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International Units (international + unit)
Selected AbstractsInhibitor development in patients receiving recombinant factor VIII (Recombinate rAHF/Bioclate®): a prospective pharmacovigilance studyHAEMOPHILIA, Issue 5 2004B. M. Ewenstein Summary., Clinical trials to date have not been adequately powered to assess comparatively infrequent events such as inhibitor development in previously treated patients (PTPs). Comprehensive large-scale pharmacovigilance studies can be useful for this purpose. We prospectively collected inhibitor development reports worldwide among recipients of Recombinate rAHF recombinant factor VIII (rFVIII), also formerly distributed under the product name Bioclate®, for the entire postlicensure period from 1993 through 2002. To determine level of exposure to rFVIII we also compiled the Recombinate rAHF/Bioclate International Units (IU) distributed annually. To estimate inhibitor incidence separately for previously untreated or minimally treated patients (PUPs) with 1,50 exposure days and PTPs with >50 exposure days, we used haemophilia A incidence and prevalence data and pooled mean annual rFVIII consumption per PUP and PTP from international multicentre prospective clinical trials. Documented inhibitor cases totalled 89, and the total quantity of Recombinate rAHF/Bioclate rFVIII distributed was 6.48 ×109 IU. No lot association or other clustering of inhibitor events was evident in PTPs. The incidence of all reported inhibitors, expressed as a percentage of patients treated, was 11.9% (CI: 5.05,28.0%) for PUPs when compared with 0.123% (CI: 0.030,0.512%) for PTPs. The rates for high-titre inhibitors (>5 BU) only were 5.96% (CI: 3.00,11.8%) for PUPs and 0.0554% (CI: 0.0113,0.271%) for PTPs. Thus, incidence rates for both all inhibitors and high-titre inhibitors in PTPs were 1% of the corresponding rates in PUPs. Data from prospective PUP clinical trials involving intensive active monitoring suggest that true inhibitor incidence may be approximately twice that estimated in this pharmacovigilance study. Nevertheless, inhibitor development in PTPs receiving Recombinate rAHF/Bioclate is infrequent. [source] Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioidsCANCER, Issue 4 2004Arun Rajagopal M.D. Abstract BACKGROUND Profound hypogonadism has been noted in patients receiving intrathecal opioids. The purpose of the current study was to determine whether chronic consumption of oral opioids by male survivors of cancer also would lead to central hypogonadism and whether this hypogonadism was associated with symptoms of sexual dysfunction, fatigue, anxiety, and depression. METHODS A case,control study was conducted at The University of Texas M. D. Anderson Cancer Center (Houston, TX), in which 20 patients who were chronically consuming opioids were compared with 20 matched controls. Patients completed the Sexual Desire Inventory (SDI), the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Chronic Illness Therapy with general and fatigue subscales (FACT-G/FACIT-F), and the Edmonton Symptom Assessment System (ESAS) questionnaires. Serum samples were collected for testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). RESULTS Comparing the opioid group with the control group, 18 of the 20 patients (90%; 95% confidence interval [CI], 65,98%) exhibited hypogonadism, compared with 8 of the 20 control patients (40%; 95% CI, 19,64%). The median testosterone level was 145 ng/dL versus 399.5 ng/dL (5.0 nmol/L vs. 13.9 nmol/L; P < 0.0001), the median FSH level was 2.85 milli,International Units (mIU)/mL versus 5.3 mIU/mL (P = 0.08), the median LH level was 1.8 mIU/mL versus 4.2 mIU/mL (P = 0.0014), the median SDI-dyadic score was 18.5 versus 40 (P = 0.01), the median SDI-solitary score was 0 versus 5 (P = 0.007), the HADS (anxiety) score was 8.5 versus 5.5 (P = 0.053), the HADS (depression) score was 7.5 versus 1.5 (P = 0.0002), the FACT-G score was 64 versus 96.3 (P = 0.0001), and the FACIT-F score was 24 versus 46 (P = 0.0003). CONCLUSIONS Survivors of cancer who chronically consumed opioids experienced symptomatic hypogonadism with significantly higher levels of depression, fatigue, and sexual dysfunction. With the increasing use of opioids among patients with cancer, further research in improving quality-of-life outcomes is warranted. Cancer 2004;100:851,8. © 2004 American Cancer Society. [source] Treating cancer with PEG IntronCANCER, Issue 2 2002Pharmacokinetic profile, dosing guidelines for an improved interferon-alpha-2b formulation Abstract BACKGROUND PEG Intron (pegylated interferon-alpha-2b [IFN-,-2b]; Schering-Plough, Kenilworth, NJ) has demonstrated delayed clearance and increased area under the curve compared with native IFN-,-2b. Studies in patients with chronic hepatitis C infection and malignancies have demonstrated both biologic and clinical activity of PEG Intron and have provided empiric data to compare the pharmacokinetics (PK) and pharmacodynamics of PEG Intron and IFN-,-2b. METHODS The authors conducted a review of the available data comparing the PK and pharmacodynamic effects of PEG Intron and IFN-,-2b. Safety and efficacy data from Phase I/II studies of PEG Intron in patients with chronic myelogenous leukemia (CML) and solid tumors were also reviewed. RESULTS Data from patients with chronic hepatitis C infection suggest that exposure to IFN at a PEG Intron dose of 0.25 ,g/kg per week is similar to that observed after administration of IFN-,-2b at a dose of 3 million International Units, three times per week. PEG Intron