity to cisplatin. A similar response was also observed in H-460 and H-23 cells when treated with the MKP1 expression inhibitor RO-31-8220. Moreover, expression of a siRNA-MKP2, an MKP1-related phosphatase, had no effect on H-460 cell viability response to cisplatin. Tumors induced by H-460 cells expressing MKP1 siRNA grew slower in nu(-)/nu(-) mice and showed more susceptibility to cisplatin than parental cells, and resulted in an impaired growth of the tumor in mice. On the other hand, overexpression of MKP1 in the H-1299 NSCLC-derived cell line resulted in further resistance to cisplatin. Overall, the results showed that inhibition of MKP1 expression contributes to a slow down in cell growth in mice and an increase of cisplatin-induced cell death in NSCLC. As such, MKP1 can be an attractive target in sensitizing cells to cisplatin to increase the effectiveness of the drug in treating NSCLC.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/fisiologia , Proliferação de Células , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Inibidores do Crescimento/fisiologia , Proteínas Imediatamente Precoces/fisiologia , Neoplasias Pulmonares/patologia , Fosfoproteínas Fosfatases/fisiologia , Proteínas Tirosina Fosfatases/fisiologia , Adulto , Idoso , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fosfatase 1 de Especificidade Dupla , Feminino , Inibidores do Crescimento/antagonistas & inibidores , Inibidores do Crescimento/biossíntese , Humanos , Proteínas Imediatamente Precoces/antagonistas & inibidores , Proteínas Imediatamente Precoces/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Fosfoproteínas Fosfatases/antagonistas & inibidores , Fosfoproteínas Fosfatases/biossíntese , Proteína Fosfatase 1 , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Proteínas Tirosina Fosfatases/biossíntese , RNA Interferente Pequeno/farmacologiaRESUMO
Lung cancer is a frequent cause of cancer-related deaths in the world. There is no valid screening process and this limits its detection to the late stages, with consequently high mortality rates. Volatile organic compounds (VOC) are chemical compounds (mainly the products of cell catabolism) found as gases in the human breath. Different methods have been developed to analyse VOCs and to compare them in healthy subjects and lung cancer patients. In this review, we summarise the different techniques used to analyse VOC. Many reports have been published with promising results similar to those achieved with accepted screening methods such as mammography. These methods show good perspectives on lung cancer screening.
Assuntos
Testes Respiratórios/métodos , Neoplasias Pulmonares/diagnóstico , Humanos , Neoplasias Pulmonares/metabolismoRESUMO
Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future (AU)
Assuntos
Humanos , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapia , Estadiamento de Neoplasias , Sociedades Médicas , EspanhaRESUMO
Purpose Proper monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with antiemetics is crucial for cancer patients. This study aimed to evaluate the use of antiemetics for the treatment of highly emetogenic chemotherapy (HEC) including carboplatin in the real-world setting in Spain. Methods A representative panel of cancer specialists was asked to collect information about the antiemetic treatments provided to patients receiving chemotherapy. Records formed part of the Global Oncology Monitor© database (Ipsos Healthcare, London, UK). Chemotherapy data were extrapolated using Ipsos Healthcares projection methodology. Results A total of 73 experts were finally included. Data from 9519 patients, estimated to be representative of 202,084 patients, were collected. HEC (and carboplatin-based chemotherapy) was administered to 73,118 (36%) patients, cisplatin-based therapy being the most frequent treatment (n = 34,649, 47.38%). Neurokinin-1 receptor antagonists (NK1RAs) alone or in combination were used as prophylaxis for CINV in 14,762 (20%) patients, while the combination of NK1RA with 5-hydroxytryptamine-3 receptor antagonist (5-HT3RAs) and dexamethasone as recommended by the international guidelines was used in 5849 (8%) patients only. No antiemetic prophylaxis was administered to 8.46% of the patients receiving HEC (n = 6189). Physicians classified cisplatin-, anthracycline-cyclophosphamide (AC-), and carboplatin-based regimens as HEC in 63%, 22% and 4% of the cases, respectively. Conclusions The use of NK1RA-containing regimens for CINV prevention in patients treated with HEC was less than expected, suggesting poor adherence to international antiemetic guidelines (AU)
