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1.
Invest New Drugs ; 41(1): 115-121, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36633784

RESUMO

Thymic carcinoma is a very rare neoplasm for which no optimal chemotherapeutic regimen has been established to date. Hence, we performed this study to investigate the efficacy and safety of carboplatin plus nanoparticle albumin-bound (nab)-paclitaxel as a first-line regimen for patients with advanced thymic carcinoma. We conducted this multi-institutional retrospective cohort study of patients with advanced thymic carcinoma who had received carboplatin plus nab-paclitaxel as a first-line chemotherapy between August 2013 and December 2021. Twelve patients were included in this study and were subjected to efficacy and safety analysis. Their median age was 62 years (range, 47-74 years), and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. After a median follow-up time of 19.7 months, the overall response rate was 50%; the median progression-free and overall survival times were 8.8 months and 23.3 months, respectively. Chemotherapy-related peripheral neuropathy was observed in 2 patients (16%; each with grade 1). Other toxicities were manageable, and there were no treatment-related deaths. Carboplatin plus nab-paclitaxel as a first-line chemotherapy regimen showed good efficacy and safety in patients with advanced thymic carcinoma.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Timoma , Neoplasias do Timo , Humanos , Pessoa de Meia-Idade , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/efeitos adversos , Estudos Retrospectivos , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico
2.
Invest New Drugs ; 40(2): 430-437, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34807331

RESUMO

OBJECTIVE: The clinical outcomes of poor performance status (PS) patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib as a first-line treatment have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in chemotherapy-naive and poor PS (2 or more) patients with NSCLC harboring sensitive EGFR mutations. MATERIALS AND METHODS: We assessed the clinical effects of osimertinib as a first-line treatment for patients with poor PS NSCLC with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered osimertinib (80 mg/day) as the initial treatment. RESULTS: Sixteen patients (nine women and seven men) who were treated between August 2018 and July 2021 were included in this study; their median age was 78 years. The overall objective response rate was 56.3%. The median progression-free survival (PFS) of the entire patient population was 10.5 months and the PS score improved in 8 of 16 patients (50%). The most common adverse event was acneiform rash (42%), followed by diarrhea (36%) and paronychia (36%); none of these were of grade ≥ 3. Interstitial lung disease occurred in 2 patients (12.5%); however, no treatment-related deaths occurred. CONCLUSION: Considering the findings of this study, osimertinib appears to be an effective and safe treatment option for patients with poor PS and advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies with larger cohorts are warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Acrilamidas , Idoso , Compostos de Anilina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Mutação , Inibidores de Proteínas Quinases/efeitos adversos
3.
Cancer Manag Res ; 13: 8695-8705, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34849025

RESUMO

BACKGROUND: The clinical outcomes of elderly patients with EGFR-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations. PATIENTS AND METHODS: We assessed the clinical effects of osimertinib as a first-line treatment for elderly NSCLC patients (≥75 years of age) with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered 80 mg/day osimertinib as initial treatment. RESULTS: Forty-three patients (24 women and 19 men) with adenocarcinoma who were treated between August 2018 and July 2021 were included in this study; their median age was 79 years (range, 75-90 years). The overall objective response rate was 60.5%. The median progression-free survival (PFS) and time to treatment failure (TTF) of the entire patient population were 22.1 months and 14.6 months, respectively. The most common adverse event was rash acneiform (42%), followed by diarrhea (33%) and paronychia (28%); none of these were grades ≥3. Interstitial lung disease developed in 8 patients (18.6%); however, no treatment-related deaths occurred. Multivariate analysis identified performance status and disease stage as predictors of PFS and TTF. CONCLUSION: Considering the findings of this study and despite an observed discordance between PFS and TTF, osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies in a larger elderly population are warranted.

4.
Thorac Cancer ; 12(10): 1570-1578, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33793071

RESUMO

BACKGROUND: Galectin-3 (GAL3), a protein encoded by the LGALS3 gene, plays diverse roles in cancer initiation, progression, and drug resistance. Accordingly, high GAL3 expression in tumor cells is associated with poor prognosis in non-small cell lung cancer (NSCLC). However, the prognostic impact of GAL3 expression on patients with resected NSCLC receiving platinum-based adjuvant chemotherapy (AC) remains unclear. This study aimed to determine the prognostic significance of GAL3 expression in NSCLC patients receiving platinum-based AC. METHODS: The study included 111 patients with completely resected stages II and IIIA NSCLC who were receiving platinum-based AC. GAL3 expression in cancer cells was evaluated immunohistochemically according to H-score ("histo score), with a score of ≥170 considered as high expression. The correlation of GAL3 expression with clinicopathological characteristics and survival was subsequently evaluated. RESULTS: In survival analysis, GAL3 expression was significantly associated with recurrence-free survival (RFS) and overall survival (OS). In multivariate analysis, GAL3 expression was an independent predictive factor of RFS rather than OS. CONCLUSIONS: GAL3 expression is a reliable biomarker to predict the prognosis of completely resected NSCLC patients receiving platinum-based AC.


