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BACKGROUND: Germline pathogenic variants in the E-cadherin gene CDH1 cause hereditary diffuse gastric cancer (HDGC), which is an autosomal dominant cancer syndrome, accounting for 1-3% of all gastric cancers. HDGC harboring a CDH 1 variant is extremely rare in Japan. METHOD: In this study we report the clinical courses of three cases with HDGC from a single Japanese family. RESULTS: The proband exhibited advanced and metastatic gastric cancer, and was found to have a previously reported heterozygous frameshift variant in CDH1 (NM_004360.3:c.1009_1010del:p.Ser337Phefs*12). Five at-risk relatives underwent presymptomatic molecular testing after careful genetic counseling, and three were molecularly diagnosed as positive for the variant. Esophagogastroduodenoscopy was performed in these relatives revealing abnormal small pale mucosal patches, small ulcerative lesion and no abnormal findings. Moreover, random and targeted biopsies were compatible with pathological diagnosis of HDGC in the three cases, all of which underwent total prophylactic gastrectomy. CONCLUSION: It is critical for the assessment and management of HDGC patients to be actively offered a multidisciplinary and familial-oriented approach. Notably, genetic screening in suspected individuals and familial members is a determining piece for a higher detection rate and the identification of clinical relevant mutations in both low and high-incidence gastric cancer countries.
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A 29-year-old woman with chronic, prolonged pustular psoriasis was admitted to our hospital because of high-grade fever and a systemic skin rash. General examination revealed a whole-body skin rash and superficial lymphadenopathy. Peripheral blood examination showed unclassified cells positive for CD3, CD4, and T-cell receptor αß, and negative for CD20 and CD56. Soon after administration, she developed acute respiratory failure and required artificial ventilation. Bronchoalveolar lavage fluid showed increased numbers of eosinophils and abnormal lymphocytes of the same phenotype in peripheral blood and skin. She was diagnosed with eosinophilic pneumonia, and her respiratory failure was improved by corticosteroid therapy. Based on the histological findings of skin, lymph node, and bone marrow biopsies, a diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), with positivity for CC chemokine receptor 4 was made. She received chemotherapy followed by allogeneic stem cell transplantation, which resulted in complete remission of her PTCL-NOS. She remained alive and disease-free 6 years later. This is the first reported case of PTCL-NOS developing during the clinical course of pustular psoriasis. The clinical manifestations of PTCL-NOS are complex, but an accurate diagnosis and appropriate therapy may produce a good clinical outcome in patients with PTCL-NOS.
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Exantema , Linfoma de Células T Periférico , Psoríase , Eosinofilia Pulmonar , Adulto , Feminino , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/tratamento farmacológico , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Receptores CCR4RESUMO
BACKGROUND: This study was performed to clarify the treatment outcome of patients with primary mediastinal germ cell tumors (PMGCTs), focusing on the clinical manifestations and management during definitive therapy and long-term follow-up. METHODS: In this study, we retrospectively reviewed the medical records of patients with PMGCTs treated at Shinshu University School of Medicine, and examined the clinical profiles and treatment outcomes of 22 patients (mean age of 29 years) with primary mediastinal GCTs treated at our hospital between 1983 and 2019. RESULTS: Five patients were diagnosed with pure seminoma and 17 had nonseminomatous GCT. A total of 21 patients were treated with cisplatin-based chemotherapy and 15 patients (68.2%) underwent thoracic surgery after chemotherapy. Although all cases of nonseminomatous GCT were negative for tumor markers after cisplatin-based chemotherapy, two cases showed variable GCT cells and two had somatic components (angiosarcoma and rhabdomyosarcoma) in resected specimens. Three relapsed soon after surgery. Growing teratoma syndrome developed during chemotherapy in four cases. Urgent thoracic surgery was performed in three patients, but one case was inoperable. The calculated 10-year overall survival rates were 100% in mediastinal seminoma and 64.7% in NSGCT. During follow-up, second non-GCT malignancies developed in three patients (colon cancer, 190 months; thyroid cancer, 260 months; non-small cell lung cancer, 250 months after the initial chemotherapy) and one patient with primary mediastinal seminoma was associated with multiple type I endocrine tumors. CONCLUSIONS: Our experiences demonstrated that long-term survival and/or cure can be achieved with adequate chemotherapy followed by local surgical treatment even in patients with mediastinal GCTs. However, the clinical manifestations and biological behaviors during and/or after chemotherapy were complex and varied. In addition, the development of secondary malignancies should be taken into consideration for long-term follow-up. Clinicians should be aware of the various clinical features and secondary malignancies in primary mediastinal GCTs.