at doses up to 6 ,g/kg per week was well tolerated and demonstrated clinical activity in patients with CML and solid tumors, including metastatic melanoma and renal cell carcinoma. CONCLUSIONS Dose intensification can be achieved safely in patients with CML and solid tumors using PEG Intron, which could improve efficacy. These results provide useful dosing guidelines to clinicians investigating the antitumor activity of PEG Intron in patients with malignancies. More data are needed to determine the optimal dose in various oncologic indications. However, these results provide a sound rationale for further investigation of PEG Intron. Cancer 2002;95:389,96. © 2002 American Cancer Society. DOI 10.1002/cncr.10663 [source] Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis C virus infection for the fiscal year 2008 in JapanHEPATOLOGY RESEARCH, Issue 1 2010Hiromitsu Kumada In the 2008 guidelines for the treatment of patients with chronic hepatitis C, pegylated interferon (Peg-IFN) combined with ribavirin for 48 weeks are indicated for treatment-naive patients infected with hepatitis C virus (HCV) of genotype 1. Treatment is continued for an additional 24 weeks (72 weeks total) in the patients who have remained positive for HCV RNA detectable by the real-time polymerase chain reaction at 12 weeks after the start of treatment, but who turn negative for HCV RNA during 13,36 weeks on treatment. Re-treatment is aimed to either eradicate HCV or normalize transaminase levels for preventing the development of hepatocellular carcinoma (HCC). For patients with compensated cirrhosis, the clearance of HCV RNA is aimed toward improving histological damages and decreasing the development of HCC. The recommended therapeutic regimen is the initial daily dose of 6 million international units (MIU) IFN continued for 2,8 weeks that is extended to longer than 48 weeks, if possible. IFN dose is reduced to 3 MIU daily in patients who fail to clear HCV RNA by 12 weeks for preventing the development of HCC. Splenectomy or embolization of the splenic artery is recommended to patients with platelet counts of less than 50 × 103/mm3 prior to the commencement of IFN treatment. When the prevention of HCC is at issue, not only IFN, but also liver supportive therapy such as stronger neo-minophagen C, ursodeoxycholic acid, phlebotomy, branched chain amino acids (BCAA), either alone or in combination, are given. In patients with decompensated cirrhosis, by contrast, reversal to compensation is attempted. [source] Establishment of the 1st World Health Organization international standards for human papillomavirus type 16 DNA and type 18 DNAINTERNATIONAL JOURNAL OF CANCER, Issue 12 2010Dianna E. Wilkinson Abstract A World Health Organization collaborative study was conducted to evaluate candidate international standards for human papillomavirus (HPV) Type 16 DNA (NIBSC code 06/202) and HPV Type 18 DNA (NIBSC code 06/206) for use in the amplification and detection steps of nucleic acid-based assays. The freeze-dried candidate international standards were prepared from bulk preparations of cloned plasmid containing full-length HPV-16 or HPV-18 genomic DNA. Nineteen laboratories from 13 countries participated in the study using a variety of commercial and in-house quantitative and qualitative assays. The data presented here indicate that, upon freeze-drying, there is no significant loss in potency for the candidate HPV-18 DNA and a slight loss in potency for the candidate HPV-16 DNA; although this is likely not scientifically relevant when assay precision is considered. In general, the individual laboratory mean estimates for each study sample were grouped ±,2 log10 around the theoretical HPV DNA concentration of the reconstituted ampoule (1 × 107 HPV genome equivalents/mL). The agreement between laboratories is improved when potencies are made relative to the candidate international standards, demonstrating their utility in harmonizing amplification and detection steps of HPV-16 and ,18 DNA assays. Degradation studies indicate that the candidate international standards are extremely stable and suitable for long-term use. Based on these findings, the candidate standards were established as the 1st WHO international standards for HPV-16 DNA and HPV-18 DNA, each with a potency of 5 × 106 international units (IU) per ampoule or 1 × 107 IU mL,1 when reconstituted as directed. [source] Development of real-time detection direct test for hepatitis B virus and comparison with two commercial tests using the WHO international standardJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2003MOTOKAZU MUKAIDE Abstract Aims:, A highly reproducible and sensitive hepatitis B virus real-time detection direct (HBV RTD-direct) test using DNA extraction by magnetic beads coated with polyclonal anti-HBsAg, followed by the real-time detection polymerase chain reaction (PCR) method, was developed for the detection of HBV DNA. Methods:, The HBV DNA could be extracted from the HBsAg positive viral particles without resulting in viral DNA fragmentation. The HBV RTD-direct test was validated using a serial dilution panel of the WHO standard HBV DNA 97/746 I. Results:, The test had a dynamic range of 0.7,8.0 log10 international units (IU) per mL and the results were shown to be comparable to those obtained with two commercially available tests: the HBV DNA transcription-mediated amplification-hybridization protection assay and the Amplicor HBV Monitor test. In addition, the HBV RTD-direct test, based on magnetic extraction, successfully eliminated PCR inhibitors in clinical