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Response Duration (response + duration)
Selected AbstractsSex Differences in Ethanol-Induced Hypothermia in Ethanol-Naïve and Ethanol-Dependent/Withdrawn RatsALCOHOLISM, Issue 1 2009Anna N. Taylor Background:, Human and animal findings indicate that males and females display major differences in risk for and consequences of alcohol abuse and alcoholism. These differences are in large part mediated by sex-specific hormonal environments. Gonadal and adrenal secretory products are known to modulate the neurobehavioral responses of ethanol (EtOH) dependence and withdrawal. However, the effects of these steroids on physiological adaptations, such as thermoregulation, are less well established. To study the role of sex-related hormones in mediating sex differences in the hypothermic response to acute challenge with EtOH, we compared the EtOH-induced hypothermic responses of EtOH-naïve male and female rats and EtOH-dependent (on the third day of withdrawal) male and female rats before (intact) and after depletion of all gonadal and adrenal steroids by gonadectomy (GDX) with or without adrenalectomy (ADX). Methods:, Intact and GDX male and female rats, with or without ADX, were fed an EtOH-containing liquid diet for 15 days while control (EtOH-naïve) rats were pairfed the isocaloric liquid diet without EtOH or fed normal rat chow and water. On the third day of withdrawal from the EtOH diet we tested the hypothermic response to EtOH challenge (1.5 g/kg BWt, ip). Blood alcohol content (BAC) and corticosterone (CORT) content were analyzed in a separate series of intact and GDX males and females with and without ADX in response to the EtOH challenge. Results:, Ethanol-induced hypothermia was significantly greater and its duration significantly longer in intact males than females when subjects were EtOH-naïve. EtOH-induced hypothermia was significantly greater in intact females than males by the third day of withdrawal from EtOH dependence. GDX in males significantly shortened the duration of the hypothermic response and tended to blunt EtOH-induced hypothermia while response duration was significantly extended by GDX in females that tended to enhance EtOH-hypothermia. EtOH-induced hypothermia was significantly enhanced and its duration significantly lengthened by combined GDX and ADX in EtOH-naïve and -withdrawn males and by combined GDX and ADX in EtOH-naïve but not EtOH-withdrawn females. These differential EtOH-induced hypothermic responses did not appear to be caused by differences in EtOH handling among the groups. The absence of adrenal activation by EtOH in the GDX,ADX males and females contributes to their enhanced EtOH-induced hypothermic responses. Conclusions:, These results implicate the direct and indirect effects of removal of gonadal and adrenal secretory products as mediators of the thermoregulatory actions of EtOH. [source] A Phase II intra-patient dose-escalation trial of weight-based darbepoetin alfa with or without granulocyte-colony stimulating factor in myelodysplastic syndromes,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2009Jason Gotlib This Phase II study evaluated darbepoetin alfa (DA) in 24 patients with predominantly low or intermediate-1 risk myelodysplastic syndrome (MDS). Intra-patient dose escalation of DA was undertaken in three 6-week dose cohorts until a major erythroid response was achieved: 4.5 mcg/kg/week, 9 mcg/kg/week, and 9 mcg/kg/week plus granulocyte-colony stimulating factor (G-CSF) 2.5 mcg/kg twice weekly. Patients with refractory anemia with ringed sideroblasts (RARS) commenced DA at 9 mcg/kg/week. The weight-based dosing regimen translated into a median starting DA dose of 390 mcg/week. Erythroid responses were observed in 16/24 patients (67%; 12 major and 4 minor), with a median response duration of 11 months in major responders. Addition of G-CSF generated a major erythroid response in 7/15 patients (47%) who suboptimally responded to DA alone. DA was well tolerated, except for worsening of baseline mild hypertension and renal insufficiency in one patient with diabetes. IPSS score <0.5 and RBC transfusions <2 units/month increased the probability of an erythroid response. A minority of subjects (12%) developed low-level non-neutralizing anti-DA antibodies. Our data indicate that weekly weight-based dosing of DA, with the addition of G-CSF in selected individuals, can be an effective erythropoietic option in a high proportion of lower-risk MDS patients. Am. J. Hematol, 2009. © 2008 Wiley-Liss, Inc. [source] Rituximab in the adjuvant treatment of pemphigus vulgaris: a prospective open-label pilot study in five patientsBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2007M.S.Y. Goh Summary Background, Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B lymphocytes. There are reports of its efficacy in the treatment of autoimmune diseases, including pemphigus. Objectives, Prospectively to evaluate the efficacy of rituximab as adjuvant treatment for pemphigus vulgaris (PV). Methods, Patients with PV were treated with intravenous rituximab (375 mg m,2) weekly for 4 weeks in this prospective open-label pilot study. Other concurrent immunosuppression was continued. Results, Of five patients, one achieved complete remission and was able to cease all medication, while two achieved