Assuntos
Humanos , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controle , Fidelidade a Diretrizes , Pesquisas sobre Atenção à Saúde , EspanhaRESUMO
Hemolytic disease by cold-reacting antibodies is a rare form of hemolytic anemia. In most cases a subjacent cause is found. This disease is generally related with reactive lymphoproliferative processes (infections by the Epstein-Barr virus and cytomegalovirus) or uncontrolled lymphoproliferative disorders (lymphomas, Waldenström disease, chronic lymphatic leukemia). The presence of high titers of cryoagglutinins have recently been described in patients infected by the human immunodeficiency virus (HIV); however, clinical manifestation as hemolytic anemia is very rare. A 37 year old male diagnosed with infection by HIV, non Hodgkin's lymphoma of Burkitt type non convoluted cells, chronic hepatopathy by the B and C virus, Brouet type III cryoglobulinemia and hemolytic anemia by cold-reacting antibodies is herewith described. This multiple association is exceptional as is the important clinical repercussion of the hemolytic anemia derived from the high titers and above all the wide thermic interval of the cryoagglutinin present. Finally, the relation of cryoagglutinin with each of these entities, the concomitant presence of cryoglobulins and the evolution of the titers of the same with the chemotherapy treatment administered for the lymphoma is analyzed.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Anemia Hemolítica Autoimune/complicações , Linfoma de Burkitt/complicações , Adulto , Humanos , MasculinoRESUMO
The clinical case of a 73-years old male who was admitted for diarrhea and loss of weight is presented. Barium enema and colonoscopy demonstrated small size polyps in the sigmoid colon, one of which had a histologic diagnosis of adenocarcinoma. Abdominal examination detected a mass in the mesohypogastrium which did not appear to be related to the previous findings. CAT and intestinal transit confirmed a second tumor in the small bowel with the histologic diagnosis of a resected specimen being melanoma.
Assuntos
Adenocarcinoma , Pólipos do Colo , Neoplasias do Íleo , Melanoma , Neoplasias Primárias Múltiplas , Neoplasias do Colo Sigmoide , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Idoso , Pólipos do Colo/diagnóstico por imagem , Pólipos do Colo/cirurgia , Seguimentos , Humanos , Neoplasias do Íleo/diagnóstico por imagem , Neoplasias do Íleo/cirurgia , Masculino , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Neoplasias do Colo Sigmoide/diagnóstico por imagem , Neoplasias do Colo Sigmoide/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
Although many cancers initially respond to cisplatin (CDDP)-based chemotherapy, resistance frequently develops. Insulin-like growth factor-binding protein-3 (IGFBP-3) silencing by promoter methylation is involved in the CDDP-acquired resistance process in non-small cell lung cancer (NSCLC) patients. Our purpose is to design a translational-based profile to predict resistance in NSCLC by studying the role of IGFBP-3 in the phosphatidyl inositol 3-kinase (PI3K) signaling pathway. We have first examined the relationship between IGFBP-3 expression regulated by promoter methylation and activation of the epidermal growth factor receptor (EGFR), insulin-like growth factor-I receptor (IGFIR) and PI3K/AKT pathways in 10 human cancer cell lines and 25 NSCLC patients with known IGFBP-3 methylation status and response to CDDP. Then, to provide a helpful tool that enables clinicians to identify patients with a potential response to CDDP, we have calculated the association between our diagnostic test and the true outcome of analyzed samples in terms of cisplatin IC50; the inhibitory concentration that kills 50% of the cell population. Our results suggest that loss of IGFBP-3 expression by promoter methylation in tumor cells treated with CDDP may activate the PI3K/AKT pathway through the specific derepression of IGFIR signaling, inducing resistance to CDDP. This study also provides a predictive test for clinical practice with an accuracy and precision of 0.84 and 0.9, respectively, (P=0.0062). We present a biomarker test that could provide clinicians with a robust tool with which to decide on the use of CDDP, improving patient clinical outcomes.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Metilação de DNA , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/deficiência , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fosforilação , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/genética , Receptor IGF Tipo 1/genética , Transdução de Sinais , TransfecçãoRESUMO
