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1.
Support Care Cancer ; 32(10): 647, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39251506

RESUMO

PURPOSE: Taxanes are widely used chemotherapeutic agents that frequently cause nail changes and have a significant impact on patients' quality of life. Despite the prevalence of taxane-induced nail toxicity, limited data are available regarding evidence-based management strategies for the prevention or treatment of taxane-induced nail changes. Therefore, we aimed to gain insights into the prevention, treatment, and evaluation of nail changes in patients with cancer in Japan by conducting a questionnaire survey of physicians, pharmacists, and nurses involved in oncology treatment. METHODS: The questions addressed prophylactic methods, evaluation practices, and treatment approaches for various nail disorders. The questionnaires were distributed on March 1, 2022, with a response deadline of December 1, 2022. RESULTS: Of the 120 questionnaires distributed, 88 (73.3%) were returned, and all of them were analyzed. The respondents included 69 physicians (32 oncologists, 26 breast surgeons, 6 dermatologists, 3 obstetricians/gynecologists, 1 gastroenterological surgeon, and 1 urologist), 9 pharmacists, and 10 nurses. Prophylactic measures included moisturizing (58.0%), protection (42.0%), cooling therapy (37.5%), and cleanliness (33.0%). Approximately 70% of the respondents used the Common Criteria for Adverse Events (CTCAE), while approximately 30% did not use a specific evaluation method. Opinions regarding treatment with antimicrobial or corticosteroid ointments varied; however, all severe cases were referred by dermatologists. CONCLUSION: Our survey revealed that the management of chemotherapy-induced nail changes varies in clinical practice in Japan. These findings emphasize the need for standardized management strategies and further research.


Assuntos
Antineoplásicos , Doenças da Unha , Taxoides , Humanos , Japão , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Doenças da Unha/induzido quimicamente , Inquéritos e Questionários , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , Masculino , Neoplasias/tratamento farmacológico , Qualidade de Vida , Pessoal de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade
2.
Hepatol Res ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990762

RESUMO

AIM: Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population. METHODS: From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders. RESULTS: In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis. CONCLUSIONS: In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry with the number UMIN000043798.

3.
Acta Med Okayama ; 78(1): 63-70, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38419316

RESUMO

The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma.


Assuntos
Antineoplásicos , Carcinoma , Quinolinas , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Antineoplásicos/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico
4.
Chemotherapy ; 69(1): 45-48, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37820606

RESUMO

Vascular endothelial growth factor receptor tyrosine kinase inhibitors are known to cause perforation as one of their severe side effects, and postoperative and postradiation therapy are known risk factors. However, there are few studies on perforation following tumor shrinkage. A 78-year-old woman with postoperative recurring left collecting duct carcinoma of the right hilar lymph nodes and mediastinum underwent eight courses of nivolumab plus cabozantinib, resulting in tumor shrinkage. Three days after the last administration, she developed fever and cough and was hospitalized for right lobar pneumonia. The patient received long-term antibiotics for bronchial fistula with the destruction of the bronchial wall and secondary lung abscess. When using nivolumab plus cabozantinib combination therapy for a tumor with bronchial invasion, physicians should be aware of bronchial perforation as the tumor shrinks.


Assuntos
Anilidas , Carcinoma de Células Renais , Neoplasias Renais , Piridinas , Feminino , Humanos , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Nivolumabe/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico
5.
Cancer Diagn Progn ; 3(5): 605-608, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37671312