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Neoplasias do Mediastino/epidemiologia , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Due to its rarity, little is known about the clinical presentations and responses to systemic chemotherapies in advanced and/or metastatic cases of paratesticular liposarcoma. CASE PRESENTATION: Here, we report the case of a 75-year-old Japanese man with giant paratesticular liposarcoma. Imaging studies revealed a 26 cm tumor in his right scrotum and lung metastases at presentation. He underwent radical orchiectomy followed by systemic chemotherapies. Pathological findings of the resected primary tumor confirmed a dedifferentiated liposarcoma. He then started chemotherapy treatment with gemcitabine plus docetaxel. His disease status was stable for 1 year. Eribulin was used for second-line chemotherapy. He had a relapse at 5 months after eliburin and died at 22 months after diagnosis. CONCLUSION: Early diagnosis and curative radical surgery are important for treatment of paratesticular liposarcoma. However, a giant paratesticular liposarcoma could cause metastases, and systemic chemotherapy may be helpful for prolonging survival in patients with metastatic paratesticular liposarcoma.
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Lipossarcoma/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Neoplasias Testiculares/patologia , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Docetaxel/uso terapêutico , Evolução Fatal , Humanos , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/terapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Orquiectomia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/terapia , GencitabinaRESUMO
Herein we report two cases of advanced and/or metastatic salivary duct carcinoma that relapsed after standard first-line chemotherapy. As overexpression of human epidermal growth factor receptor 2 (HER2) (3+) was observed by immunohistochemistry, the patients were treated with trastuzumab plus paclitaxel. One patient showed a complete response lasting over 2.5 years after the commencement of therapy; however, the other patient had no response to trastuzumab combined therapy. Dual fluorescence in situ hybridization was performed after the initiation of chemotherapy; the first case was positive for HER2 gene amplification, while the second case was negative. Our experiences suggest that therapy with HER2 blockers should be considered as options for treatment of HER2-positive salivary duct carcinoma. However, HER2 protein overexpression and gene amplification should be investigated further as therapeutic biomarkers.
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BACKGROUND: Fluorine-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake in primary lesions has been well studied, but little information is available about metastatic bone lesions in patients with lung cancer. The present study was performed to evaluate the relationships between metastatic bone FDG uptake and clinical parameters in patients with lung cancer. METHODS: FDG uptake was evaluated as the maximum standardized uptake (SUVmax) value of each targeted bone lesion, and the bone to primary lesion ratio of SUVmax (B/P ratio) was calculated. Forty-nine patients (27 men and 22 women) with a diagnosis of lung cancer (small cell lung cancer [SCLC], n = 7; non-small cell lung cancer [NSCLC], n = 42) with bone metastasis, and a total of 185 bone metastatic lesions were evaluated. RESULTS: The SUVmax in bone and the B/P ratio were significantly higher in patients with pain and subsequent development of skeletal-related events than in those without pain or skeletal-related events, respectively. In addition, the SUVmax in metastatic bone lesions and the B/P ratio in SCLC were significantly lower than those in NSCLC, despite similar FDG uptake in the primary tumor. CONCLUSION: Our findings suggest that FDG-PET evaluation in metastatic bone lesions could be useful to predict initial pain and subsequent clinical outcomes of local bone status in initially diagnosed lung cancer patients with bone metastasis. In addition, our results suggest that there could be histological differences in the biological activity of bone metastatic lesions in lung cancer, especially between SCLC and NSCLC.