Assuntos
Proteínas Sanguíneas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Galectinas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
5.
Biomed Res ; 41(3): 149-159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32522932

RESUMO

NAP1L1 is a key regulator of embryonic neurogenesis but its role in lung cancer remains unexplored. In this study, we investigated the relationship between NAP1L1 expression and the clinicopathological parameters and prognosis of non-small cell lung cancer patients. To this end, the expression of NAP1L1 in tumor samples was evaluated by immunohistochemistry. NAP1L1 expression was significantly associated with reduced differentiation (P = 0.00014), higher pathological TNM stages (P < 0.00001), lymph node metastasis (P < 0.00001), intrapulmonary metastasis (P = 0.02955), lymphatic invasion (P = 0.00019), vascular invasion (P = 0.00008) and poorer prognosis (P = 0.0008) of patients with adenocarcinoma. Moreover, multivariate analyses using the Cox-proportional hazards model confirmed that NAP1L1 expression increased the risk of death after adjusting for other clinicopathological factors (HR = 2.46, 95% CI, 1.22-4.96). Furthermore, NAP1L1 expression was identified as an independent poor prognostic factor in patients with resectable stage I lung adenocarcinoma. NAP1L1-siRNA-treated lung adenocarcinoma-derived A549 cells showed significant suppression of proliferation, migration, and invasion abilities. These findings suggest that NAP1L1 may be a novel predictive and prognostic marker in lung adenocarcinoma, particularly in those with stage I of the disease.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Proteína 1 de Modelagem do Nucleossomo/genética , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Proliferação de Células , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Proteína 1 de Modelagem do Nucleossomo/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Estudos Retrospectivos , Fatores de Risco
6.
Invest New Drugs ; 38(6): 1906-1914, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32415486

RESUMO

Introduction Afatinib is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring common EGFR mutations; however, the clinicopathological factors that predict this drug's effectiveness in real-world settings remain unclear. We therefore evaluated the effectiveness of afatinib in such patients and assessed potential prognostic factors. Methods We retrospectively investigated patients with NSCLC who received first-line afatinib between July 2014 and August 2018. Variables (including sex, age, performance status, neutrophil-to-lymphocyte ratio, EGFR genotype, smoking status, clinical stage prior to treatment [stage IV vs.. postoperative recurrence], presence or absence of brain metastases, body surface area, any afatinib dose reductions, and afatinib starting dose [40 vs.. 20 or 30 mg]) were subjected to a Cox proportional hazards regression model to estimate progression-free survival (PFS). Results Forty-eight patients with a median age of 67 years were included; the objective response rate was 62.5% (30 patients). The median PFS was 14.1 months; the PFS periods were 11.8 and 15.9 months for patients receiving 40 mg versus 20-30 mg of afatinib (P = 0.41), respectively, and were 14.5 and 13.8 months for patients who required afatinib dose reduction and those who did not, respectively (P = 0.80). The PFS tended to be longer in patients without brain metastases (albeit not significantly). Ultimately, no significant predictive values for PFS were identified. Conclusions Afatinib is effective for patients with NSCLC harboring common EGFR mutations irrespective of their clinicopathological backgrounds. A direct comparison of afatinib and osimertinib in treatment-naïve patients is warranted to determine the optimal standard of care.


