Palifermin for oral mucositis after intensive therapy for hematologic cancers

BACKGROUND: Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment. We tested the ability of palifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy. METHODS: This double-blind study compared the effect of palifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers; 106 patients received palifermin (60 microg per kilogram of body weight per day) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy (fractionated total-body irradiation plus high-dose chemotherapy) and after autologous hematopoietic stem-cell transplantation. Oral mucositis was evaluated daily for 28 days after transplantation. RESULTS: The incidence of oral mucositis of World Health Organization (WHO) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group (P\u3c0.001). Among patients with this degree of mucositis, the median duration of mucositis was 6 days (range, 1 to 22) in the palifermin group and 9 days (range, 1 to 27) in the placebo group. Among all patients, regardless of the occurrence of mucositis, the median duration of oral mucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) in the palifermin group and 9 days (range, 0 to 27) in the placebo group (P\u3c0.001). As compared with placebo, palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis (20 percent vs. 62 percent, P\u3c0.001), patient-reported soreness of the mouth and throat (area-under-the-curve score, 29.0 [range, 0 to 98] vs. 46.8 [range, 0 to 110]; P\u3c0.001), the use of opioid analgesics (median, 212 mg of morphine equivalents [range, 0 to 9418] vs. 535 mg of morphine equivalents [range, 0 to 9418], P\u3c0.001), and the incidence of use of total parenteral nutrition (31 percent vs. 55 percent, P\u3c0.001). Adverse events, mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration, were mild to moderate in severity and were transient. CONCLUSIONS: Palifermin reduced the duration and severity of oral mucositis after intensive chemotherapy and radiotherapy for hematologic cancers

Palifermin for Oral Mucositis after Intensive Therapy for Hematologic Cancers

BACKGROUND Oral mucositis is a complication of intensive chemotherapy and radiotherapy with no effective treatment. We tested the ability ofpalifermin (recombinant human keratinocyte growth factor) to decrease oral mucosal injury induced by cytotoxic therapy. METHODS This double-blind study compared the effect ofpalifermin with that of a placebo on the development of oral mucositis in 212 patients with hematologic cancers; 106 patients received palifermin (60 μg per kilogram ofbody weight per day) and 106 received a placebo intravenously for three consecutive days immediately before the initiation of conditioning therapy (fractionated total-body irradiation plus high-dose chemotherapy) and after autologous hematopoietic stem-cell transplantation. Oral mucositis was evaluated daily for 28 days after transplantation. RESULTS The incidence oforal mucositis of World Health Organization (WHO) grade 3 or 4 was 63 percent in the palifermin group and 98 percent in the placebo group (P<0.001). Among patients with this degree of mucositis, the median duration of mucositis was 6 days (range, 1 to 22) in the palifermin group and 9 days (range, 1 to 27) in the placebo group. Among all patients, regardless ofthe occurrence of mucositis, the median duration of oral mucositis of WHO grade 3 or 4 was 3 days (range, 0 to 22) in the palifermin group and 9 days (range, 0 to 27) in the placebo group (P<0.001). As compared with placebo, palifermin was associated with significant reductions in the incidence of grade 4 oral mucositis (20 percent vs. 62 percent, P<0.001), patient-reported soreness of the mouth and throat (area-under-the-curve score, 29.0 [range, 0 to 98] vs. 46.8 [range, 0 to 110]; P<0.001), the use ofopioid analgesics (median, 212 mg ofmorphine equivalents [range, 0 to 9418] vs. 535 mg of morphine equivalents [range, 0 to 9418], P<0.001), and the incidence of use of total parenteral nutrition (31 percent vs. 55 percent, P<0.001). Adverse events, mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration, were mild to moderate in severity and were transient CONCLUSIONS Palifermin reduced the duration and severity oforal mucositis after intensive chemotherapy and radiotherapy for hematologic cancers

