Sunitinib rechallenge in advanced renal cell carcinoma: outcomes of a multicenter retrospective study.

PURPOSE: The aim of this multicenter study was to evaluate the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) who received sunitinib retreatment. METHODS: Clinical data from patients treated with sunitinib rechallenge in nine Spanish centers were retrospectively analyzed. All patients received first-line sunitinib until progression or intolerance, followed by one or more successive drugs and rechallenge with sunitinib thereafter. RESULTS: Thirty-seven patients were included. At first-line treatment, objective response rate (ORR) was 69.4% and median progression-free survival (PFS) was 19.4 months. At rechallenge, ORR was 27.2% and 39.4% of patients obtained stabilization of disease. Median PFS was 6.2 months. Clinical benefit was obtained by 21 patients (75%) with > 6-month interval between sunitinib treatments and by 1 patient (20%) among those with ≤ 6-month interval (P = 0.016). Hemoglobin levels ≥ lower level of normal were associated with clinical benefit (P = 0.019) and with PFS (P = 0.004). Median overall survival from start of first-line sunitinib was 52.7 months. No new adverse events were observed at rechallenge. CONCLUSIONS: Sunitinib rechallenge is a feasible treatment option for selected patients with mRCC.

Heart failure as first sign of development of cardiac metastases in a patient with diagnosis of papillary thyroid carcinoma on treatment with tyrosine-kinase inhibitors: differential diagnoses and clinical management.

BACKGROUND: Cardiac metastases from papillary thyroid carcinoma are very uncommon. Their incidence is rising due to improvements in survival and diagnosis; nevertheless, our patient is the fourth case reported up to date. There are no clinical trials available in this scenario. Therefore, treatment choice is made based on clinical experience and case reports; notably, the largest case report series was prior to the approval for using tyrosine-kinase inhibitors in thyroid cancer. PATIENT: A 73-year-old lady had dedifferentiated papillary thyroid cancer with ongoing sorafenib. After 9 months on this treatment, she presented with dyspnea and heart failure. Differential diagnosis included infection, progression of disease and cardiotoxicity. After a comprehensive assessment (echocardiography, computed tomography, PET, magnetic resonance), we found progression of lung disease, and the appearance of heart metastases. RESULTS: After recovering from the basal status, she started on second-line treatment with sunitinib, which was well-tolerated. She achieved stable disease with a decrease in tumor marker levels. CONCLUSIONS: We should include cardiac metastases in the differential diagnosis of heart failure in cancer patients. Magnetic resonance imaging is the gold standard for assessment. Sorafenib is the mainstay of the first-line therapy in metastatic thyroid cancer, achieving long-term disease control with good tolerance. Sunitinib could be a safe second-line treatment option (not cardiotoxicity related) with promising results. Therefore, our report presents a sequence of treatment with tyrosine-kinase inhibitors in metastatic thyroid carcinoma with an encouraging outcome, which deserves further investigation.

Pleuropulmonary angiosarcoma involving the liver, the jejunum and the spine, developed from chronic tuberculosis pyothorax: Multidisciplinary approach and review of literature.

Pleuropulmonary angiosarcomas are very rare, with less than fifty cases reported in the literature. In most cases, the etiology is unknown but the presence of a chronic tuberculous pyothorax has been reported in several Asian case reports as a possible risk factor. We report the case of a Caucasian 68-year old man who presented with a pleuropulmonary angiosarcoma that arose from a chronic tuberculous pyothorax and which involved the ribs and the vertebrae, the psoas muscle, and the jejunum. The patient received adapted anti-tuberculosis treatment, embolization of the mass in the small bowel, palliative external beam radiotherapy on the spine and systemic chemotherapy with liposomal non-pegylated doxorubicin and ifosfamide. With this multidisciplinary approach the patient's symptoms were well controlled and he achieved a complete metabolic response after six cycles of chemotherapy. Unfortunately, the patient died after eight months from the beginning of chemotherapy due to an acute lung injury secondary to extensive bilateral interstitial infiltrates. Opportunistic pathogens or drug-induced lung toxicity were the most probable causes. Treatment with liposomal non-pegylated doxorubicin and ifosfamide could be a reasonable option in pleuropulmonary angiosarcoma but it should be validated in clinical trials. Chronic pyothorax seems to be a predisposing factor for the development of pleural angiosarcoma but further investigations are required to assess a causal association.

Vitamin D insufficiency and subclinical atherosclerosis in non-diabetic males living with HIV.