Assuntos
Afatinib/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Adulto , Afatinib/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos
7.
Invest New Drugs ; 38(3): 885-893, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32157598

RESUMO

Background Exon 19 deletion and L858R point mutation in exon 21 of the epidermal growth factor receptor (EGFR) are the most commonly encountered mutations in patients with non-small cell lung cancer (NSCLC) and predict better clinical outcomes following treatment with EGFR-tyrosine kinase inhibitors (TKIs). The inflammatory indicator neutrophil-to-lymphocyte ratio (NLR) in peripheral blood serves as a predictive factor for NSCLC patients treated with chemotherapy. Here, we aimed to evaluate the correlation between NLR and clinical efficacy of EGFR-TKIs in NSCLC patients harboring EGFR mutations. Methods We retrospectively collected information of 205 patients with advanced NSCLC harboring exon 19 deletion or L858R point mutation and receiving gefitinib or erlotinib. The clinical outcomes in the NSCLC patients were evaluated based on NLR level before EGFR-TKI therapy. Results The optimal cut-off value for NLR was 3.55. The response rates in the low-NLR and high-NLR groups were 69.2% and 51.5%, respectively. The median progression-free survival (PFS) in the low-NLR and high-NLR groups were 15.7 months and 6.7 months, respectively. The median overall survival (OS) in the low-NLR and high-NLR groups were 37.6 months and 19.2 months, respectively. The multivariate analysis identified performance status (PS), NLR, stage, and smoking status as independent predictors of PFS. Moreover, the PS and NLR were identified as independent predictors of OS. Conclusions NLR was a significant predictor of clinical efficacy and OS in NSCLC patients harboring EGFR mutations treated with gefitinib or erlotinib.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/uso terapêutico , Éxons/efeitos dos fármacos , Feminino , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/metabolismo , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Neutrófilos/metabolismo , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
8.
Biomed Res ; 41(1): 53-65, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32092740

RESUMO

Platinum-based adjuvant chemotherapy after complete resection has become a standard treatment for patients with stage II to IIIA non-small cell lung cancer; however, not all patients exhibit survival benefits. Therefore, the development of predictive biomarkers for selecting a subgroup of patients who may show improved survival after these treatments is important. Among the 42 proteins identified here using a proteomics analysis that were recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma who received platinum-based adjuvant chemotherapy, the tumor necrosis factor-receptor-associated protein 1 (TRAP1) was detected in patients with a short disease-free survival. TRAP1 expression was immunohistochemically analyzed in 64 patients with completely resected stage II and IIIA lung adenocarcinoma treated with platinum-based adjuvant chemotherapy. TRAP1 expression was significantly associated with higher p-TNM stage (P = 0.005) and lymph node metastasis (P = 0.017). Moreover, TRAP1 expression was significantly correlated with a shorter disease-free survival (P = 0.028). Furthermore, TRAP1-siRNA-treated LC-2/ad cells derived from lung adenocarcinoma exhibited significantly reduced proliferation and increased sensitivity to cisplatin. These results suggest that TRAP1 expression is a valuable biomarker for predicting the poor survival of platinum-based adjuvant chemotherapy in patients with resected lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/cirurgia , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/métodos , Proteínas de Choque Térmico HSP90/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Células A549 , Adulto , Idoso , Cisplatino/farmacologia , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Eletroforese em Gel Bidimensional , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteômica/métodos , RNA Interferente Pequeno/metabolismo , Estudos Retrospectivos
9.
Thorac Cancer ; 11(4): 1005-1014, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32057187

RESUMO

BACKGROUND: The standard treatment for patients with unresectable locally advanced (LA) non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT). Consolidation therapy with durvalumab after CRT demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and here we investigate the feasibility of concurrent CRT for LA-NSCLC patients based on the PACIFIC criteria. METHODS: We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA-NSCLC treated with CRT between January 2012 and June 2018. RESULTS: We analyzed a total of 108 consecutive patients who received radical thoracic radiotherapy and concurrent platinum-based chemotherapy. Of those patients, 105 (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41-317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the two-year survival rate was 63%. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (two-year survival rate: 87% vs. 41%, respectively; P = 0.001). CONCLUSIONS: Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA-NSCLC. The management of radiation pneumonitis remains a challenge following the approval of durvalumab.


Assuntos
Adenocarcinoma de Pulmão/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/mortalidade , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
10.
Thorac Cancer ; 10(11): 2142-2151, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31583841