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Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Dor do Câncer/epidemiologia , Fluordesoxiglucose F18/administração & dosagem , Neoplasias Pulmonares/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/metabolismoRESUMO
Gastric cancer frequently spreads to the regional lymph nodes, liver and lungs following surgery or late in the clinical course. However, an initial clinical presentation of bone metastasis in gastric cancer patients is relatively rare. The current study presents two cases of gastric cancer diffusely metastasized to the spinal vertebrae and with a single metastasis to the trapezium, respectively. The initial presentations were an increased alkaline phosphatase level without any symptoms associated with bone metastasis in the first case and a swelling in the right carpometacarpal joint of the thumb in the second case. These clinical manifestations are also extremely rare in gastric cancer with bone metastasis. The study emphasizes that a diagnosis of gastric cancer should be considered in patients with increased alkaline phosphatase without clinical symptoms or with a single bone metastasis.
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Pulmonary neuroendocrine tumors are rare, and there have been very few reports regarding optimal chemotherapeutic regimens. Two molecular targeted agents, everolimus and sunitinib, have recently been shown to provide an additional treatment benefit for pulmonary neuroendocrine tumors. However, little information is available regarding the usefulness of streptozocin chemotherapy. Here, we encountered a case of relapsed and refractory mediastinal atypical carcinoid tumor associated with multiple endocrine neoplasia type 1 for various cytotoxic and molecular targeted agents. The patient showed a good response to streptozocin monotherapy. We describe the case and review streptozocin chemotherapy in patients with pulmonary neuroendocrine tumors.
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A 63-year-old woman underwent thyroidectomy for papillary thyroid adenocarcinoma and cervical lymph node resection. Pathological analyses revealed the presence of signet cell carcinoma in a resected lymph node, which were apparently different from the pathological findings of thyroid carcinoma. No evidence of a primary tumor could be found elsewhere despite detailed examinations, including esophagogastroduodenoscopy, colonoscopy, capsule endoscopy, CT scan, and fluorodeoxyglucose-positron emission tomography. Two and half years later, the patient developed multiple bone metastases and the pathological findings confirmed the presence of signet cell carcinoma. The primary origin remained undetermined. Metastatic signet ring cell carcinoma of unknown primary origin is extremely rare.
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Adenocarcinoma/cirurgia , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/terapia , Linfonodos/cirurgia , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/terapia , Neoplasias da Glândula Tireoide/cirurgia , Idoso , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Doenças Raras/diagnóstico , Doenças Raras/terapia , Tireoidectomia , Resultado do TratamentoRESUMO
A 58-year-old woman with a histologically confirmed diagnosis of vulvar extramammary Paget's disease (EMPD) was referred to our hospital due to locally advanced and relapsed EMPD. The patient had undergone surgical resection three times for relapsed vulvar EMPD over a period of 12 years, but developed locally advanced and unresectable EMPD. As pathological examination indicated that the lesion was positive for human epidermal growth factor receptor 2 (HER2) on immunohistochemical staining, the patient was treated with trastuzumab plus paclitaxel. The primary tumor mass and lymph node metastasis regressed successfully with combined trastuzumab and paclitaxel therapy, and the disease has been stable for >2 years after the initiation of treatment. These observations suggest that HER2 status must be determined in patients with advanced and/or metastatic extramammary Paget's disease and therapy with HER2 inhibitors should be considered as an option for the treatment of HER2-positive EMPD.
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A 63-year-old female patient who had undergone cholecystectomy for inflammatory myofibroblastic tumor (IMT) in the gallbladder was referred to our hospital. The patient's disease relapsed, involving the pancreas, and was diagnosed as inoperable IMT 13 months after the cholecystectomy. The patient failed to respond to steroid and non-steroidal anti-inflammatory drug therapy, but subsequently exhibited a good response to vinorelbine and methotrexate combination chemotherapy. Little information is currently available on the efficacy of chemotherapy for adult-onset IMT. The present case suggests that chemotherapy with vinorelbine and methotrexate is a viable therapeutic option for adult patients with unresectable IMT.
