The relationship between abdominal fat and change in left ventricular ejection fraction in cancer patients.

OBJECTIVES: Prior studies have identified a relationship between body mass index (BMI) and intraperitoneal (IP) fat with heart failure; however, in prior studies of cancer patients receiving potentially cardiotoxic chemotherapy, elevations in BMI have not necessarily been associated with decrements in heart function. This study tested the hypothesis that IP fat may be associated with left ventricular ejection fraction (LVEF) decline among cancer patients receiving potentially cardiotoxic chemotherapy. METHODS: In this prospective study of 61 cancer patients (23 breast cancer, 32 lymphoma, and 6 sarcoma), IP fat and other assessments of body composition, and changes in LVEF from pre- to postcancer treatment using noninvasive magnetic resonance imaging was ascertained. RESULTS: After accounting for age, baseline LVEF, and confounding variables, pre- to 24-month post-treatment LVEF changes were inversely correlated with IP fat (r = -0.33; p = 0.02) and positively correlated with measures of subcutaneous (SQ) fat (r = 0.33; p = 0.01). These LVEF changes were not correlated with BMI (r = 0.12; p = 0.37). CONCLUSION: Among patients receiving potentially cardiotoxic chemotherapy, pretreatment IP fat was associated with subsequent declines in LVEF. There was no association between BMI and LVEF decline. These findings may be related to a potential protective effect of SQ fat.

Cardiovascular Assessment Tool for Breast Cancer Survivors and Oncology Providers: Usability Study.

BACKGROUND: Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors' attainment or maintenance of cardiovascular health. OBJECTIVE: We sought to evaluate survivors' awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers. METHODS: Breast cancer survivors (n=49) recruited from a survivorship clinic interacted with the cardiovascular health tool and completed pre and posttool assessments about cardiovascular health knowledge and perceptions of the tool. Oncologists, physician assistants, and nurse practitioners (n=20) who provide care to survivors also viewed the cardiovascular health tool and completed assessments of perceived usability and acceptability. RESULTS: Enrolled breast cancer survivors (84% White race, 4% Hispanic ethnicity) had been diagnosed 10.8 years ago (SD 6.0) with American Joint Committee on Cancer stage 0, I, or II (45/49, 92%). Prior to viewing the tool, 65% of survivors (32/49) reported not knowing their level for one or more cardiovascular health factors (range 0-4). On average, only 45% (range 0%-86%) of survivors' known cardiovascular health factors were at an ideal level. More than 50% of survivors had ideal smoking status (45/48, 94%) or blood glucose level (29/45, 64%); meanwhile, less than 50% had ideal blood pressure (12/49, 24%), body mass index (12/49, 24%), cholesterol level (17/35, 49%), diet (7/49, 14%), and physical activity (10/49. 20%). More than 90% of survivors thought the tool was easy to understand (46/47, 98%), improved their understanding (43/47, 91%), and was helpful (45/47, 96%); overall, 94% (44/47 survivors) liked the tool. A majority of survivors (44/47, 94%) thought oncologists should discuss cardiovascular health during survivorship care. Most (12/20, 60%) oncology providers (female: 12/20, 60%; physicians: 14/20, 70%) had been practicing for more than 5 years. Most providers agreed the tool provided useful information (18/20, 90%), would help their effectiveness (18/20, 90%), was easy to use (20/20, 100%), and presented information in a useful format (19/20, 95%); and 85% of providers (17/20) reported they would use the tool most or all of the time when providing survivorship care. CONCLUSIONS: These usability data demonstrate acceptability of a cardiovascular health clinical decision support tool in oncology practices. Oncology providers and breast cancer survivors would likely value the integration of such apps in survivorship care. By increasing awareness and communication regarding cardiovascular health, electronic health record-enabled tools may improve survivorship care delivery for breast cancer and ultimately patient outcomes.

Simultaneous Left Ventricular Volume and Strain Changes During Chemotherapy Associate With 2-Year Postchemotherapy Measures of Left Ventricular Ejection Fraction.