RESUMO

BACKGROUND: Mitochondrial dysfunction contributes to many types of human disorders and cancer progression. Inner membrane mitochondrial protein (IMMT) plays an important role in the maintenance of mitochondrial structure and function. The aims of this study were to examine IMMT expression in lung adenocarcinoma and evaluate its correlation with clinicopathological parameters and patient prognosis. METHODS: IMMT expression was immunohistochemically studied in 176 consecutive lung adenocarcinoma resection tissues, and its correlations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox-proportional hazards models were used to estimate the effect of IMMT expression on survival. RESULTS: High-IMMT expression was detected in 84 of 176 (47.7%) lung adenocarcinomas. Levels were significantly correlated with advanced disease stage (stage II and III; P = 0.024), larger tumor size (>3 cm; P = 0.002), intratumoral vascular invasion (P < 0.001), and poorer adenocarcinoma patient prognosis (P = 0.002). Based on 176 patients with adenocarcinoma, multivariate analysis revealed that IMMT expression was an independent predictor of poorer survival (HR, 1.99; 95% confidence interval [CI], 1.06-3.74; P = 0.031). Further, treating A549 cells derived from lung adenocarcinoma, with IMMT siRNA resulted in significantly decreased proliferation. CONCLUSION: Here, we first demonstrated that high-IMMT expression is related to some clinicopathological parameters, and that its expression is an independent prognostic predictor of poorer survival in patients with lung adenocarcinoma; further studies are required to clarify the biological function of IMMT in lung adenocarcinoma. However, results suggest that this protein could be a novel prognostic indicator and therapeutic target.


Assuntos
Adenocarcinoma de Pulmão/cirurgia , Neoplasias Pulmonares/cirurgia , Proteínas Mitocondriais/metabolismo , Proteínas Musculares/metabolismo , Regulação para Cima , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
11.
Cancer Manag Res ; 11: 4883-4892, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213907

RESUMO

Purpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating EGFR mutation, ie, exon 19 deletion or L858R point mutation. Patients and methods: A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation. Results: A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (P=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS. Conclusion: Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.

12.
PLoS One ; 14(4): e0214599, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002722

RESUMO

PURPOSE: Oligometastasis is a state in which cancer patients have a limited number of metastatic tumors; patients with oligometastases survive longer than those with polymetastases. Extensive disease (ED)-small cell lung cancer (SCLC) is considered a systemic disease and a poor survival. This study investigated whether the concept of oligometastases is prognostic factor also applicable to patients with ED-SCLC. METHODS: We performed a retrospective study of 141 consecutive patients with ED-SCLC between 2008 and 2016. The patients were divided into four subgroups: group 1; patients with solitary metastatic site in one organ (n = 31), group 2; patients with 2-5 metastatic sites in one organ (n = 18), group 3; patients with over 6 metastases in one organ (n = 15), and group 4; patients with 2 or more metastatic organs (n = 77). RESULTS: It was identified that 49 patients with ED-SCLC had oligometastases (groups 1 + 2) and 92 had polymetastases (groups 3 + 4). The prognoses of patients with ED-SCLC and oligometastases, defined as ≤5 metastases in a single organ, were significantly superior to those of patients with polymetastases [16.0 (95% CI, 11.0-21.0) months vs. 6.9 (95% CI, 6.0-7.8) months; p<0.001]. 43 of 49 patients with ED-SCLC and oligometastases were relapsed after initial chemotherapy, and 38 (88%) experienced local recurrence. CONCLUSIONS: Patients with ED-SCLC and oligometastases may have improved survival than those with polymetastases. As oligometastatic ED-SCLC tends to recur locally, local therapy combined with systemic chemotherapy may be a treatment option.


Assuntos
Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Tomografia Computadorizada por Raios X
13.
Thorac Cancer ; 10(4): 880-889, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30821083

RESUMO

BACKGROUND: Osimertinib is recommended for non-small cell lung cancer (NSCLC) patients with EGFR mutation; however, it is unclear whether body size variables affect the efficacy of osimertinib in such patients. This study assessed the potential effect of body surface area (BSA) and body mass index (BMI) on osimertinib chemotherapy in patients with T790M-positive advanced NSCLC who progress on prior EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We conducted a prospective observational cohort study. Median BSA and BMI were used as cut-off values to evaluate the impact of body size variables on osimertinib chemotherapy. RESULTS: The median BSA and BMI of 47 patients were 1.50 m2 and 21.5 kg/m2 , respectively. Clinical outcomes did not significantly differ between the high and low BSA groups, with response rates of 59.1% and 56.0% (P = 0.83) and progression-free survival (PFS) of 7.6 and 9.1 months (P = 0.69), respectively. Similarly, there were no significant differences between the high and low BMI groups relative to response rates, which were 60.8% and 54.1% (P = 0.64), respectively, and PFS, which was 7.6 months in both groups (P = 0.38). No significant differences were observed among toxicity profiles in relation to BSA or BMI. Multivariate analysis identified better performance status, young age, and EGFR exon 19 deletion as independent favorable predictors of PFS. CONCLUSION: The efficacy of osimertinib does not significantly vary relative to body size variables of patients with T790M-positive NSCLC who progress on prior EGFR-TKIs.


