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Acceptable Safety Profile (acceptable + safety_profile)
Selected AbstractsClofarabine in the treatment of poor risk acute myeloid leukaemiaHEMATOLOGICAL ONCOLOGY, Issue 3 2010Janusz Krawczyk Abstract Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24,76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17,120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy to treat gastric cancer with ascites and/or peritoneal carcinomatosis: Results from a Chinese centerJOURNAL OF SURGICAL ONCOLOGY, Issue 6 2010Xiao-Jun Yang MD Abstract Background This work was to evaluate cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (GC). Methods CRS and HIPEC were performed on 28 GC patients with peritoneal carcinomatosis (PC) and/or malignant ascites, with survival and perioperative safety as study endpoints. Results A total of 30 CRS and HIPEC procedures were performed. Cytoreduction scores ratings (CCR) were CCR-0 in 11 (39.2%), CCR-1 in 6 (21.4%), CCR-2 in 8 (28.8%), and CCR-3 in 3 (10.6%) cases. The 6-, 12-, 18-, and 24-month survival rates were 75%, 50%, 43%, and 43%, respectively. The median survivals of patients with PCI ,20 and high PCI >20 were 27.7 months (95% CI 15.2,40.3 months) and 6.4 months (95% CI 3.8,8.9 months) (P,=,0.000). The estimated median survival for patients with CCR-0, CCR-1, and CCR-2 and 3 were 43.4 months (95% CI, 26.9,59.9 months), 9.5 months (95% CI 6.4,12.6 months), and 7.5 months (95% CI 3.0,13.6 months) (P,=,0.001, CCR0 vs. CCR1-3). No perioperative death but 1 (3.6%) serious adverse event occurred. Conclusions CRS plus HIPEC could offer survival advantage for selected GC patients with PC and/or ascites, with acceptable safety profile. J. Surg. Oncol. 2010; 101:457,464. © 2010 Wiley-Liss, Inc. [source] Imiquimod 5% cream is an acceptable treatment option for external anogenital warts in uncircumcised malesJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2002RD Maw Abstract Objectives To determine the safety and efficacy of imiquimod (AldaraÔ) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. Methods An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. Results Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. Conclusions Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males. [source] Fumagillin for Treatment of Intestinal Microsporidiosis in Renal Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010L. Champion We report 10 cases of intestinal microsporidiosis due to Enterocytozoon bieneusi in renal transplant (RT) recipients who were treated with fumagillin. All patients presented with afebrile subacute diarrhea (median of 2 weeks), associated with abdominal cramps (n = 5), and weight loss (n = 6), a mean of 68 months after RT. The diagnosis was made by the identification of microsporidial spores in stools with the use of appropriate staining and confirmed by a specific polymerase chain reaction assay for E. bieneusi in 7 patients. Median CD4 cell count was 292 cells/mm3. All patients received a median of 14 days of oral fumagillin (20 mg tid), and four patients also discontinued or tapered their immunosuppressive regimen (mycophenolate mofetil in 3, and azathioprine in 2). Clinical symptoms resolved rapidly with the clearance of microsporidial spores from stools in all patients. A severe but reversible thrombocytopenia was observed in one patient during fumagillin therapy, and another patient presented with abdominal cramps. Trough levels of tacrolimus measured in seven patients dropped below 5 ng/mL in six of them after 7,14 days of fumagillin. Intestinal microsporidiosis can cause subacute diarrhea in RT recipients. Fumagillin is an effective treatment with an acceptable safety profile, but monitoring of tacrolimus levels is warranted. [source] Sugammadex in clinical practiceANAESTHESIA, Issue 2009R. K. Mirakhur Summary The availability of sugammadex allows greater flexibility in the use of rocuronium and vecuronium during anaesthesia and surgery. The neuromuscular block induced by both drugs can be reversed from both superficial and deep levels of block by adjusting the dose of sugammadex. The dose of sugammadex for reversal of shallow block produced by these neuromuscular blocking drugs is approximately 2 mg.kg,1 and for deep block the dose is 4 mg.kg,1. A larger dose of sugammadex (16 mg.kg,1) administered 3 min after the neuromuscular blocking drug allows rapid reversal of a neuromuscular block induced by 1,1.2 mg.kg,1 of rocuronium, thereby raising the possibility of using rocuronium as a replacement for suxamethonium. The use of sugammadex has not been reported to be associated with recurrence of block provided a dose that is adequate for reversal has been used. Sugammadex appears to have an acceptable safety profile. There are no requirements for dose adjustment for age or the use of potent volatile anaesthetic agents. [source] Superior efficacy of a Cremophor-free albumin-bound paclitaxel compared with solvent-based paclitaxel in Chinese patients with metastatic breast cancerASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 3 2009Zhong-Zhen GUAN Abstract Aim: In a previous study, a 130-nm nanoparticle albumin-bound paclitaxel (nab -paclitaxel) demonstrated improved efficacy and safety profile compared with solvent-based paclitaxel (sb-paclitaxel) in Caucasian patients with metastatic breast cancer (MBC). The aim of the present randomized study was to compare the response rates and safety profile of nab -paclitaxel with sb-paclitaxel in Chinese patients with MBC. Methods: In the present open-label, multicenter study, 210 patients with