Seguimiento de 20 pacientes portadores de fibrosis pulmonar idiopática tratados con nintedanib / Follow-up of 20 patients with idiopathic pulmonary fibrosis treated with nintedanib

Se presenta un estudio observacional compasivo de seguimiento de 20 pacientes portadores de Fibrosis Pulmonar Idiopática tratados con Nintedanib, que muestra que Nintedanib es un medicamento en general bien tolerado, sin efectos adversos serios, que otorga una sobrevida más prolongada que la que cabría esperar en pacientes con esta enfermedad.

A compassionate observational follow-up study of 20 patients with Idiopathic Pulmonary Fibrosis treated with Nintedanib is presented, showing that Nintedanib is a generally well-tolerated drug, with no serious adverse effects, that grants a longer survival in real-life patients.

Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Sunitinib treatment in patients with advanced renal cell cancer: the Brazilian National Cancer Institute (INCA) experience

ABSTRACT Purpose: The aim of this study was to assess the impact of sunitinib treatment in a non-screened group of patients with metastatic renal cell cancer (mRCC) treated by the Brazilian Unified Health System (SUS) at a single reference institution. Material and Methods: Retrospective cohort study, which evaluated patients with mRCC who received sunitinib between May 2010 and December 2013. Results: Fifty-eight patients were eligible. Most patients were male 41 (71%), with a median age of 58 years. Nephrectomy was performed in 41 (71%) patients with a median interval of 16 months between the surgery and initiation of sunitinib. The most prevalent histological subtype was clear cell carcinoma, present in 52 (91.2%) patients. In 50 patients (86%), sunitinib was the first line of systemic treatment. The main adverse effects were fatigue (57%), hypothyroidism (43%), mucositis (33%) and diarrhea (29%). Grade 3 and 4 adverse effects were infrequent: fatigue (12%), hypertension (12%), thrombocytopenia (7%), neutropenia (5%) and hand-foot syndrome (5%). Forty percent of patients achieved a partial response and 35% stable disease, with a disease control rate of 75%. Median progression free survival was 7.6 months and median overall survival was 14.1 months. Conclusion: Sunitinib treatment was active in the majority of patients, especially those with low and intermediate risk by MSKCC score, with manageable toxicity. Survival rates were inferior in this non-screened population with mRCC treated in the SUS.

Vemurafenib and cutaneous adverse events - report of five cases

Vemurafenib is a selective inhibitor of V600E-mutant BRAF protein used to treat metastatic and unresectable melanoma. Clinical trials have shown increased overall survival and progression-free survival in patients treated with Vemurafenib. However, cutaneous adverse events are common during treatment. We report fi ve cases of metastatic melanoma with BRAF V600E positivity, treated with Vemurafenib and its cutaneous adverse events. Dermatologists and oncologists need to be aware of possible skin changes caused by this medication, which is increasingly employed in melanoma treatment. Monitoring of patients during therapy is important for early treatment of adverse cutaneous cutaneous adverse events, improvement in quality of life and adherence to treatment.

Aortic dissection during antiangiogenic therapy with sunitinib. A case report / Dissecção de aorta em terapia anti-angiogênica com sunitinibe. Um relato de caso

CONTEXT: Sunitinib is an antiangiogenic drug that has been approved for treating metastatic renal cancer. Its action as a tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFRs) and other angiogenesis receptors may lead to adverse effects such as hypertension and heart failure. However, reports in the literature on an association between sunitinib therapy and acute aortic dissection are rare. CASE REPORT: We report the case of a 68-year-old man with metastatic renal carcinoma who developed acute aortic dissection during sunitinib therapy. He had no history of hypertension or any other risk factor for aortic dissection. After aortic dissection had been diagnosed, sunitinib was withdrawn and an aortic endoprosthesis was placed. Afterwards, the patient was treated clinically with antihypertensive drugs and new therapy for renal cancer consisting of temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR) pathway. CONCLUSION: Hypertension is a common event when antiangiogenic drugs are used in oncology. However, knowledge of other severe cardiovascular events that may occur in these patients, such as acute aortic dissection, is important. Adequate control over arterial pressure and frequent monitoring of patients during the first days of antiangiogenic therapy is essential for early diagnosis of possible adverse events. .