specimens. Conclusion:, We conclude that the HBV RTD-direct test is an excellent alternative for monitoring patients undergoing antiviral treatment or for screening various clinical specimens. [source] High response rate after intratumoral treatment with interleukin-2CANCER, Issue 17 2010Results from a phase 2 study in 51 patients with metastasized melanoma Abstract BACKGROUND: Systemic high-dose interleukin-2 (IL-2) achieved long-term survival in a subset of patients with advanced melanoma. The authors reported previously that intratumorally applied IL-2 induced complete local responses of all metastases in >60% of patients. The objectives of the current study were to confirm those results in a larger cohort and to identify patient or regimen characteristics associated with response. METHODS: Patients with melanoma who had a median of 12 injectable metastases received intratumoral IL-2 treatments 3 times weekly until they achieved clinical remission. The initial dose of 3 million international units was escalated, depending on the individual patient's tolerance. RESULTS: Forty-eight of 51 patients were evaluable. Only grade 1/2 toxicity was recorded. A complete response that lasted ,6 months was documented in 70% of all injected metastases. A complete local response of all treated metastases was achieved in 33 patients (69%), including 11 patients who had between 20 and 100 metastases. Response rates were higher for patients who had stage III disease compared with patients who had stage IV disease. No objective responses of distant untreated metastases were observed. The 2-year survival rate was 77% for patients with stage IIIB/IIIC disease and 53% for patients with stage IV disease. Efficacy and survival did not differ between patients who had ,20 lesions and patients who had <20 lesions. CONCLUSIONS: Intratumoral IL-2 treatment elicited complete local responses in a high percentage of patients. Further studies will be required to investigate the mode of action of this treatment and its impact on survival. Cancer 2010. © 2010 American Cancer Society. [source] Phase II study of alpha-tocopherol in improving the cognitive function of patients with temporal lobe radionecrosisCANCER, Issue 2 2004Agnes S. Chan Ph.D. Abstract BACKGROUND Radiotherapy is an important treatment modality for brain tumors and is the standard radical treatment for nasopharyngeal carcinoma (NPC). However, the treatment is not free of side effects, and one possible neurologic sequela is the occurrence of temporal lobe radionecrosis (TLN) associated with cognitive dysfunction. Currently, there is no effective intervention to improve patients' cognitive performance. METHODS Twenty-nine patients with TLN after radiotherapy for NPC were recruited on a voluntary basis. Among them, 19 patients (15 males and 4 females) received a megadose of alpha-tocopherol (vitamin E) (2000 international units per day) for 1 year, whereas the other 10 (5 males and 5 females) served as control patients. Their cognitive function (i.e., global cognitive ability, attention, memory, language, and executive function) was evaluated by a battery of neuropsychological tests before and after treatment. RESULTS Significant improvement in global cognitive ability (P = 0.035) and memory (verbal: P = 0.036; visual: P = 0.007) occurred among patients in the treatment group after a 1-year medication period. In addition, the executive function of the treatment group improved significantly (P = 0.04). No difference was found between the two groups with respect to attention or language. CONCLUSIONS The current investigation was a preliminary study on the effect of alpha-tocopherol on the cognitive function of patients with TLN after radiotherapy for NPC. In view of the absence of effective treatment for patients with cerebral radionecrosis, alpha-tocopherol has the potential to be a complementary intervention for patients with cognitive dysfunction due to TLN. Cancer 2004;100:398,404. © 2003 American Cancer Society. [source] Combined intraarterial 5-fluorouracil and subcutaneous interferon-, therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branchesCANCER, Issue 2 2002Masato Sakon M.D. Abstract BACKGROUND The prognosis of hepatocellular carcinoma (HCC) invading into the major branches of the portal vein (Vp3) is extremely poor. METHODS Eleven consecutive patients with HCC and Vp3 were treated with 2,6 cycles of a "basic" combination therapy consisting of continuous arterial infusion of 5-fluorouracil (450,500 mg/day, for the initial 2 weeks) and subcutaneous injection of interferon-, (5 million international units, 3 times/week, 4 weeks). In the first 3 patients, methotrexate (90 mg/day 1 of every week), cisplatin (10 mg/day), and leucovorin (30 mg/days 2 and 3 of every week) also were administered for the initial 2 weeks ("full" regimen). RESULTS In 8 (73%) of 11 patients, an objective response (complete response [CR] or partial response [PR]) was observed with marked regression of tumor and decrease in tumor markers. The use of the full regimen was associated with objective response in all patients; instead, they developed thrombocytopenia or leukopenia. In the subsequent 8 patients with basic regimen, 5 patients showed CR (2 cases) or PR (3 cases; objective response rate, 63%), and leukopenia was observed only in 1 patient. CONCLUSIONS Simple combination therapy with subcutaneous interferon-, and intraarterial 5-fluorouracil therefore is a promising treatment modality for intractable HCC with Vp3. Cancer 2002;94:435,42. © 2002 American Cancer Society. [source] | ||||||||||