Assuntos
Acrilamidas/administração & dosagem , Compostos de Anilina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Acrilamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/uso terapêutico , Índice de Massa Corporal , Superfície Corporal , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento
14.
BMC Cancer ; 19(1): 163, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30808322

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) is characterized by a high propensity for metastases and a poor prognosis irrespective of high sensitivity for initial chemotherapy. Although interstitial pneumonia (IP) is one of risk factors for lung cancer, efficacy of cytotoxic chemotherapy for patients with SCLC with IP remains unclear. Our study aims to evaluate the efficacy of systemic chemotherapy and assess risk of acute exacerbation (AE)-IP with cytotoxic drugs for extensive disease (ED)-SCLC patients with IP. METHODS: We performed a retrospective study of 192 consecutive ED-SCLC patients with IP (n = 40) and without IP (n = 152) between 2008 and 2016. RESULT: 31 of 40 ED-SCLC patients with IP and 130 of 152 patients without IP received systemic chemotherapy. The efficacy of chemotherapy in patients with IP was not inferior to that in patients without IP (overall survival [OS], 7.1 [95% confidence interval (CI): 0.2-14.0] vs. 10.0 [95% CI: 8.2-11.8] months, P = 0.57). Pretreatment serum levels of lactate dehydrogenase (LDH; 651.7 ± 481.0 vs. 301.4 ± 110.7 U/mL, P = 0.01) and C-reactive protein (CRP; 8.9 ± 9.6 vs. 1.8 ± 1.8 U/mL, P = 0.008) were correlated with developed AE-IP in the ED-SCLC patients with IP. CONCLUSION: Systemic chemotherapy was effective even in ED-SCLC patients with IP. However, the risk of developed AE-IP that was high in patients with IP and should be evaluated using serum LDH and CRP levels before initial chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Progressão da Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , L-Lactato Desidrogenase/sangue , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Risco , Carcinoma de Pequenas Células do Pulmão/complicações , Carcinoma de Pequenas Células do Pulmão/mortalidade , Análise de Sobrevida , Resultado do Tratamento
15.
Cancer Manag Res ; 10: 7013-7019, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588105

RESUMO

BACKGROUND: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. PATIENTS AND METHODS: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. RESULTS: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59-83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. CONCLUSION: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD.

16.
Cancer Manag Res ; 10: 6039-6047, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30538553

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) is typically categorized according to disease extent as limited or extensive, and utility of the 8th TNM classification, recommended for lung cancer staging, which demonstrates a strong association with non-small-cell lung cancer (NSCLC) management, remains unclear. METHODS: This retrospective study included 277 consecutive SCLC patients treated at a single institution between 2008 and 2016. RESULTS: According to the currently used two-stage system, 186 (65.7%) of the patients were classified as having extensive disease (ED)-SCLC. Among the ED-SCLC patients, ten (5.3%), 38 (20.4%), 32 (17.2%), and 106 (57.0%) were categorized into stages M0, M1a, M1b, and M1c, respectively, according to the 8th TNM classification. There was a significant difference in overall survival based on the M descriptors: 15.8 (95% CI 9.4-22.2) months in the M1b group vs 7.3 (95% CI 5.7-8.9) months in the M1c group (P<0.001). Multivariate analysis showed that in addition to the known prognostic factors such as performance status, serum albumin, and lactate dehydrogenase, M descriptor was a prognostic factor (HR 1.95, 95% CI 1.38-2.77; P<0.001). CONCLUSION: The 8th TNM classification has a prognostic value in SCLC. Similarly to NSCLC, treatment approaches should be considered on the basis of the 8th TNM classification, especially stage IVA separate from stage IVB in ED-SCLC patients.

17.
Intern Med ; 57(21): 3149-3152, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29877291

RESUMO

We herein report the case of a 52-year-old man with stage IV lung adenocarcinoma. The patient was negative for epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule-associated protein-like 4 (EML4) /anaplastic lymphoma kinase (ALK) rearrangement. He was treated with nivolumab as a third-line chemotherapy. After four cycles of nivolumab treatment, a partial response was observed in the brain and at the primary tumor site. Nivolumab treatment has been continued for 11 months without progression. Immunohistochemistry revealed that the programmed death-ligand 1 (PD-L1) expression was 0% (according to the tumor proportion score). Our case indicates that the efficacy of programmed cell death 1 inhibitors is not solely predicted by the PD-L1 status, and that immune checkpoint inhibitors might be effective for the treatment of central nervous system metastasis.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/secundário , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/análise , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/patologia , Nivolumabe/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Progressão da Doença , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade
18.
Oncology ; 95(2): 109-115, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29698957