CONTEXTO: Sunitinibe é uma droga antiangiogênica aprovada para tratamento de câncer renal metastático. Sua ação como inibidor de tirosina quinase de receptores de fatores de crescimento do endotélio vascular (VEGFR) e de outros receptores de angiogênese pode levar a eventos adversos como hipertensão e insuficiência cardíaca. No entanto, é escassa na literatura a associação da terapia com sunitinibe e dissecção aguda de aorta. RELATO DE CASO: Relatamos o caso de um paciente do sexo masculino de 68 anos com câncer renal metastático que desenvolveu dissecção aguda de aorta durante tratamento com sunitinibe. O paciente não tinha histórico prévio de hipertensão nem outro fator de risco para dissecção de aorta. Após diagnóstico da dissecção de aorta, a droga foi suspensa e o paciente foi submetido à colocação de endoprótese na aorta, evoluindo posteriormente com controle clínico da pressão arterial e nova terapia para câncer renal com tensirolimo, um inibidor da via proteína alvo da rapamicina em mamíferos (mTOR). CONCLUSÕES: A hipertensão é um evento comum com uso de drogas antiangiogênicas na oncologia. No entanto, é importante o conhecimento de outros eventos cardiovasculares graves, como dissecção aguda de aorta, que podem ocorrer nesses pacientes. Controle adequado da pressão arterial e monitorização frequente dos pacientes nos primeiros dias de terapia antiangiogênica são essenciais para diagnóstico precoce de possíveis eventos graves. .

Onicólisis exudativa y paroniquia bacteriana aguda en relación con BIBF-1120 y paclitaxel: respuesta a la terapia tópica / Exudative onycholysis and acute bacterial paronychia related to BIBF-1120 and paclitaxel: response to topical therapy

Se presenta el caso de una paciente de 50 años de edad con cáncer de mama tratada con paclitaxel y BIBF 1120 semanal. La paciente desarrolló al final del duodécimo ciclo de quimioterapia una onicólisis distal, con exudado seroso intenso en el hiponiquio, dolor y mal olor en todas las uñas de las manos. Se trató con ácido fusídico tópico y aceponato de metilprednisolona al 1% dos veces al día, con una excelente respuesta desde los tres primeros días de tratamiento. A la semana de iniciar la terapia tópica, se observó una paroniquia bacteriana con la pérdida de la uña del quinto dedo de la mano izquierda, con cultivos positivos para Staphylococcus aureus sensible a meticilina. Hay pocos casos publicados de onicólisis exudativa asociada a quimioterapia. Sin embargo, están especialmente relacionados con paclitaxel. No se observaron recurrencias de las alteraciones ungueales semanas después de culminar la quimioterapia. Los corticoides tópicos y el ácido fusídico podrían ser considerados como una opción terapéutica cuando la onicólisis exudativa relacionada con paclitaxel esté establecida.

A case of a 50 years-old breast cancer patient treated with weekly paclitaxel and BIBF 1120 is reported herein. At the end of the twelfth cycle of chemotherapy, the patient developed distal onycholysis with intense hyponychium serous exudates, pain and malodor in all her fingernails. It was treated with topical fusidic acid and 1% methylprednisolone aceponate two times daily, with an excellent clinical response from the first three days of treatment. Bacterial paronychia with nail plate loss of the fifth left fingernail was observed a week after the topical therapy was started, with positive cultures for Methicillin susceptible Staphylococcus aureus. There are few reported cases of exudative onycholysis associated with chemotherapy. However, these are especially related to paclitaxel. No recurrences of nail disturbances were observed weeks after the end of chemotherapy. Topical corticosteroids and fusidic acid could be considered as a therapeutic option when exudative onycholysis related to paclitaxel is established.

Risks associated with sunitinib use and monitoring to improve patient outcomes

No abstract available.

Renal adverse effects of sunitinib and its clinical significance: a single-center experience in Korea

BACKGROUND/AIMS: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. METHODS: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. RESULTS: One hundred and fifty-five patients (mean age, 58.7 +/- 12.6 years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. CONCLUSIONS: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.

A Case of Pneumatosis Intestinalis Associated with Sunitinib Treatment for Renal Cell Carcinoma / 대한소화기학회지

Sunitinib as a multitarget tyrosine kinase inhibitor is one of the anti-tumor agents, approved by the United States Food and Drug Administration to use treat gastrointestinal stromal tumor and metastatic renal cell carcinoma. The agent is known to commonly induce adverse reactions such as fatigue, nausea, diarrhea, stomatitis, esophagitis, hypertension, skin toxicity, reduciton in cardiac output of left ventricle, and hypothyroidism. However, it has been reported to rarely induce adverse reactions such as nephrotic syndrome and irreversible reduction in renal functions, and cases of intestinal perforation or pneumatosis interstinalis as such reactions have been consistently reported. In this report, a 66-year old man showing abdominal pain had renal cell carcinoma and history of sunitinib at a dosage of 50 mg/day on a 4-weeks-on, 2-weeks-off schedule. Seven days after the third cycle he was referred to the hospital because of abdominal pain. Computed tomography showed pneumoperitoneum with linear pneumatosis intestinalis in his small bowel. The patient underwent surgical exploration that confirmed the pneumatosis intestinalis at 100 cm distal to Treitz's ligament. We report a rare case of intestinal perforation with pneumatosis intestinalis after administration of sunitinib to a patient with metastatic renal cell carcinoma.