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Malignant peripheral nerve sheath tumor (MPNST) in the thorax is an extremely rare disease, and half of all cases of MPNST are associated with neurofibromatosis type I. Sporadic intrathoracic MPNST is difficult to diagnose and treat. Because of the rarity of intrathoracic MPNST, the optimal method of diagnosis and the efficacy of chemotherapy are unknown. Herein, we present a case of inoperable mediastinal MPNST, in which the diagnosis was immunohistochemically made by the loss of H3K27me3 expression in a transbronchial needle biopsy specimen. The patient showed a good response to doxorubicin plus ifosfamide chemotherapy. The present case highlights that MPNST should be included in the differential diagnosis of non-posterior mediastinum thoracic lesions, and that appropriate diagnosis and treatment for intrathoracic MPNST should be considered in patients with a thoracic mass.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Histonas/metabolismo , Neoplasias do Mediastino/tratamento farmacológico , Neurilemoma/tratamento farmacológico , Regulação para Baixo , Doxorrubicina/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Ifosfamida/uso terapêutico , Neoplasias do Mediastino/metabolismo , Pessoa de Meia-Idade , Neurilemoma/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Several studies indicated that plasma L-carnitine (LC) levels are significantly decreased during chemotherapy or chemoradiation and that LC supplementation can improve the fatigue score in some cancer patients. However, the LC levels in end-stage cancer patients treated only with palliative care remained unclear. The present study was performed to examine the plasma LC levels of terminally ill and hospitalized patients. METHODS: Twenty-one terminally ill cancer patients in our hospital, with expected survival of several months, were enrolled in the present study. Blood samples were taken for measurement of total, free, and acyl-LC. These values were compared with those in 22 chemo-naive cancer patients scheduled to receive cisplatin-containing chemotherapy as first-line therapy. We examined the relationships with body mass index, albumin and CRP levels, the presence of general fatigue, and body weight loss. RESULTS: Median survival in terminally ill cancer patients after enrollment was 38.5 days. Plasma concentrations of total, free, and acyl-LC in terminally ill cancer patients were 59.5±16.0, 46.1±14.2, and 13.4±5.9 µmol/L, respectively. These values were not significantly different from those in chemo-naive patients (58.3±18.1, 48.7±16.3, and 9.6±3.3 µmol/L, respectively). In addition, plasma LC levels in terminally ill patients showed no correlations with albumin or CRP values nor with other clinical parameters, such as fatigue or body weight loss. CONCLUSIONS: The present study suggested that plasma LC levels remain normal and its deficiency is not always common even in terminally ill and hospitalized palliative cancer patients.
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Carnitina/sangue , Hospitalização , Neoplasias/sangue , Doente Terminal , Estudos de Casos e Controles , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Cuidados Paliativos , Prognóstico , Estudos ProspectivosRESUMO
Recent advances in positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) have facilitated not only the diagnosis and staging of lung cancer, but also the prediction of treatment outcome. The present study was designed to assess the usefulness of early FDG-PET examination for predicting subsequent tumor size reduction in response to molecular targeted agents in metastatic non-small cell lung cancer (NSCLC) with sensitive gene anomalies. I. In 29 targeted lesions of 10 NSCLC patients, changes in FDG uptake before and on day 7 after the initiation of molecular targeted therapy (gefitinib, n = 7; crizotinib, n = 3) were compared with subsequent radiographic tumor size reduction by RECIST. FDG uptake was evaluated as the maximum standardized uptake value (SUVmax) of each targeted lesion. SUVmax decreased in all lesions after therapy (mean SUVmax 8.3 ± 3.4 before to 3.7 ± 1.8 after therapy, p < 0.05). The % decrease in SUVmax of each lesion was significantly correlated with the % tumor size reduction (r = 0.44). In addition, the reduction rate of SUVmax in metastatic bone lesions after initiation of molecular targeted therapy was significantly lower than that in targeted organs (27.1 ± 27.5 vs. 51.2 ± 21.3%, respectively, p < 0.05). Early reduction in FDG-PET uptake after initiation of molecular targeted agents was able to predict subsequent tumor reduction in patients harboring EGFR-mutated or ALK-positive NSCLC. In addition, nontargeted bone metastasis may have different glucose metabolism after TKI treatment compared with other involved organs.