Background Although changes in left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume, and global circumferential strain occur during cancer treatment, the relationship of these changes to the 2-year post-cancer-treatment measures of left ventricular ejection fraction (LVEF) are unknown. Methods and Results In a prospective, continuously recruited cohort of 95 patients scheduled to receive potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or soft tissue sarcoma, measures of left ventricular end-diastolic volume, LVESV, global circumferential strain, and LVEF were acquired via cardiac magnetic resonance imaging before and then 3 and 24 months after initiating treatment by individuals blinded to all patient identifiers. Participants had an average age of 54±15 years; 68% were women, and 82% were of white race. LVEF declined from 62±7% to 58±9% over the 24 months (P<0.0001), with 42% of participants experiencing a >5% decline in LVEF at 24 months. Predictors of a 24-month >5% decline in LVEF included the following factors from baseline to 3 months into treatment: (1) >3-mL increases in LVESV (P=0.033), (2) >3-mL increases in LVESV or 10-mL declines in left ventricular end-diastolic volume with little change in LVESV (P=0.001), or (3) ≥10% deteriorations in global circumferential strain with little change in LVESV (P=0.036). Conclusion During receipt of potentially cardiotoxic chemotherapy, increases in LVESV, the absence of its deterioration during decreases of left ventricular end-diastolic volume, or the deterioration of global circumferential strain without a marked decrease in LVESV help identify those who will develop more permanent 2-year declines in LVEF.

Association between glycemic control, age, and outcomes among intensively treated patients with acute myeloid leukemia.

PURPOSE: To investigate the impact of hyperglycemia and glycemic variability during intensive acute myeloid leukemia therapy (AML) on outcomes by age. METHODS: Retrospective study of 262 consecutive patients with newly diagnosed AML hospitalized for intensive induction. Hyperglycemia was assessed by mean blood glucose (BG) (mg/dL) during hospitalization and glycemic variability was determined by the standard deviation (SD) of mean BG. Outcomes were complete remission ± incomplete count recovery (CR + CRi), and overall survival (OS). We used logistic regression to evaluate CR + CRi, and Cox proportional hazard models for OS, stratified by age (< 60 vs ≥ 60 years). RESULTS: Older patients (N = 138, median age 70) had higher baseline comorbidity (CCI > 1 60.1% vs 25.8%) and prevalence of diabetes (20.3% vs 7.3%) compared to younger (N = 124, median age 47). The mean ± SD number of BG values obtained per patient during hospitalization was 61 ± 71. The mean (± SD) glucose (mg/dL) during hospitalization was 121.7 (25.9) in older patients (≥ 60 years) versus 111.6 (16.4) in younger. In older patients, higher mean glucose and greater glycemic variability were associated with lower odds of remission (OR 0.80, 95% CI 0.69-0.93 and OR 0.73, 95% CI 0.61-0.88 respectively, per 10-unit increase) and higher mortality rates (HR 1.13, 95% CI 1.05-1.21 and HR 1.17, 95% CI 1.09-1.26, respectively, per 10-unit increase) in multivariate analyses. CONCLUSIONS: Our observations that hyperglycemia and increased glycemic variability were associated with lower remission rates and increased mortality in older patients suggest glycemic control may be a potentially modifiable factor to improve AML outcomes.

Evaluation of growth hormone response to GHRH plus arginine test in children with idiopathic short stature: role of peak time.