RESUMO

Background/Aim: Synchronous colorectal cancer, which occurs in approximately 4.8-8.4% of all colorectal cancers, has a genetic profile with a higher rate of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and microsatellite instability-high than solitary colorectal cancer. However, little information is available on heterogeneity among tumor lesions because of difficulty in performing genetic tests in all lesions in clinical practice. Case Report: A 44-year-old man presented with multiple recurrent lung metastases 42 months after the endoscopic resection of early stage synchronous ascending and sigmoid colon cancers. The genetic testing of sigmoid colon cancer tissue samples, their state being more advanced than that of ascending colon cancer, revealed a v-Ki-ras 2 Kirsten rat sarcoma viral oncogene homolog mutation (G13C) and BRAF wild type. However, the tumor was refractory to initial chemotherapy and rapidly progressed to new liver metastases. Therefore, we suspected that there may be biological heterogeneity between the primary sigmoid colon lesion and liver metastases. Next, we performed next-generation sequencing on circulating tumor DNA from the patient's plasma (Foundation One Liquid CDx®), which revealed the V600E mutation of BRAF, suggesting that there was genetic heterogeneity among the synchronized primary lesions, one of which was responsible for the chemo-refractory rapid-growing liver metastases. Conclusion: Genetic profiling with liquid biopsy at the time of recurrence and metastasis may be useful in patients with multiple synchronous cancers because there is less heterogeneity between primary and metastatic sites.

6.
Int J Clin Oncol ; 28(10): 1333-1342, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37418141

RESUMO

Chronic kidney disease (CKD) is one of the most disabling disorders with significant comorbidity and mortality. Incidence and prevalence of CKD in cancer survivors are remarkably high in both adults and pediatric patients. The reasons for this high incidence/prevalence are multifold but kidney damage by cancer itself and cancer treatment (pharmacotherapy/surgery/radiation) are the main reasons. Since cancer survivors commonly have significant comorbidities, risk of cancer recurrence, limited physical function or life expectancy, special attentions should be paid when considering the treatment of CKD and its complications. Especially, shared decision-making should be considered when selecting the renal replacement therapies with as much information/facts/evidence as possible.

7.
Cancer Chemother Pharmacol ; 92(3): 235-240, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37380798

RESUMO

PURPOSE: Rhabdomyolysis, which is primarily characterized by serum creatine kinase (CK) elevation, is a potentially fatal disease, and it can occur in a variety of etiologies, including drug-induced. Cabozantinib is one of the standard treatments for patients with renal cell carcinoma (RCC). This retrospective case series aimed to investigate the frequency of cabozantinib-induced CK elevation and rhabdomyolysis, and to reveal their detailed clinical features. METHODS: To investigate the frequency of cabozantinib-induced serum CK elevation and rhabdomyolysis, we retrospectively reviewed the clinical information and laboratory data of the patients with advanced RCC who received cabozantinib monotherapy at our institution from April 2020 to April 2023. Data were retrieved from the electronic medical records and the RCC database of our institution. Primary endpoint of the current case series was the frequency of CK elevation and rhabdomyolysis. RESULTS: Sixteen patients were retrieved form the database and 13 were included in the case series (excluded by clinical trial enrollment [n = 2] and short-term administration [n = 1]). Eight (61.5%) patients among them experienced serum CK elevation, including five patients who were classified into grade 1. CK elevation occurred a median of 14 days after initiation of cabozantinib. Two patients with grade 2 or 3 of CK elevation developed rhabdomyolysis with muscle weakness and/or acute kidney injury. CONCLUSIONS: CK elevation may frequently happen during cabozantinib treatment, and in most cases, it may be asymptomatic and may not be clinically problematic. However, medical providers should be aware that symptomatic CK elevations suggestive of rhabdomyolysis may occasionally occur.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Rabdomiólise , Humanos , Estudos Retrospectivos , Carcinoma de Células Renais/tratamento farmacológico , Rabdomiólise/induzido quimicamente , Creatina Quinase , Neoplasias Renais/tratamento farmacológico
8.
Int J Clin Oncol ; 28(5): 637-643, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36976431

RESUMO

Anticancer drug therapy for cancer is developing rapidly, including molecular-targeted drugs and immune checkpoint inhibitors that are used in clinical settings in addition to conventional cytotoxic drugs. In daily clinical practice, clinicians sometimes encounter situations in which the effects of these chemotherapeutic agents are considered unacceptable in high-risk patients with liver or renal dysfunction, those undergoing dialysis and older adults. There is no clear evidence regarding anticancer drugs administration to patients with renal dysfunction. However, there are indications for dose setting based on the theory of the renal function responsible for drug excretion and past administration experience. This review outlines anticancer drugs' administration in patients with renal dysfunction.