MBC were randomly assigned to receive nab -paclitaxel 260 mg/m2 intravenously (i.v.) over 30 min every 3 weeks (q3w) with no premedication or sb-paclitaxel 175 mg/m2 i.v. over 3 h q3w with standard premedication. Results: The overall response rate was 54 and 29% in patients treated with nab -paclitaxel and sb-paclitaxel, respectively (P < 0.001). nab -paclitaxel induced a higher response rate in patients who were <65 years old, patients who were receiving first-line therapy, patients who had no prior anthracycline therapy, patients who had , or >3 metastatic lesions, and patients who had visceral disease. The progression-free survival (PFS) period was 7.6 months for nab -paclitaxel and 6.2 months for sb-paclitaxel (P = 0.118). Despite the 49% higher paclitaxel dose in patients receiving nab -paclitaxel compared with patients receiving sb-paclitaxel, the safety profile was similar in both treatment groups. The most common grades 3 and 4 adverse event (AE) in both arms was neutropenia. The most common grade 3 nonhematologic AE was peripheral neuropathy, and no grade 4 peripheral neuropathy was observed. Conclusion: Compared with sb-paclitaxel, nab -paclitaxel demonstrated superior efficacy, an acceptable safety profile, and a trend toward increased PFS in patients with MBC. [source] Pharmacokinetics, immunogenicity and bioactivity of the therapeutic antibody catumaxomab intraperitoneally administered to cancer patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2010Peter Ruf WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , The trifunctional antibody catumaxomab is a highly effective anti-cancer therapeutic that is administered to patients suffering from malignant ascites intraperitoneally (i.p.) in microgram (µg) doses. So far, no clinical pharmacokinetic data are available. WHAT THIS STUDY ADDS , Catumaxomab attains effective local concentrations in the ascites fluid and shows low systemic exposure with an acceptable safety profile confirming the appropriateness of the i.p. application scheme. AIMS Catumaxomab is the first EMEA approved trifunctional anti-EpCAM×anti-CD3 antibody for the treatment of cancer patients with malignant ascites. A phase II pharmacokinetic study was conducted to determine local and systemic antibody concentrations and anti-drug antibody (ADA) development. METHODS Thirteen cancer patients with symptomatic malignant ascites were treated with four ascending doses of 10, 20, 50, and 150 µg catumaxomab intraperitoneally (i.p.) infused on days 0, 3, 6 or 7 and 10. The pharmacokinetics of catumaxomab were studied by implementation of supportive data from a non clinical mouse tumour model. Additionally, ADA development was monitored. RESULTS Ten out of 13 patients were evaluable for pharmacokinetic analysis. Catumaxomab became increasingly concentrated in ascites during the course of treatment, attaining effective concentrations in the ng ml,1 range. Catumaxomab remained immunologically active even after several days in the circulation. The observed systemic catumaxomab exposure was low (<1%), with a maximal median plasma concentration (Cmax) of 403 pg ml,1. The mean elimination half-life in the plasma was 2.13 days. All patients developed ADA, but not before the last infusion. High observed inter-individual variability and low systemic exposure may be explained by the inverse correlation between tumour burden, effector cell numbers and systemic antibody bioavailability as demonstrated in a defined mouse tumour model. CONCLUSIONS Based on the high and effective local concentrations, low systemic exposure and acceptable safety profile, we confirmed that the i.p. application scheme of catumaxomab for the treatment of malignant ascites is appropriate. [source] Phase I study of TLR9 agonist PF-3512676 in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancerCANCER SCIENCE, Issue 1 2010Kazuhiko Yamada This phase I, open-label study investigated the Toll-like receptor 9 agonist, PF-3512676, in combination with carboplatin and paclitaxel in Japanese patients with advanced, non-small-cell lung cancer (NSCLC). Patients (n = 12) with treatment-naive stage IIIB or IV NSCLC received single-agent PF-3512676 subcutaneously once during the first 7 days (monotherapy phase) in three escalating dose levels (0.1, 0.2, and 0.4 mg/kg) followed by a combination phase during which patients received 0.1 or 0.2 mg/kg PF-3512676 subcutaneously on days 8 and 15 of each 3-week cycle of carboplatin (area under the curve, 6 mg × min/mL) and paclitaxel (200 mg/m2). Safety and pharmacokinetics of PF-3512676 were assessed during monotherapy and combination therapy phases. PF-3512676 was tolerable as monotherapy or in combination with chemotherapy in patients with NSCLC. Most common treatment-related, non-hematologic adverse events (AEs) throughout the study were injection-site reactions (n = 12, 100%) and flu-like symptoms (n = 11, 91.7%) that were each grade 1 or 2 in all but one patient. All patients experienced neutropenia and leukopenia (,grade 3 in 11 [91.7%] and seven [58.3%] patients, respectively). One patient in dose level 2 had a dose-limiting toxicity: grade 3 rash and grade 3 increase in ,-glutamyltransferase during combination therapy. Mean PF-3512676 half-life ranged from 4.8 to 21.6 h (longer with higher doses). Four (33%) patients had objective responses (one complete response, three partial responses), and seven (58%) patients achieved stable disease. PF-3512676 as monotherapy and in combination with chemotherapy had an acceptable safety profile in Japanese patients with treatment-naive NSCLC. (Cancer Sci 2009) [source] | ||||||||||