PURPOSE: To describe the course of growth hormone response to growth hormone releasing hormone (GHRH) plus arginine provocative test in children with idiopathic short stature (ISS) and to evaluate the role of peak time. METHODS: A retrospective study was performed analyzing 344 GHRH plus arginine provocative tests performed in children and adolescents with short stature. Serum GH levels were measured at four-time points (T0', T30', T45' and T60') and GH peak was defined as the maximum value at any time point. Mean (T30'-T60') GH value and area under the curve (AUC) were calculated. RESULTS: When analyzing the time of peak at the provocative test, the most frequent peak time was T45' (53.8%) in the ISS group, with no differences in gender, age, and pubertal stage. Analyzing GHD subjects, the most frequent time of peak was T30 (50%). Analyzing the whole population, the GH T0' levels were significantly lower in subjects with the GH peak at T45' than those with the GH peak at T30' (1.7 ± 2.0 vs. 3.2 ± 4.0, p < 0.001). In subjects with GH peak at T45', the value of GH peak, AUC and mean GH were significantly higher than in those with GH peak at T30' and T60'. A direct correlation was found between the value of GH peak and growth velocity SDS (r = 0.127, p = 0.04) and a negative one between GH peak and GH level at T0' (r = - 0.111, p = 0.04), even when adjusted for gender, age, pubertal stage and BMI Z score. CONCLUSIONS: The time peak at 45 min seems to be associated with a better response to the test considering GH peak, mean and AUC. Patients with a GH peak at 30 min more probably could have a derangement in GH secretion showing worst growth pattern and/or a GH deficiency and should be carefully observed.

Hyperglycemia during first-line R-CHOP or dose adjusted R-EPOCH chemotherapy for non-Hodgkin lymphoma is prevalent and associated with chemotherapy alteration - a retrospective study.

High-dose glucocorticoids such as prednisone are combined with cytotoxic chemotherapy in the R-CHOP or dose adjusted R-EPOCH regimens used for non-Hodgkin lymphoma (NHL). In this retrospective study, our primary objective was to evaluate the incidence of hyperglycemia during first-line R-CHOP or DA-EPOCH-R. The secondary objectives were to evaluate the incidence of chemotherapy alteration and overall survival in those with and without hyperglycemia. One hundred and sixty patients were eligible. We found that 47% of all patients had at least one hyperglycemic episode and hyperglycemia was associated with chemotherapy alteration (p = .028). Multivariate analysis revealed international prognostic index (IPI) ≥ 3 (p = .045) and chemotherapy alteration (p = .001) were associated with decreased overall survival. We conclude that hyperglycemia is common during first-line NHL treatment with R-CHOP or DA-EPOCH-R, even in the absence of known diabetes and is associated with alterations of chemotherapy. Baseline pre-PET scan fasting blood glucose of 100 mg/dL or higher may predict hyperglycemia during therapy.

A Phase II Clinical Trial of CPI-613 in Patients with Relapsed or Refractory Small Cell Lung Carcinoma.

BACKGROUND: Small cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80% but with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells. METHODS: We evaluated CPI-613 with a single-arm, open-label phase II study in patients with relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and 4 of weeks 1-3 of 4 week cycle. The primary outcome was response rate as assessed by CT imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and toxicity. Twelve patients were accrued (median age 57yo) who had previously received between 1 and 4 lines of chemotherapy (median 1) for SCLC with a treatment-free interval of less than 60 days in 9 of the 12 patients. RESULTS: No complete or partial responses were seen. Ten patients (83%) progressed as best response and 2 (17%) were not evaluable for response. Median time to progression was 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall survival of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack of efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequently treated with standard topotecan then demonstrated treatment response with survival for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synergy in-vitro for CPI-613 with topotecan. CONCLUSIONS: Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combination with a topoisomerase inhibitor is warranted.

Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (EPOCH) With or Without Rituximab as First-Line Therapy for Aggressive Non-Hodgkin Lymphoma.

INTRODUCTION: Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) was developed in an effort to overcome inadequate drug concentrations and compensate for increased drug clearance. The goal of the present study was to examine the risk factors and outcomes of patients with aggressive non-Hodgkin lymphoma (aNHL) treated with DA-EPOCH. PATIENTS AND METHODS: We report the data from 136 patients with previously untreated aNHL who received infusional DA-EPOCH chemotherapy with or without rituximab from 2005 to 2013. Overall survival was estimated using Kaplan-Meier methods. Univariate and multivariate logistic regression was used to determine the factors associated with death, progression, or relapse at 2 years. RESULTS: The overall response rate was 82%. The relapse-free survival rate at 1, 3, and 5 years was 68%, 63%, and 52% with 95% confidence intervals (CIs) of 0.59% to 0.85%, 0.54% to 0.70%, and 0.31% to 0.70%, respectively. Patients with T-cell aNHL had an increased risk of death, progression, or relapse (Odds Ratio, 3.5; 95% CI, 1.4-8.8) compared with those with B-cell aNHL. In multivariate analysis, current smoking, disease in the bone marrow, and the number of cycles completed were independent predictors of death and relapse. CONCLUSION: Our data suggest that EPOCH with or without rituximab is active in both B- and T-cell aNHL. Toxicity did not significantly affect timing of treatment delivery or treatment outcomes. Dose adjustment by hematopoietic nadir similarly had no effect. The effect of smoking during chemotherapy should be evaluated further.