Assuntos
Antineoplásicos , Nefropatias , Neoplasias , Humanos , Idoso , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Diálise Renal , Nefropatias/tratamento farmacológico , Nefropatias/induzido quimicamente
9.
IJU Case Rep ; 6(2): 144-146, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36875003

RESUMO

Introduction: The peripheral nervous system is one of the target organs of immune-related adverse events. Peripheral facial nerve palsy, also called Bell's palsy, which is induced by immune checkpoint inhibitors, is quite rare, and its clinical features are not well known. Case presentation: A man with renal cell carcinoma who received rechallenging immune checkpoint inhibitor therapy developed unilateral facial palsy and was diagnosed with Bell's palsy. He did not have any severe immune-related adverse events during his previous immune checkpoint inhibitor treatment. Corticosteroid therapy was immediately initiated, and his facial palsy symptoms promptly improved. Conclusion: Physicians should be aware that Bell's palsy can occur as an immune-related adverse event. Additionally, careful observation is necessary during rechallenge with immune checkpoint inhibitors, even in patients who did not have previous immune-related adverse events.

10.
Intern Med ; 62(21): 3163-3166, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36948620

RESUMO

Aortitis is a rare adverse event associated with granulocyte colony-stimulating factor (G-CSF). Contrast-enhanced computed tomography (CECT) is widely used to diagnose G-CSF-associated aortitis. However, the usefulness of gallium scintigraphy for the diagnosis of G-CSF-associated aortitis is unknown. We herein report a set of pre- and post-treatment gallium scintigrams of a patient with G-CSF-associated aortitis. During the diagnosis, gallium scintigraphy revealed hot spots on the arterial walls that appeared inflamed on CECT. Both the CECT and gallium scintigraphy findings disappeared. Gallium scintigraphy can be a supportive diagnostic tool for G-CSF-associated aortitis, especially in patients with an impaired renal function or allergy to iodine contrast.


Assuntos
Aortite , Gálio , Humanos , Aortite/diagnóstico por imagem , Aortite/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Cintilografia , Tomografia Computadorizada por Raios X
11.
Gan To Kagaku Ryoho ; 49(11): 1200-1204, 2022 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-36412020

RESUMO

Chronic kidney disease(CKD)associated with cancer and its treatment affects life after cancer treatment. There is inconclusive opinion on whether CKD treatment in survivors after cancer treatment needs special care differently than in the general population with CKD. Several topics were discussed by nephrologists, urologists and medical oncologists, pediatricians, pharmaceutical specialists, and others based on the results of a literature search, and the consensus was documented in the "Clinical Practice Guidelines for the Management for Kidney Injury During Anticancer Drug Therapy, 2022". The prevalence of CKD among adult cancer survivors is reported to be 4-7%. The characteristics include(1)elderly and physically impaired patients(, 2)a high risk of cancer recurrence, and(3)frequently cancer treatment-related CKD. Although there are no cancer survivor-specific indications or contraindications in the selection of renal replacement therapy, renal transplantation is often preferred in pediatric cancer survivors. It was determined that it is not appropriate to recommend or not recommend the administration of erythropoietin stimulating agents for renal anemia in cancer survivors based on a systematic review and discussion between panelists. When used in individual cases, its application should be well examined and consideration should be given to avoiding high hemoglobin level and to monitoring for cancer development.


Assuntos
Sobreviventes de Câncer , Neoplasias , Oncologistas , Insuficiência Renal Crônica , Adulto , Idoso , Humanos , Criança , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Sobreviventes , Consenso , Neoplasias/complicações , Neoplasias/terapia
12.
Eur J Cancer ; 166: 279-286, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35349925