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe , Receptores ErbB/genética , Feminino , Fluordesoxiglucose F18/farmacocinética , Gefitinibe , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridinas/efeitos adversos , Piridinas/uso terapêutico , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Several studies have indicated that cisplatin (cis-diamminedichloroplatinum II; CDDP) causes urinary excretion of L-carnitine (LC). However, the underlying cofactors affecting the increased urinary excretion remain unclear. The present study was performed to evaluate the dynamics of LC in plasma and urine after CDDP chemotherapy and to examine the relations with clinical parameters, such as gender, body mass index (BMI), and renal function. METHODS: Twenty-two patients treated with CDDP therapy were selected. Blood and urine samples were taken from patients before starting CDDP treatment (day 0), on the next day (day 1), and on the seventh day (day 7). We measured plasma and urine concentrations of total, free, and acyl-LC, and examined the relationships with gender, age, treatment cycle, skeletal muscle mass, BMI, glomerular filtration rate, and change in creatinine concentration after CDDP administration. RESULTS: Both urinary and plasma concentrations of 3 types of LC increased markedly on day 1 and subsequently reverted to the pre-CDDP level on day 7. There was a positive correlation between the % changes in plasma and urine LC (correlation coefficient 0.59, p = 0.003) on day 1, but no significant relations were seen in other clinical parameters. CONCLUSIONS: CDDP transiently increased plasma LC levels. The mechanism seemed to involve recruitment for marked urinary loss of LC. However, these changes in plasma and urinary LC levels were not related to clinical factors, suggesting that the dynamics of LC were independent of preexisting physical parameters.
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Antineoplásicos/uso terapêutico , Carnitina/análise , Neoplasias/tratamento farmacológico , Índice de Massa Corporal , Carnitina/análogos & derivados , Carnitina/sangue , Carnitina/urina , Cisplatino/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologiaRESUMO
Hypercalcemia resulting in the elevation of serum parathyroid hormone-related protein (PTHrP) and suppression of serum PTH was observed in a patient with advanced cholangiocarcinoma (CCC) and multiple lymph node metastases. We confirmed humoral hypercalcemia of malignancy based on PTHrP-producing CCC. Chemotherapy with gemcitabine and cisplatin could not control the patient's serum PTHrP levels and the patient was affected with bisphosphonate-refractory hypercalcemia. We administered a single dose of denosumab, an anti-receptor activator of nuclear factor-kappaB ligand monoclonal antibody, and the patient's serum calcium levels remained close to the normal range for approximately 3 weeks without additional treatment.
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Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Hipercalcemia/sangue , Hipercalcemia/tratamento farmacológico , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/tratamento farmacológico , Neoplasias dos Ductos Biliares/complicações , Cálcio/sangue , Colangiocarcinoma/complicações , Humanos , Hipercalcemia/etiologia , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/etiologia , Proteína Relacionada ao Hormônio Paratireóideo/sangue , ProteínasRESUMO
BACKGROUND: Afatinib has been available in Japan for the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) since May 2014. We conducted an observational study in patients treated with afatinib in Nagano prefecture, focusing on response and associated toxicities. METHODS: We analyzed the clinical records of NSCLC patients treated with afatinib between May 2014 and February 2015. RESULTS: The records of a total of 73 patients (27 men, 46 women) with a median age of 69 years (range: 42-85 years) were analyzed. Afatinib was administered to 11 patients as a first-line therapy, but it was predominantly administered as a fifth-line or beyond therapy (32 cases, 43.8%). The overall response rates for afatinib as a first-line therapy and beyond second-line therapy were 80% (95% confidence interval [CI]: 55.2-100.0%) and 27.1% (95% CI: 14.5-39.7%), respectively. The main toxicities grade >3 included diarrhea (8.2%), skin rash (6.8%), nausea (6.8%), and appetite loss (6.8%). A low body surface area (BSA) (<1.5m2) was significantly associated with a higher frequency of diarrhea grade >2, compared with a higher BSA (≥â 1.5m2). Forty-eight patients (63.0%) were treated without a dose reduction of afatinib. CONCLUSIONS: Although the survival benefit with afatinib remains unclear, our observational analysis demonstrated the feasibility of using afatinib for EGFR-mutated NSCLC in clinical practice. In particular, a relatively high level of drug delivery is possible. In addition, a lower BSA may be a predictor of diarrhea in patients treated with afatinib.