Relation of Pre-anthracycline Serum Bilirubin Levels to Left Ventricular Ejection Fraction After Chemotherapy.

Myocardial injury because of oxidative stress manifesting through reductions in left ventricular ejection fraction (LVEF) may occur after the administration of anthracycline-based chemotherapy (A-bC). We hypothesized that bilirubin, an effective endogenous antioxidant, may attenuate the reduction in LVEF that sometimes occurs after receipt of A-bC. We identified 751 consecutively treated patients with cancer who underwent a pre-A-bC LVEF measurement, exhibited a serum total bilirubin level <2 mg/dl, and then received a post-A-bC LVEF assessment because of symptomatology associated with heart failure. Analysis of variance, Tukey's Studentized range test, and chi-square tests were used to evaluate an association between bilirubin and LVEF changes. The LVEF decreased by 10.7 ± 13.7%, 8.9 ± 11.8%, and 7.7 ± 11.5% in group 1 (bilirubin at baseline ≤0.5 mg/dl), group 2 (bilirubin 0.6 to 0.8 mg/dl), and group 3 (bilirubin 0.9 to 1.9 mg/dl), respectively. More group 1 patients experienced >15% decrease in LVEF compared with those in group 3 (p = 0.039). After adjusting for age, coronary artery disease/myocardial infarction, diabetes mellitus, hematocrit, and the use of cardioactive medications, higher precancer treatment bilirubin levels and lesser total anthracycline doses were associated with LVEF preservation (p = 0.047 and 0.011, respectively). In patients treated with anthracyclines who subsequently develop symptoms associated with heart failure, pre-anthracycline treatment serum bilirubin levels inversely correlate with subsequent deterioration in post-cancer treatment LVEF. In conclusion, these results suggest that increased levels of circulating serum total bilirubin, an intrinsic antioxidant, may facilitate preservation of LVEF in patients receiving A-bC for cancer.

Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study.

BACKGROUND: Cetuximab in combination with platinum and 5-fluorouracil is the standard of care in the first-line treatment of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Cetuximab and taxane combinations have shown promising activity. This study evaluated the efficacy and safety of four cycles of docetaxel associated with cisplatin and cetuximab (TPEx), followed by maintenance with cetuximab every 2 weeks. PATIENTS AND METHODS: Patients with a histologically confirmed HNSCC with metastasis or recurrence unsuitable for locoregional curative treatment received docetaxel and cisplatin (75 mg/m(2) both) at day 1 and weekly cetuximab 250 mg/m(2) (loading dose of 400 mg/m(2)), repeated every 21 days for four cycles, followed by maintenance cetuximab 500 mg/m(2) every 2 weeks until progression or unacceptable toxicity. Prophylactic administration of granulocyte colony-stimulating factor was done systematically after each chemotherapy cycle. Patients had a good general status (performance status ≤1) and were under 71 years. Prior total doses of cisplatin exceeding 300 mg/m(2) were not allowed. The primary end point was objective response rate (ORR) after four cycles. RESULTS: Fifty-four patients were enrolled. The primary end point was met with an ORR of 44.4% (95% CI 30.9-58.6). Median overall and progression-free survivals were, respectively, 14 months (95% CI 11.3-17.3) and 6.2 months (95% CI 5.4-7.2). The most common grade 3/4 adverse events were skin rash (16.6%) and non-febrile neutropenia (20.4%). There were one pulmonary embolism and two infectious events leading to death. CONCLUSIONS: The TPEx regimen showed promising activity as first-line treatment in fit patients with recurrent/metastatic HNSCC. Further studies are needed to compare the TPEx versus EXTREME regimen in this population. CLINICALTRIALGOV: NCT01289522.