RESUMO

BACKGROUND: The mainstream first-line chemotherapy for advanced/recurrent gastric cancer (ARGC) is combination therapy including platinum-based agents. With the progressive aging of the society, the incidence of gastric cancer in elderly patients is increasing. However, elderly patients cannot tolerate these agents because of renal dysfunction or low quality of life. The KSCC1701 study explored the efficacy and safety of S-1 + ramucirumab in elderly patients with ARGC. PATIENTS AND METHODS: Chemotherapy-naive patients aged ≥70 years with ARGC were eligible. Patients received S-1 (40-60 mg twice daily for 4 weeks in 6-week cycles) and ramucirumab (8 mg/kg every 2 weeks) until disease progression. The primary end-point was the 1-year overall survival (OS) rate. The anticipated lower threshold of 1-year survival was set at 40% in light of previous S-1-based regimens. The secondary end-points included progression-free survival (PFS), OS, the overall response rate (ORR) and safety. RESULTS: Between September 2017 and November 2019, 48 patients (34 men and 14 women) were enrolled in this study. The median patient age was 77.5 years, and all patients had a performance status of 0 (n = 20) or 1 (n = 28). The 1-year OS rate was 65.2%, which met the primary end-point. The median survival time and median PFS were 16.4 and 5.8 months, respectively. The ORR was 41.9%. The most frequent grade 3/4 (≥15%) adverse events were neutropenia, anorexia and anaemia. CONCLUSION: Considering these findings, S-1 + ramucirumab appears to be an excellent treatment option for elderly patients with ARGC. (250 words). This trial has been registered with the Japan Registry of Clinical Trials Registry under the number jRCTs071180066.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/etiologia , Qualidade de Vida , Neoplasias Gástricas/tratamento farmacológico , Ramucirumab
13.
HPB (Oxford) ; 24(8): 1245-1251, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35216869

RESUMO

BACKGROUND: The effect of bevacizumab plus mFOLFOX6 on downsizing of liver metastases for curative resection has not been well assessed for patients with advanced colorectal liver metastases (CRLMs). This multicenter phase II trial aimed to examine the efficacy and safety of bevacizumab plus mFOLFOX6 for advanced CRLMs harboring mutant-type KRAS. METHODS: Patients with advanced CRLMs (tumor number of ≥5 and/or technically unresectable) harboring mutant-type KRAS were included. Surgical indication was evaluated every 4 cycles of bevacizumab plus mFOLFOX6. Liver resection was planned if the CRLMs were resectable. The primary endpoint was R0 resection rate. The secondary endpoints included overall survival (OS), recurrence-free survival, progression-free survival, and safety. RESULTS: Between 2013 and 2017, 29 patients from six centers were registered. The rates of complete and partial responses were 0% and 62.1%, respectively. R0 and R1 resections were performed in 19 and 1 patient, respectively (R0 resection rate: 65.5%). No mortality occurred. During the median follow-up of 30.7 months, the 3-year OS rate for all the patients was 64.4% with the median survival of 49.1 months. CONCLUSION: For advanced CRLMs harboring mutant-type KRAS, bevacizumab plus mFOLFOX6 achieved a high R0 resection rate, leading to favorable survival.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , Compostos Organoplatínicos/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética
14.
Anticancer Res ; 41(6): 2841-2848, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34083274

RESUMO

BACKGROUND/AIM: Expression of human leukocyte antigen (HLA) class I and II and CD74, which functions as a chaperone of MHC class II, play essential roles in T-cell recognition. The aim of this study was to elucidate the association between the HLAs and CD74, and their correlation with the infiltrated immune cells in renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively investigated the expression of HLA-A/B/C, HLA-DR, and CD74 in 38 patients with advanced RCC (T3/T4), and evaluated their correlations with CD4 and CD8-positive T-cell infiltration using immunohistochemistry. RESULTS: The expression of HLA-A/B/C, HLA-DR, and CD74 on cancer cells was observed in 37, 20, and 31 patients, respectively. The density of CD8- and CD4-positive T cells showed a positive correlation with HLA-DR expression. The density of CD4-positive lymphocytes was significantly associated with CD74 expression. CONCLUSION: The expression of HLA-DR, rather than CD74, on cancer cells was potentially associated with the anti-cancer immune microenvironment.