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKIs) therapy has been recognized as the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, resistance to EGFR-TKIs has been observed in certain subpopulations of these patients. We aimed to evaluate the impact of smoking history on the efficacy of EGFR-TKIs. METHODS: The records of patients (n = 248) with NSCLC harboring activating EGFR mutations who were treated with gefitinib or erlotinib at our institution between March 2010 and June 2016 were retrospectively reviewed, and the treatment outcomes were evaluated. RESULTS: The overall response rate and median progression-free survival (PFS) were 59.7% and 10.7 months, respectively. The overall response rate was significantly higher in the ex- and nonsmokers than in the current smokers (64.6 vs. 51.1%, p = 0.038). PFS also differed significantly between the current smokers and the ex- and nonsmokers (12.4 vs. 7.4 months, p = 0.016). Multivariate analysis identified smoking history as an independent predictor of PFS and overall survival. CONCLUSION: The clinical data obtained in this study provide a valuable rationale for considering smoking history as a predictor of the efficacy of EGFR-TKI in NSCLC patients harboring activating EGFR mutations.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/uso terapêutico , Feminino , Gefitinibe , Humanos , Masculino , Pessoa de Meia-Idade , Quinazolinas/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
19.
Invest New Drugs ; 35(5): 642-648, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28631097

RESUMO

Background Previous study indicated that an optional anti-cancer drug for the treatment of small-cell lung cancer (SCLC) is amrubicin. However, no prospective studies have evaluated amrubicin in chemo-naive elderly or poor-risk patients with SCLC. Therefore, this study aimed to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly or poor-risk patients with extensive-disease SCLC (ES-SCLC). Methods Patients with chemotherapy-naive ES-SCLC received multiple cycles of 40 mg/m2 amrubicin for 3 consecutive days every 21 days. The primary endpoint was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results Between March 2011 and August 2015, 36 patients were enrolled in this study. Each patient received a median of four treatment cycles (range, 1-6 cycles). ORR was 52.8% [95% confidence interval (CI), 37-69%]. The median PFS and OS periods were 5.0 months (95% CI, 3.4-6.6 months) and 9.4 months (95% CI, 5.2-13.6 months), respectively. Neutropenia was the most common grade 3 or 4 adverse event (69.4%), with febrile neutropenia developing in 13.9% of patients. No treatment-related death occurred. At the time of starting second-line chemotherapy, 19 of 22 patients (86%) had significantly improved or maintained their performance status (PS) relative to their PS at the time of starting amrubicin monotherapy as first-line chemotherapy (P = 0.027). Conclusions The results of the present study suggest that amrubicin could be considered as a viable treatment option for chemotherapy-naive elderly or poor-risk patients with ES-SCLC (Clinical trial registration number: UMIN000011055 www.clinicaltrials.gov ).


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco
20.
Asian Pac J Cancer Prev ; 17(7): 3249-53, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27509958

RESUMO

BACKGROUND: Pemetrexed monotherapy has come to be recognized as one of the standard secondline therapies for advanced nonsquamous nonsmall cell lung cancer (NSCLC). However, there have been no reports of studies that have evaluated the efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon 19 deletion or an L858R point mutation. MATERIALS AND METHODS: The records of nonsquamous NSCLC patients harboring an EGFR mutation who received pemetrexed monotherapy as a second or later line of chemotherapy at Kitasato University Hospital between March 2010 and October 2015 were retrospectively reviewed, and the treatment outcomes were evaluated. RESULTS: The overall response rate and progressionfree survival time (PFS) of the 53 patients with nonsquamous NSCLC were 15.1% and 2.3 months, respectively. There were significant differences between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs. 3.3 months) of the exon 19 deletion group and the L858R point mutation group, and a multivariate analysis identified type of EGFR mutation as well as performance status (PS) as independent predictors of PFS. CONCLUSIONS: The clinical data obtained in this study provided a valuable rationale for considering type of EGFR mutation as well as non squamous histology as predictors of the efficacy of pemetrexed monotherapy.


Assuntos
Adenocarcinoma/genética , Neoplasias Encefálicas/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação/genética , Recidiva Local de Neoplasia/genética , Pemetrexede/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Genótipo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Taxa de Sobrevida
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