First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: a phase II study (SUPAP) by the French Genitourinary Group (GETUG)†.

BACKGROUND: Papillary renal cell carcinoma (PRCC), type 1 and type 2, represents 10%-15% of renal cell carcinomas (RCC). There is no standard first-line treatment of metastatic PRCC (mPRCC). Anti-angiogenics have shown activity in retrospective studies but no prospective studies in pure papillary histology have been reported, but one with foretinib. PATIENTS AND METHODS: A prospective phase II study evaluated sunitinib in first-line treatment of mPRCC. The primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS: Fifteen and 46 patients, respectively, with type 1 and type 2 mPRCC were enrolled. Using the MSKCC scoring system: 12 (20%), 33 (55%) and 9 (15%) patients were, respectively, in the favourable, intermediate or poor risk group and 7 undetermined. Median follow-up is 51.4 months. In type 1, 2 patients 13% [95% confidence interval (CI) 0.1-30.5] had a partial response (PR), 10 had stable disease (SD) with 5 (33%) ≥12 weeks. In type 2, 5 patients 11% (95% CI 1.9-20.3) had a PR, 25 had SD with 10(22%) ≥12 weeks. Median PFS was 6.6 months (95% CI 2.8-14.8) in type 1 and 5.5 months (95% CI 3.8-7.1) in type 2. Median OS was 17.8 (95% CI 5.7-26.1) and 12.4 (95% CI 8.2-14.3) months, respectively, in type 1 and 2. Safety was as expected with sunitinib for metastatic RCC. CONCLUSION: Sunitinib showed activity in treatment of type 1 and 2 mPRCC but lower than in clear-cell mRCC. Both PFS and OS are longer in type I PRCC. Sunitinib represents an acceptable option in first-line treatment of mPRCC.

[Reirradiations of head and neck cancers: state of the concept and ways of development]. / Ré-irradiations des cancers de la tête et du cou : état du concept et voies de développement.

The treatment of local recurrence or second primary developed in irradiated area in the field of head and neck carcinoma, should be planned and organized through multidisciplinary discussions. The outcome of such a clinical situations benefits from second line and advanced technology treatments. Only a few patients are amenable to salvage surgery, hence radiation therapy, combined or not with chemotherapy, takes a major role in these indications. This overview of the literature describes recent development in this field, aiming to improve local control while the sparing of organ at risk remains an important goal. Radiation therapy is currently implementing major new technologies set to improve external beam irradiation with new concepts on dose, fractionation, intensity modulated radiation therapy and stereotactic approach - as well as in brachytherapy. Apart from dedicated studies, the great heterogeneity of the treated patients should be underlined and taken into consideration. However, current data confirm the feasibility of reirradiation with acceptable local control and toxicity.

Epistaxis in children under the age of two: possible marker of abuse/neglect? A retrospective study in North-Eastern Piedmont hospitals.

AIM: Epistaxis is an extremely common event at all ages; however, under two years of age epistaxis is a very rare event and recent studies carried out in Great Britain concern this event as related to possible non-accidental trauma. To date, no other studies carried out in Italy are available on this topic. METHODS: A file review of all cases of epistaxis occurred in children under the age of 2 who were admitted into the ED in our area over a period of two years was carried out. RESULTS: We have collected data concerning 10 cases of epistaxis occurred in children under 2 years of age with an incidence of 10.4 cases per 10000 accessions to the ED of children under the age of 2. Four of the cases had attendances for head injury or facial trauma. CONCLUSION: The results obtained are higher than the results of the British studies adopting the same methodology, but comparable to their surveillance data on the general population. Through the analysis of the collected data, two correlated assumptions have been made: a possible relationship between epistaxis and neglect, and a relation between epistaxis and domestic accidents.

Phase I dose-escalation study of aflibercept in combination with docetaxel and cisplatin in patients with advanced solid tumours.