Assuntos
Antígenos de Diferenciação de Linfócitos B/imunologia , Carcinoma de Células Renais/imunologia , Antígenos HLA-DR/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Neoplasias Renais/imunologia , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
BMC Cancer ; 21(1): 588, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022838

RESUMO

BACKGROUND: A self-help workbook is expected to support cancer patients to cope with physical and psychosocial distress, to facilitate communication with medical staff, and to improve quality of life (QOL). We conducted a randomized controlled trial to evaluate the effectiveness of a self-help workbook intervention on QOL and survival. METHODS: From June 2014 to March 2015, patients with breast, colorectal, gastric, and lung cancer receiving outpatient chemotherapy were randomized into an intervention group (n = 100) or control group (n = 100). Intervention group participants received workbooks originally made for this study, read advice on how to cope with distress, and filled out questionnaires on the workbooks periodically. EORTC QLQ-C30 was evaluated at baseline, at 12 weeks, and at 24 weeks. The primary endpoint was Global Health Status / QOL scale (GQOL). RESULTS: No significant interaction was observed between the intervention and time in terms of GQOL or any of the functional scales. Among the 69 patients who continued cytotoxic chemotherapy at 24 weeks, the intervention was significantly associated with improved emotional functioning scores (P = 0.0007). Overall survival was not significantly different between the two groups. CONCLUSIONS: Self-help workbook intervention was feasible in cancer patients receiving chemotherapy. Although the effect of the intervention was limited, a post-hoc subset analysis suggested that the intervention may improve emotional functioning among patients who receive long-term cytotoxic chemotherapy. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000012842 . Registered 14 January 2014.


Assuntos
Adaptação Psicológica , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Navegação de Pacientes/métodos , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Educação de Pacientes como Assunto/métodos , Angústia Psicológica , Resultado do Tratamento
16.
Pancreas ; 49(4): 493-497, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32282761

RESUMO

The focus of the review is on roles of autophagy and pancreatic secretory trypsin inhibitor (PSTI), an endogenous trypsin inhibitor, in trypsinogen activation in acute pancreatitis. Acute pancreatitis is a disease in which tissues in and around the pancreas are autodigested by pancreatic digestive enzymes. This reaction is triggered by the intrapancreatic activation of trypsinogen. Autophagy causes trypsinogen and cathepsin B, a trypsinogen activator, to colocalize within the autolysosomes. Consequently, if the resultant trypsin activity exceeds the inhibitory activity of PSTI, the pancreatic digestive enzymes are activated, and they cause autodigestion of the acinar cells. Thus, autophagy and PSTI play important roles in the development and suppression of acute pancreatitis, respectively.


Assuntos
Autofagia/fisiologia , Pancreatite/metabolismo , Inibidor da Tripsina Pancreática de Kazal/fisiologia , Tripsinogênio/metabolismo , Células Acinares/patologia , Animais , Catepsina B/metabolismo , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Ativação Enzimática , Glicoproteínas/deficiência , Humanos , Lisossomos/enzimologia , Camundongos , Camundongos Knockout , Chaperonas Moleculares/fisiologia , Pancreatite/enzimologia , Pancreatite/patologia , Proteínas Secretadas pela Próstata , Dobramento de Proteína , Proteólise , Vesículas Secretórias/enzimologia , Fator de Transcrição CHOP/deficiência , Inibidor da Tripsina Pancreática de Kazal/deficiência
17.
Anticancer Res ; 39(12): 6895-6901, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810959

RESUMO

BACKGROUND: Lenvatinib, a newly developed oral multi-tyrosine kinase inhibitor, has amazing potential in the multidisciplinary treatment of advanced or metastatic hepatocellular carcinoma. Thrombocytopenia is a serious adverse event that causes drug dose reduction or withdrawal. Partial splenic embolization is currently being used as a non-surgical treatment for thrombocytopenia caused by various pharmacotherapies. CASE REPORT: Partial splenic embolization was performed for three patients with hepatocellular carcinoma receiving lenvatinib therapy with/without transarterial chemoembolization. Partial splenic embolization was advantageous for various situations, including the induction of lenvatinib for patients with thrombocytopenia, application of lenvatinib after multiple transarterial chemoembolization using cisplatin and radiotherapy, and re-administration of lenvatinib after lenvatinib therapy-induced thrombocytopenia. In all cases, lenvatinib therapy was completed without need for cessation due to thrombocytopenia. CONCLUSION: We strongly recommend the new concept of combining partial splenic embolization and lenvatinib therapy for hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Trombocitopenia/terapia , Idoso , Embolização Terapêutica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Baço , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
18.
Anticancer Res ; 39(10): 5695-5701, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570469