Síndrome de lisis tumoral en un paciente con cáncer de riñón tratado con sunitinib / Tumor lysis syndrome in a patient with a renal carcinoma treated with sunitinib

El síndrome de lisis tumoral (SLT) es un trastorno metabólico que ocurre como consecuencia de una destrucción celular masiva. Se caracteriza por la presencia de hiperuricemia, hiperfosfatemia, hipocalcemia e hiperkalemia, y predispone al desarrollo de insuficiencia renal aguda. En la mayoría de los casos el SLT ocurre luego de instaurarse un tratamiento antitumoral y es más frecuente en tumores de alto grado de malignidad y alta sensibilidad a la quimioterapia. Presentamos el caso de un paciente con diagnóstico de cáncer de riñón recidivado que presenta un SLT e insuficiencia renal aguda luego de iniciar tratamiento con sunitinib.

The tumor mor lysis syndrome (TLS) is a metabolic disorder resulting from a massive tumor breakdown. It is characterized by hyperuricemia, hyperphosphatemia, hypocalcemia and hyperkalemia and predisposes to acute renal failure. TLS usually occurs after the initiation of cytotoxic therapy and is more frequent in the case of neoplasias with a high proliferative rate or that are highly chemo-sensitive. We report the case of a man with a recurrent kidney cancer who presented with a TLS and acute renal failure after initiation of sunitinib.

Efficacy and tolerability of trandolapril in mild to moderate hypertension--a double blind comparative clinical trial with enalapril in Indian population.

Several large scale clinical trials have demonstrated that angiotensin converting enzyme inhibitors offer cardiovascular and renal protection independent of their effects on systolic BP. Trandolapril is a new angiotensin converting enzyme inhibitor approved for the treatment of hypertension. The potential advantages of this drug are long duration of action and better tolerability. The objective of the study was to compare the efficacy and tolerability of trandolapril with that of enalapril in mild to moderate hypertension in Indian population. In this double blind, multicentric, parallel comparative clinical study, 120 patients with mild to moderate hypertension were randomly assigned to receive trandolapril 2 mg or enalapril 5 mg once daily for 8 weeks. The attainment of sitting diastolic blood pressure <90 mmHg at the end of 8th week was considered as primary outcome measure and attainment of diastolic blood pressure <90 mmHg or reduction of at least 10 mmHg diastolic blood pressure compared to baseline at any visit was considered as secondary outcome measures. 98.4% patients treated with trandolapril and 92.6% patients treated with enalapril fulfilled the primary outcome measure. 54, 72 and 62% patients on trandolapril and 52, 61 & 64% patients on enalapril fulfilled secondary outcome measure at the end of 2nd, 4th and 8th week respectively. Also trandolapril was better tolerated than enalapril with no significant abnormality in lab parameters.

Security and maximal tolerated doses of fluvastatin in pediatric cancer patients

Background. The role of cholesterol in neoplasic cell growth and its inhibition by drugs has recently been studied. Cholesterol biosynthesis inhibitors have been used as adjuvants in the treatment of cancer and possibly as prophylactic in carcinogenesis. objetive. The objetive of the study was to determine the maximal tolerated doses (MTD) and toxic effects of fluvastatin in pediatric cancer patients. Methods. This study was carried out in a thirid level Social Security Hospital in Mexico City. We included pediatric patients from april 1996 to May 1997. All were terminal cancer patients who did not respond to conventional therapies. Fluvastatin was give p.o. at doses of 2 mg/kg/day dor 14 days every 4 weeks in three patients. Subsequent cohorts of three patients each had increments of 2 mg/kg/day of the drug until maximal tolerated doses were found. Toxic effects of the drug were evaluated by physical exploration, laboratory assays and a questionnaire given to each patient. Results. Twelve patients were included. Diagnoses included two osteosarcomas, eight central nervous system tumors, one lung tumor, and one Ewing's sarcoma. Ten patients died within 1 to 18 months. Two are aolive 22 months after inclusion into the study, both with anaplasic astrocytoma. A total of 27 courses wer administered. The MTD was 8 mg/kg/day. Toxic effects were insomnia, nausea, vomiting, abdominal distention and myalgias. Txocicity was dose-dependent. Laboratory assays demonstrated no significant changes during treatment. Conclusions. Fluvastatin can be safely used at doses of 8 mg/kg/day in pediatric patients with cancer. This dose should be used in additional trials