Depression in medical students: insights from a longitudinal study

Background: Factors associated with depression of medical students are poorly understood. The purpose of this study is to determine the prevalence of depression in medical students, its change during the course, if depression persists for affected students, what are the factors associated with depression and how these factors change over time. Methods: A prospective, longitudinal observational study was conducted at the Medical School of the University of Minho, Portugal, between academic years 2009-2010 to 2012-2013. We included students who maintained their participation by annually completing a questionnaire including Beck Depression Inventory (BDI). Anxiety and burnout were assessed using the State Trait Anxiety Inventory and Maslach Burnout Inventory. Surveys on socio-demographic variables were applied to evaluate potential predictors, personal and academic characteristics and perceived difficulties. ANOVA with multiple comparisons were used to compare means of BDI score. The medical students were organized into subgroups by K-means cluster analyses. ANOVA mixed-design repeated measurement was performed to assess a possible interaction between variables associated with depression. Results: The response rate was 84, 92, 88 and 81% for academic years 2009-2010, 2010-2011,2011-2012 and 2012/2013, respectively. Two hundred thirty-eight medical students were evaluated longitudinally. For depression the prevalence ranged from 21.5 to 12.7% (academic years 2009/2010 and 2012/2013). BDI scores decreased during medical school. 19.7% of students recorded sustained high BDI over time. These students had high levels of trait-anxiety and choose medicine for anticipated income and prestige, reported more relationship issues, cynicism, and decreased satisfaction with social activities. Students with high BDI scores at initial evaluation with low levels of trait-anxiety and a primary interest in medicine as a career tended to improve their mood and reported reduced burnout, low perceived learning problems and increased satisfaction with social activities at last evaluation. No difference was detected between men and women in the median BDI score over time. Conclusions: Our findings suggest that personal factors (anxiety traits, medicine choice factors, relationship patterns and academic burnout) are relevant for persistence of high levels of BDI during medical training. Medical schools need to identity students who experience depression and support then, as early as possible, particularly when depression has been present over time.info:eu-repo/semantics/publishedVersio

No Difference in Survival or Long-Term Disease Outcomes in Palifermin-Treated Patients with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplantation

Abstract Background: Oral mucositis is an adverse effect of myeloablative therapy which has serious clinical and economic consequences as well as a negative impact upon quality of life. The duration and severity of oral mucositis can be reduced by administering palifermin to patients with hematological malignancies receiving myeloablative therapy and undergoing hematopoietic stem cell transplantation (HSCT). However, we still require additional data on the long-term disease outcomes of patients treated with palifermin. Therefore we present here the long-term, safety data for palifermin-treated HSCT patients followed up for approximately 60 months after the last palifermin dose. Methods: The long-term safety data were collected during the follow-up phase of 4 parent trials where patients had received at least one dose of palifermin or placebo. Study assessments included overall survival (OS), progression-free survival (PFS), and secondary malignancies. Assessments were made at 6-month intervals during year 1 and annually thereafter until death or loss to follow-up. Kaplan-Meier curves for overall survival and PFS were calculated and the treatment groups were compared using stratified log-rank test. Results: Altogether 662 patients were randomized to treatment and received either palifermin or placebo (421 palifermin, 241 placebo); 538 patients entered the follow-up study (342 palifermin, 196 placebo). The median follow-up time for patients alive at last visit was 49.8 months (palifermin N=290) and 49.5 months (placebo N=169). There were 131 (32%) and 72 (30%) deaths in the palifermin and placebo groups, respectively. The overall survival curves were similar for both groups (p=0.717). Disease progression occurred in 167 (41%) palifermin- and 87 (36%) placebo-treated patients; the difference in PFS between the two groups was non-significant (p=0.280). Secondary malignancies were observed in 8% of patients in both groups: the incidence of secondary hematologic malignancies was 4% (palifermin: 14/342) versus 5% (placebo: 10/196) while the incidence of solid tumors was 2% in both groups. Conclusion: The results of this 60-month follow-up study indicate that long-term disease outcomes are not affected by administering palifermin to patients with hematological malignancies who are receiving myeloablative therapy and undergoing HS. There was no difference in OS and PFS between the palifermin and placebo groups. Furthermore there was no difference in the incidence of secondary malignancies between the two patient groups. The incidence of secondary hematologic malignancies and solid tumors was low, comparable between groups, and within the expected range for this patient population