RESUMO

Large tumor size and arterioportal shunt are poor prognostic factors for hepatocellular carcinoma. Lenvatinib is a novel and potent multi-tyrosine kinase inhibitor developed in Japan. A 66-year-old woman with hepatocellular carcinoma and untreated hepatitis C was referred to our hospital. She was judged as unresectable and was treated with four sessions of transarterial chemoembolization; however, the therapeutic effect was unsatisfactory because of major arterioportal shunt. Lenvatinib was sequentially administered for 4 months. Thereafter, we observed tumor shrinkage, complete disappearance of arterioportal shunt, and obvious improvement in liver function. A curative conversion hepatectomy was successfully accomplished. The extremely high levels of tumor markers almost normalized; the pretreatment levels were 1,008,021 ng/ml for alpha-fetoprotein. At 1 year after the primary treatment, the patient has not experienced recurrence. To our knowledge, this is the first case of a patient with initially unresectable hepatocellular carcinoma with arterioportal shunt who underwent conversion hepatectomy after multidisciplinary treatment, including lenvatinib.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , alfa-Fetoproteínas/metabolismo
19.
Oncologist ; 24(3): 327-337, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30425180

RESUMO

BACKGROUND: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. MATERIALS AND METHODS: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). RESULTS: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p = .07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p = .134 for RR; interaction test, p = .102 for PFS and p = .003 for OS) and 8q24.2 (Fisher's exact test, p = .179 for RR; interaction test, p = .144 for PFS and p = .002 for OS). CONCLUSION: Chromosome 8q24.1-q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. IMPLICATIONS FOR PRACTICE: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1-p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab.


Assuntos
Bevacizumab/uso terapêutico , Biomarcadores/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Hibridização Genômica Comparativa/métodos , Irinotecano/uso terapêutico , Oxaliplatina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/farmacologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Irinotecano/farmacologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Oxaliplatina/farmacologia , Prognóstico , Análise de Sobrevida
20.
Cancer Control ; 25(1): 1073274818789361, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30032643

RESUMO

Lenvatinib is a small-molecule tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR1-3), fibroblast growth factor receptor (FGFR1-4), platelet-derived growth factor receptor α (PDGFRα), stem cell factor receptor (KIT), and rearranged during transfection (RET). These receptors are important for tumor angiogenesis, and lenvatinib inhibits tumor angiogenesis by inhibiting function of these receptors. Phase I trials of lenvatinib were conducted at the same time in Japan, Europe, and the United States, and tumor shrinkage effects were observed in thyroid cancer, endometrial cancer, melanoma, renal cell carcinoma, sarcoma, and colon cancer. Lenvatinib is a promising drug that has shown therapeutic effects against various solid tumors. Adverse events, such as hypertension, proteinuria, diarrhea, and delayed wound healing, can occur with lenvatinib treatment. Managing these adverse events is also important for the use of lenvatinib. In this mini-review article, we outline the current state, toxicity, and future prospects of lenvatinib toward thyroid cancer, hepatocellular carcinoma, renal cell carcinoma, and lung cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Antineoplásicos/farmacologia , Ensaios Clínicos Fase I como Assunto , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Incidência , Terapia de Alvo Molecular/métodos , Neoplasias/irrigação sanguínea , Neovascularização Patológica/tratamento farmacológico , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteinúria/induzido quimicamente , Proteinúria/epidemiologia , Quinolinas/farmacologia , Resultado do Tratamento
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