INTRODUCTION: Vitamin D insufficiency (VDI) has been associated with increased cardiovascular risk in the non-HIV population. This study evaluates the relationship among serum 25-hydroxyvitamin D [25(OH)D] levels, cardiovascular risk factors, adipokines, antiviral therapy (ART) and subclinical atherosclerosis in HIV-infected males. METHODS: A cross-sectional study in ambulatory care was made in non-diabetic patients living with HIV. VDI was defined as 25(OH)D serum levels <75 nmol/L. Fasting lipids, glucose, inflammatory markers (tumour necrosis factor-α, interleukin-6, high-sensitivity C-reactive protein) and endothelial markers (plasminogen activator inhibitor-1, or PAI-I) were measured. The common carotid artery intima-media thickness (C-IMT) was determined. A multivariate logistic regression analysis was made to identify factors associated with the presence of VDI, while multivariate linear regression analysis was used to identify factors associated with common C-IMT. RESULTS: Eighty-nine patients were included (age 42 ± 8 years), 18.9% were in CDC (US Centers for Disease Control and Prevention) stage C and 75 were on ART. VDI was associated with ART exposure, sedentary lifestyle, higher triglycerides levels and PAI-I. In univariate analysis, VDI was associated with greater common C-IMT. The multivariate linear regression model, adjusted by confounding factors, revealed an independent association between common C-IMT and patient age, time of exposure to protease inhibitors (PIs) and impaired fasting glucose (IFG). In contrast, there were no independent associations between common C-IMT and VDI or inflammatory and endothelial markers. CONCLUSIONS: VDI was not independently associated with subclinical atherosclerosis in non-diabetic males living with HIV. Older age, a longer exposure to PIs, and IFG were independent factors associated with common C-IMT in this population.

The determination of total testosterone and free testosterone (RIA) are not applicable to the evaluation of gonadal function in HIV-infected males.

INTRODUCTION: Hypogonadism is common in human immunodeficiency virus (HIV)-infected men; the high concentration of sex hormone binding globulin (SHBG) in this population, induces a "false increase" in total testosterone (TT) values. AIMS: To validate the determination of TT and measured free testosterone (FT [radioimmunoassay {RIA}]) for hypogonadism diagnosis in an HIV-infected population using calculated free testosterone (CFT) as reference method; and also to determine the prevalence and identify the risks factors of hypogonadism. METHODS: Cross-sectional, observational study. Ninety HIV-infected males (42 ± 8.2 years), not HCV coinfected, antiretroviral therapy (ART)-naive (14 patients), on current ART with enhanced protease inhibitor (PI) (39 patients), or patients on PI-naive ART (NN) (37 patients). MAIN OUTCOME MEASURES: CFT was calculated by determining TT, SHBG, and albumin (Vermeulen's formula); hypogonadism was defined as CFT <0.22 nmol/L (reference range for young healthy males in our laboratory); sensitivity of TT and FT (RIA) for hypogonadism diagnosis was calculated. RESULTS: Twelve patients (13.3%, 95% confidence interval [CI] 7.8-21.9) by CFT presented hypogonadism. TT and FT (RIA) presented a sensitivity of less than 30% in the diagnosis of hypogonadism. Logistic regression multivariate analysis confirmed an independent association between hypogonadism, the patient's age per decade, odds ratio (OR) 6.9 (CI 1.9-24.8; P = 0.003), and longer duration of HIV infection per decade, OR 13.1 (CI 1.3-130.6; P = 0.02). Hypogonadism was associated with erectile dysfunction. CONCLUSIONS: TT and FT (RIA) are not useful in the differential diagnosis of hypogonadism in HIV-infected males. There is a significant prevalence of hypogonadism in HIV-infected males, with the patient's age and duration of the disease being the only identifiable risk factors.

Risk factors for sexual and erectile dysfunction in HIV-infected men: the role of protease inhibitors.

OBJECTIVES: To determine the prevalence of erectile dysfunction in a cohort of HIV-infected men in a stable clinical state, the effect of exposure to antiretroviral therapy on sexual dysfunction and to identify the risk factors. DESIGN: This is a cross-sectional, observational study. METHODS: HIV-infected men without hepatitis C virus coinfection were included if they were antiretroviral therapy-naive (naive group), on current treatment with an enhanced protease inhibitor (protease inhibitor group) or on current treatment with two to three nucleoside reverse transcriptase inhibitors along with one nonnucleoside reverse transcriptase inhibitor and never having received treatment with protease inhibitor (nonnucleoside reverse transcriptase inhibitor group). Erectile dysfunction was defined as an ejection fraction of 25 or less (International Index of Erectile Function-15). RESULTS: Ninety patients were included, with an age of 42 +/- 8.2 years and CD4 cell count of 465 cells/microl [P25-75 361-676]: 18.9% in Centers for Disease Control and Prevention class C and 72.2% with undetectable viral load. Seventy-six patients (84.4%) were receiving antiretroviral therapy, 39 (43.3%) in the protease inhibitor group. The prevalence of lipodystrophy was 31.5%. Forty-seven (53.4%) patients had an erectile dysfunction. Multivariate logistic regression analysis confirmed that there was an independent association between the patients' age (per decade; odds ratio 2.2, 95% confidence interval 1.04-4.5, P = 0.04) and greater duration of exposure to protease inhibitor (per year; odds ratio 1.6, 95% confidence interval 1.12-2.4, P = 0.01). Older age, depression and lipodystrophy, combined with the duration of exposure to protease inhibitor, determined a lower score on various sexual dysfunction domains (P < 0.05). CONCLUSION: There is a high prevalence of erectile dysfunction in HIV-infected men, with age and the duration of exposure to protease inhibitor being the only identifiable risk factors.