BACKGROUND: This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours. METHODS: Patients received intravenous aflibercept 4, 5, or 6 mg kg(-1) with docetaxel and cisplatin (75 mg m(-2) each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination. RESULTS: During the dose-escalation phase (n=16), there were two DLTs of febrile neutropenia (at 4 and 5 mg kg(-1)). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6 mg kg(-1) and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting >3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs. CONCLUSION: Aflibercept 6 mg kg(-1) with docetaxel and cisplatin 75 mg m(-2) every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs.

Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: clinical activity and molecular response (GORTEC 2008-02).

BACKGROUND: Preclinical studies suggest that insulin-like growth factor-1 receptor (IGF-1R) blockage could be a promising therapeutic target in squamous cell carcinoma of the head and neck (SCCHN). Therefore, we investigated the efficacy and toxicity of figitumumab, an anti-IGF-1R monoclonal antibody, in palliative SCCHN. PATIENTS AND METHODS: Patients with palliative SCCHN progressing after platinum-based therapy were treated with figitumumab i.v. 20 mg/kg, every 3 weeks. The primary end point was the disease control rate at 6-8 weeks after treatment initiation. Tumor biopsies and plasma samples were collected before and after figitumumab administration to monitor the molecular response. RESULTS: Seventeen patients were included. Only two patients achieved stable disease at 6-8 weeks. Median overall survival and progression-free survival were 63 and 52 days, respectively. The main grade 3-4 adverse event was hyperglycemia (41%). Translational research showed that figitumumab downregulated IGF-1R at the surface of tumor cells with activation of the epidermal growth factor receptor (EGFR) pathway, as shown by the upregulation of p-EGFR in tumor cells (P=0.016), and an increase in the plasma level of tumor growth factor-alpha (P=0.006). CONCLUSION: Figitumumab monotherapy has no clinically significant activity in unselected palliative SCCHN.

Higher Risk of Severe Drug-Induced Liver Injury among Hispanic HIV-Infected Patients after Initiation of Highly Active Antiretroviral Therapy.

BACKGROUND: Little is known about differences across ethnicities in the development of drug-induced liver injury (DILI) after highly active antiretroviral therapy (HAART) initiation. METHODS: This is a retrospective, longitudinal, comparative, pilot study. DILI within the first year of HAART was evaluated in 50 HIV-infected Hispanics without viral hepatitis who initiated HAART between 2000 and 2009. It was compared to white and black patients (1:1:1) matched by age and CD4 counts. RESULTS: HAART-related DILI of any grade occurred in 30 of 150 (20%) patients and was associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) use (OR 4.49 [95%CI 1.5-13.8]). Severe DILI was significantly more frequent among Hispanics compared to other groups (6% vs. 0%; P = .04). Of the 3 patients with severe DILI, 2 underwent liver imaging and had hepatic steatosis. CONCLUSIONS: Severe DILI within the first year of HAART initiation was infrequent and restricted to Hispanics. Additional studies are needed to determine if fatty liver is involved in the excess of severe DILI observed in this group.

Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial.

BACKGROUND: In the evolution of metastatic castration-resistant prostate cancer (mCRPC), patients present visceral metastases with or without neuroendocrine differentiation in 20% of cases. PATIENTS AND METHODS: We assessed the efficacy and toxicity of a platinum-based chemotherapy regimen in mCRPC patients with either neuroendocrine differentiation defined by high serum levels of chromogranin A (CgA) and neuron-specific enolase (NSE) or visceral metastases. Patients received the combination of carboplatin and etoposide every 3 weeks. Efficacy end points included prostate-specific antigen (PSA) and neuroendocrine marker response, objective response and toxicity. RESULTS: Of the 60 patients included from April 2005 to January 2008, 78.6% had bone metastases, 46.4% had lymph node involvement and 57.1% had liver and/or lung localizations. The objective response rate was 8.9% in the 46 patients with measurable disease. A neuroendocrine response was observed in 31% of cases for NSE and 7% for CgA. The PSA response rate was 8%. The most common grade 3-4 treatment-related toxic effects were neutropenia (65.5%), thrombocytopenia (32.7%) and anemia (27.3%). There was 7.2% febrile neutropenia, with one toxicity-related death. The median follow-up was 9.3 months [95% confidence interval (CI) 0.2-27.1] and the median overall survival 9.6 months (95% CI 8.7-12.7). CONCLUSION: The benefit-risk ratio of this regimen seems unfavorable due to poor response and high toxicity.