clearance of clinical lesions but continued on systemic therapy. Two patients had progressive disease. Time to response was 2,8 months, with a 13- to 18-month response duration. Response was associated with reduction in serum antiepithelial antibodies. Two patients had significant infectious complications (one developed community-acquired pneumonia associated with delayed-onset neutropenia and the other developed cytomegalovirus infection). Conclusions, Rituximab has shown efficacy in the treatment of PV. Patients on multiple immunosuppressives should be closely monitored for infectious complications. [source] Radioembolization of colorectal hepatic metastases using yttrium-90 microspheresCANCER, Issue 9 2009Mary F. Mulcahy MD Abstract BACKGROUND: The objective of the current study was to determine the safety and efficacy of Yttrium-90 (Y90) microsphere treatment in patients with liver-dominant colorectal metastases. METHODS: Seventy-two patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 120 Gray (Gy). Safety and toxicity were assessed using version 3 of the National Cancer Institute Common Terminology Criteria. Response was assessed by anatomic imaging and positron emission tomography (PET). Survival from the diagnosis of hepatic metastases and first treatment were estimated using the Kaplan-Meier method. Substratification analyses were performed. RESULTS: The median dose delivered was 118 Gy. Treatment-related toxicities included fatigue (61%), nausea (21%), and abdominal pain (25%). Grade 3 and 4 bilirubin toxicities were observed in 9 of 72 patients (12.6%). The tumor response rate was 40.3%. The median time to hepatic progression was 15.4 months, and the median response duration was 15 months. The PET response rate was 77%. Overall survival from the first Y90 treatment was 14.5 months. Tumor replacement (,25% vs >25%) was associated with significantly greater median survival (18.7 months vs 5.2 months). The presence of extrahepatic disease was associated negatively with overall survival (7.9 months vs 21 months). Overall survival from the date of initial hepatic metastases was 34.6 months. A subset analysis of patients who had an Eastern Cooperative Oncology Group performance status of 0 demonstrated a median survival of 42.8 months and 23.5 months from the time of hepatic metastases and Y90 treatment, respectively. CONCLUSIONS: Y90 liver therapy appears to provide sustained disease stabilization with acceptable toxicity. Asymptomatic patients with preserved liver function at the time of Y90 appeared to benefit most from treatment. Cancer 2009. © 2009 American Cancer Society. [source] Activity of cladribine combined with cyclophosphamide in frontline therapy for chronic lymphocytic leukemia with 17p13.1/TP53 deletion,CANCER, Issue 1 2009Report From the Polish Adult Leukemia Group Abstract BACKGROUD: The 17p13.1 deletion that causes loss of the p53-encoding TP53 gene is the most powerful predictor of a poor response to conventional therapy and shortened survival in patients with chronic lymphocytic leukemia (CLL). The results of this study have demonstrated that the cladribine and cyclophosphamide regimen may improve treatment results in this poor-risk patient population. METHODS: In this study, the authors retrospectively analyzed the efficacy and toxicity of 2-CdA with cyclophosphamide combination (the CC regimen) in 20 patients with previously untreated B-cell CLL who had 17p13.1 deletion reported to the Polish Adult Leukemia Group (PALG) registry. The CC regimen consisted of 2-CdA at a dose of 0.12 mg/kg and cyclophosphamide at a dose of 250 mg/m2 given intravenously for 3 consecutive days. The CC cycles were repeated at 28-day intervals for up to 6 cycles. RESULTS: Overall, 16 of 20 patients (80%) responded to CC therapy, including 10 patients (50%) who obtained a complete response and 6 patients (30%) who obtained a partial response. The median progression-free survival reached 23 months (95% confidence interval, 5-41 months). The overall survival probability at 2 years was 52.5% (95% confidence interval, 26%-79%). Treatment toxicity generally was acceptable. Infections were the most common grade 3/4 complications and occurred in 6 patients (30%). CONCLUSIONS: In this retrospective analysis, the results demonstrated that the CC regimen produced a relatively high response rate in patients with previously untreated CLL who had 17p13.1/TP53 deletion, although the response duration and survival were not satisfactory. It is possible that a combination of the CC regimen with p53-independent agents may improve treatment results in this poor-risk patient population. Cancer 2009. © 2008 American Cancer Society. [source] Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapyCANCER, Issue 7 2008Pieter Sonneveld MD Abstract BACKGROUND Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In the current analysis, they determined 1) the efficacy of PLD plus bortezomib versus bortezomib alone in patients with MM who had failed on prior thalidomide/lenalidomide (immunomodulatory drug [IMiD]) treatment and 2) the efficacy and safety profile of PLD plus bortezomib in IMiD-exposed and IMiD-naive patients. METHODS This prespecified analysis included 646 patients who were randomized to receive either PLD with bortezomib (n = 324; 194 IMiD-naive patients and 130 IMiD-exposed patients) or