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Adulto , Afatinib , Idoso , Idoso de 80 Anos ou mais , Superfície Corporal , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Diarreia/induzido quimicamente , Receptores ErbB/genética , Estudos de Viabilidade , Feminino , Regulação da Expressão Gênica , Humanos , Japão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/efeitos adversos , Estudos RetrospectivosRESUMO
We herein encountered a case of abdominal wall dermatofibrosarcoma protuberans (DFSP) that developed pulmonary and pancreatic metastases 5 years after complete resection. Because specific rearrangements of the platelet-derived growth factor beta (PDGFB) locus by a novel fluorescence in situ hybridization method was detected, the patient was treated with imatinib mesylate at 400 mg/day. A partial response was achieved by imatinib without any specific toxicity. Although metastatic DFSP is an extremely rare disease, an evaluation of PDGFB fusion is essential and imatinib mesylate should be considered as an optimal therapeutic choice in patients with metastatic or locally advanced DFSP.
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Antineoplásicos/uso terapêutico , Dermatofibrossarcoma/patologia , Mesilato de Imatinib/uso terapêutico , Neoplasias Pulmonares/secundário , Neoplasias Pancreáticas/secundário , Neoplasias Cutâneas/patologia , Abdome , Dermatofibrossarcoma/cirurgia , Humanos , Hibridização in Situ Fluorescente , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Fator de Crescimento Derivado de PlaquetasRESUMO
Alectinib, a novel alternative anaplastic lymphoma kinase (ALK) inhibitor, is highly effective against ALK-positive non-small cell lung cancer (NSCLC) and is well tolerated. Molecular targeted agents generally have little contribution to alopecia. We encountered a case of alopecia that developed gradually over 2 months after initiation of alectinib administration for the treatment of ALK-positive NSCLC. The patient had no history of alopecia in previous treatments of cisplatin + pemetrexed and crizotinib. The present case indicates that alopecia should be taken into consideration as toxicity during alectinib treatment, which could adversely affect the psychological and emotional condition and quality of life even in patients treated with specific molecular targeted agents.
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BACKGROUND: S-1 is an oral anticancer drug, containing tegafur (a prodrug of 5-fluorouracil, 5-FU), 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. As renal dysfunction is known to increase exposure of 5-FU following S-1 administration, the incidence of severe adverse reactions is increased in patients with impaired renal function. However, no reliable information on its dose modification for patients with renal dysfunction has been provided. METHODS: We conducted a prospective pharmacokinetic study to develop an S-1 dosage formula based on renal function. Sixteen cancer patients with various degrees of renal function received a single dose of S-1 at 40 mg/m(2). A series of blood samples were collected at predefined times within 24 h to assess the plasma concentration profiles of 5-FU, 5-chloro-2,4-dihydroxypyridine, and tegafur. A mathematical model for the relationship between renal function and exposure of 5-FU was constructed by a population pharmacokinetic analysis. RESULTS: The clearance of 5-FU following S-1 administration was related to body surface area and creatinine clearance in the range 15.9-108.8 mL/min as estimated by the Cockcroft-Gault equation. The S-1 dosage formula was derived as follows:[Formula: see text]where AUC is the area under the concentration-time curve, CLcr is creatinine clearance, and BSA is body surface area. The recommended daily doses of S-1 in Asia and Europe were also proposed as nomograms according to exposure matching to the previously reported area under the concentration-time curve of 5-FU, which confirmed the efficacy and toxicity in pivotal registration studies. CONCLUSIONS: We have developed a novel formula for determining the S-1 dosage on the basis of renal function. Further validation is needed to confirm the formula for practical application.