Patients with metastatic Colorectal Cancer (mCRC), in which primary tumors are KRAS mutated, have no response to anti-EGFR therapy. However, less than half of mCRC patients with KRAS wild-type primary tumors respond to anti-EGFR therapy. Other downstream effectors of the EGFR pathway are being analyzed to fine-tune KRAS predictive value. However, as the primary tumor is the tissue of analysis that determines the use of anti-EGFR therapy in advanced disease, a high concordance in the status of these effectors between primary tumors and related metastases is required. We analyzed the concordances of downstream EGFR effectors in tumoral pairs of primaries and related metastases in a series of KRAS wild-type patients. One hundred seventeen tumoral pairs from patients with CRC were tested for KRAS mutational status. The level of concordance in the presence of KRAS mutations was 91% between the primary tumor and related metastases. The 70 pairs with KRAS wild-type primary tumors were further analyzed for BRAF and PIK3CA mutational status and for EGFR, PTEN and pAKT expression, and the number of concordant pairs was 70 (100%), 66 (94%), 43 (61%), 46 (66%) and 36 (54%), respectively. Our findings suggest that the mutational status of KRAS, BRAF and PIK3CA in the primary tumor is an adequate surrogate marker of the status in the metastatic disease. On the other hand, the immunohistochemical analysis of EGFR, PTEN and pAKT showed a much higher degree of discordance between primaries and related metastases.
Assuntos
Neoplasias Colorretais/metabolismo , Receptores ErbB/metabolismo , Metástase Neoplásica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Genes ras , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
The discovery of anaplastic lymphoma kinase (ALK) rearrangements in a subset of patients with nonsmall- cell lung cancer (NSCLC) and its potential blockage by specific inhibitors such as crizotinib has been one of the latest advances in the treatment of this disease. In this article, we will review the most important clinical aspects of ALK alterations in NSCLC patients and the pending questions to answer: the most effective means of diagnosing ALK-rearranged NSCLC, and efficacy, toxicity profile and potential mechanisms of resistance to crizotinib.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Proteína Tirosina Quinases/genética , Quinase do Linfoma Anaplásico , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Crizotinibe , Humanos , Neoplasias Pulmonares/enzimologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismoRESUMO
Background Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor, with a poor prognosis. MPM needs to find prognostic factors of survival. We provided the management of patients with MPM and sought to determine whether pre-treatment levels of derived neutrophil-to-lymphocyte ratio (dNLR) as well as PD-L1 expression were reliable prognostic factors of survival. Methods We conducted a single-institution retrospective study, including all patients with MPM treated at La Paz University Hospital between December 2009 and March 2018. Baseline disease, demographics, clinical data, treatment characteristics and complete blood cell counts were collected. We examined dNLR at baseline and data for PD-L1 expression were analyzed in tumor cells by immunohistochemistry. Results We included 25 patients. The median overall survival (OS) was 15.7 months (95% CI 11.320.0). 5 patients had a dNLR greater than 3 (20%). Patients with a dNLR greater than 3 had shorter median OS (8.5 months), than patients with a dNLR less than 3 (17.0 months), with statistically significant differences (p = 0.038). Ten patients (40%) had positive PD-L1 expression (≥ 1%). Patients with positive PD-L1 expression had shorter median OS (8.5 months) than patients with negative PDL1 expression (15.7 months), but without statistically significant association (p = 0.319). Conclusion The survival data obtained in our sample are consistent with those previously reported. Pretreatment levels of dNLR greater than 3 and positive PD-L1 expression could be significant prognostic factors for poor survival in patients with MPM. Further and prospective studies are needed to explore this relationship and to derive definitive conclusions (AU)