[Polyuria and polydipsia in a 5 year-old child: diagnostic problems]. / Esordio di poliuria e polidipsia in una bambina di 5 anni: le problematiche della diagnosi differenziale.

Polyuria and polydipsia could be present in three groups of diseases; polydipsia psicogena characterized by an excessive water intake, central diabetes insipidus (CDI) with a defect in the production of AVP and nephrogenic diabetes insipidus in which a defect in the renal response to vasopressin is present. In particular, CDI can be caused by lesions like germinoma and craniopharyngioma, Langerhans'cell histiocytosis, inflammatory, autoimmune and vascular diseases, trauma resulting from surgery or an accident; and in rare cases, genetic defects in the synthesis of vasopressin that are inherited as autosomal dominant or X-linked recessive traits. However, 30% to 50% of cases are considered idiopathic. Nevertheless, 30-50% of cases is considered idiopathic. Here we present the case of a 5.5 year-old female patient, referred to our Department of Endocrinology Surgery for polyuria and polydipsia. Hormonal tests demonstrated the presence of CDI with normal anterior pituitary function. Magnetic resonance imaging showed the lack of hyperintensity of posterior pituitary. Pituitary stalk was median and of regular volume. Diagnosis of CDI has been confirmed and therapy has been started with desmopressin (Minirin) 0.2 mg/die. During the follow-up the patient was in good conditions, presented an adequate hydro-electrolytic balance and normal growth velocity. Anterior pituitary function was normal and MR remained stable. This case report highlights problems concerning differential diagnosis and the importance of a careful follow-up which must involve the whole family.

Phase I clinical and pharmacokinetic study of E7070, a novel sulfonamide given as a 5-day continuous infusion repeated every 3 weeks in patients with solid tumours. A study by the EORTC Early Clinical Study Group (ECSG).

A single-agent dose-escalating phase I study on the novel sulfonamide E7070 was performed to determine the toxicity profile and the recommended dose for phase II studies. The pharmacokinetic profile of E7070 was also determined. E7070 was administered as a continuous infusion over 5 days repeated every 3 weeks. 27 patients were treated at doses ranging from 6 to 200 mg/m(2)/day. As with other administration schedules, the dose-limiting toxicities were dose-dependent, reversible neutropenia and thrombocytopenia. Although no objective responses were observed, seven patients had stable disease. E7070 displayed a non-linear pharmacokinetic profile, especially at dose-levels greater than 24 mg/m(2)/day, with a reduction in clearance and an increase in the half-life at the higher dose levels. The risk of myelosuppression became significant with an AUC greater than 4000 microg h/ml. The recommended dose of E7070 for further studies is 96 mg/m(2)/day when administered on a 5-day continuous infusion schedule every 3 weeks.

[Interpretation of the CA125 kinetics during first line chemotherapy of the ovarian cancer: methodological aspects and characteristic profiles]. / Interprétation des cinétiques du CA125 sous chimiothérapie de première ligne des cancers de l'ovaire: aspects méthodologiques et profils caractéristiques.

Mathematical analysis of CA125 kinetics during first line chemotherapy allows calculation of various biologic parameters which are powerful indicators of the therapeutic efficiency. The purpose of this study is to present an original method of interpretation of CA125 kinetics based on both CA125 profile and its half-life value. The first part of this study reviews the practical modalities of CA125 kinetics analysis, the methods of calculation of the biologic parameters as well as the guidelines of interpretation. The second part of this work is dedicated to the presentation of CA125 profile characteristics in responders to chemotherapy, partially or totally nonresponders to chemotherapy, tumoral growth under treatment and tumor lysis syndrome.