bortezomib alone (n = 322; 184 IMiD-naive patients and 138 IMiD-exposed patients). The primary efficacy endpoint was TTP, and secondary endpoints included overall survival, response rate, and safety. RESULTS The median TTP was significantly longer with PLD plus bortezomib compared with bortezomib alone in IMiD-exposed patients (270 days vs 205 days). No statistical difference was noted with respect to TTP between IMiD-naive (295 days) versus IMiD-exposed (270 days) subgroups who received PLD plus bortezomib. A sustained trend favoring combination therapy was observed in analyses of overall survival. In patients who achieved a response, the response duration was comparable for IMiD-naive patients and IMiD-exposed patients in the combination treatment group and lasted a median of 310 days and 319 days, respectively. The incidence of grade 3/4 adverse events was similar with PLD plus bortezomib regardless of prior IMiD exposure. CONCLUSIONS A significantly prolonged TTP was observed with combined PLD plus bortezomib combination therapy compared with bortezomib alone despite prior IMiD exposure. For the combination treatment arm in the IMiD-naive and IMiD-exposed subgroups, TTP was comparable. Similarly, the safety profile of the PLD plus bortezomib combination was unaltered by prior IMiD exposure. Cancer 2008. © 2008 American Cancer Society. [source] Combining endocrine agents with chemotherapy: Which patients and what sequence?,CANCER, Issue S3 2008Kathleen I. Pritchard MD Abstract In metastatic breast cancer, attempts to improve response to therapy by combining hormones and chemotherapy began in the 1970s. Since then, several randomized trials comparing single-agent hormone therapy or chemotherapy versus sequential combinations of these agents have been performed. In the majority of those studies, an increased response rate or an increased time to progression was observed when chemotherapy was added to hormone therapy or when hormone therapy was added to chemotherapy. However, in few of those trials was the increased response rate statistically significant or the response duration significantly prolonged, and no studies reported an improvement in overall survival. Furthermore, the studies did not make the correct comparisons of 1) hormone therapy alone followed by chemotherapy alone versus hormone therapy and chemotherapy given concurrently or 2) chemotherapy alone followed by hormone therapy versus concurrent chemotherapy and hormone therapy. To truly be advantageous, concurrent treatment should provide an increased response rate and response duration compared with the added or overall response rate and response duration of the same agents used sequentially. In the adjuvant setting, the timing and sequencing of hormone therapy and chemotherapy also has not been studied well. However, it has been accepted widely that adjuvant chemotherapy should be completed before beginning tamoxifen. No trials examining concurrent versus sequential treatment have been performed with hormone therapy and chemotherapy in the premenopausal setting or with aromatase inhibitors and chemotherapy in postmenopausal women. Considering the demonstrated importance of the timing of chemotherapy and tamoxifen in the postmenopausal setting, these questions should be explored further. Cancer 2008. © 2007 American Cancer Society. [source] A randomized trial of liposomal daunorubicin and cytarabine versus liposomal daunorubicin and topotecan with or without thalidomide as initial therapy for patients with poor prognosis acute myelogenous leukemia or myelodysplastic syndromeCANCER, Issue 5 2003Jorge Cortes M.D. Abstract BACKGROUND Because angiogenesis may play a role in the pathogenesis of acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), and thalidomide (Th) has shown significant anti-angiogenic activity, this study was designed to investigate the potential role of Th in the treatment of patients with AML and MDS and the possible role of a non,ara-C-containing regimen. METHODS Adults with AML or high-risk MDS and cytogenetic abnormalities other than inv (16), t(8;21), -Y or -X were randomized to receive liposomal daunorubicin (DNX) and ara-C (DA) or DNX and topotecan (DT). Within each arm, patients were randomized to receive chemotherapy alone (DA or DT) or with thalidomide (DATh or DTTh). Vascular endothelial growth factor (VEGF) plasma levels and microvascular density was measured before and after therapy. Eighty-four patients (median age, 65 years; range, 27,84 years) were treated. RESULTS None of 11 patients treated with DT or DTTh responded and these arms were closed. Seventeen of 37 patients treated with DA and 15 of 36 treated with DATh achieved an early complete remission. Median complete response duration was 38 and 34 weeks (P = 0.57) and median survival 35 and 28 weeks (P = 0.15), respectively. Patients with high pretreatment VEGF levels had an inferior survival. There was no significant difference in the changes in VEGF levels or microvascular density after treatment in patients who did versus those who did not receive thalidomide. CONCLUSIONS The authors concluded that thalidomide in combination with chemotherapy does not result in clinical benefit in patients with AML or high-risk MDS. Cancer 2003;97:1234,41. © 2003 American Cancer Society. DOI 10.1002/cncr.11180 [source] | ||||||||||