0
selected
-
1.
Interferon alpha therapy in essential thrombocythemia and polycythemia vera-a systematic review and meta-analysis.
Bewersdorf, JP, Giri, S, Wang, R, Podoltsev, N, Williams, RT, Tallman, MS, Rampal, RK, Zeidan, AM, Stahl, M
Leukemia. 2021;(6):1643-1660
-
-
Free full text
-
Abstract
Data on the efficacy and safety of interferon (IFN)-α for the treatment of essential thrombocythemia (ET) and polycythemia vera (PV) are inconsistent. We conducted a systematic review and meta-analysis and searched MEDLINE and EMBASE via Ovid, Scopus, COCHRANE registry of clinical trials, and Web of Science from inception through 03/2019 for studies of pegylated IFN (peg-IFN) and non-pegylated IFN (non-peg-IFN) in PV and ET patients. Random-effects models were used to pool response rates for the primary outcome of overall response rate (ORR) defined as a composite of complete response, partial response, complete hematologic response (CHR) and partial hematologic response. Peg-IFN and non-peg-IFN were compared by meta-regression analyses. In total, 44 studies with 1359 patients (730 ET, 629 PV) were included. ORR were 80.6% (95% confidence interval: 76.6-84.1%, CHR: 59.0% [51.5%-66.1%]) and 76.7% (67.4-84.0%; CHR: 48.5% [37.8-59.4%]) for ET and PV patients, respectively. In meta-regression analyses results did not differ significantly for non-peg-IFN vs. peg-IFN. Annualized rates of thromboembolic complications and treatment discontinuation due to adverse events were low at 1.2% and 8.8% for ET and 0.5% and 6.5% for PV patients, respectively. Both peg-IFN and non-peg-IFN can be effective and safe long-term treatments for ET and PV.
-
2.
Overview of Targeted Therapies for Adult T-Cell Leukemia/Lymphoma.
Nasr, R, Marçais, A, Hermine, O, Bazarbachi, A
Methods in molecular biology (Clifton, N.J.). 2017;:197-216
Abstract
Adult T-Cell Leukemia/lymphoma (ATL) is the first human malignancy associated with a chronic infection by a retrovirus, the human T-cell lymphotropic virus type I (HTLV-I). ATL occurs, after a long latency period, only in about 5% of 10-20 millions infected individuals. ATL has a dismal prognosis with a median survival of less than 1 year, mainly due to its resistance to chemotherapy and to a profound immunosuppression. The viral oncoprotein, Tax, plays a major role in ATL oncogenic transformation by interfering with cell proliferation, cell cycle, apoptosis, and DNA repair. The diversity in ATL clinical features and prognosis led to Shimoyama classification of ATL into four clinical subtypes (acute, lymphoma, chronic, and smoldering) requiring different therapeutic strategies. Clinical trials, mainly conducted in Japan, demonstrated that combination of chemotherapy could induce acceptable response rate in the lymphoma subtype but not in acute ATL. However, long-term prognosis remains poor for both subtypes, due to a high relapse rate. Similarly, whether managed by a watchful waiting or treated with chemotherapy, the indolent forms (smoldering and chronic) have a poor long-term outcome. An international meta-analysis showed improved survival in the leukemic subtypes of ATL (chronic, smoldering as well as a subset of the acute subtype) with the use of two antiviral agents, zidovudine and interferon-alpha, and accordingly, this combination should be considered the standard first-line treatment in this context. ATL patients with lymphoma subtype benefit from induction chemotherapy, given simultaneously or sequentially with an antiviral combination of zidovudine and interferon-alpha. Allogeneic hematopoietic stem cells transplantation remains a promising and potentially curative approach but is limited to a small number of patients. Novel drugs such as arsenic trioxide in combination with interferon-alpha or monoclonal antibodies such as anti-CXCR4 have shown promising results and warrant further investigation.
-
3.
Extended peginterferon plus ribavirin treatment for 72 weeks versus standard peginterferon plus ribavirin treatment for 48 weeks in chronic hepatitis C genotype 1 infected slow-responder adult patients.
Katz, LH, Goldvaser, H, Gafter-Gvili, A, Tur-Kaspa, R
The Cochrane database of systematic reviews. 2012;(9):CD008516
Abstract
BACKGROUND The standard length of peginterferon plus ribavirin treatment for chronic hepatitis C virus (HCV) genotype 1 infected patients is 48 weeks. However, the number of patients demonstrating a sustained virological response is not high. In order to improve sustained virological response, extending the length of the treatment period has been suggested. OBJECTIVES To study the benefits and harms of extended 72-week treatment in comparison with 48-week treatment with peginterferon plus ribavirin in patients with chronic HCV genotype 1 infection who have shown a slow antiviral response. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS until November 2011. We identified further trials by reviewing reference lists and contacting principal authors. SELECTION CRITERIA Trials were eligible for this review if they included patients infected with hepatitis C virus genotype 1 who had a slow antiviral response, and if those patients were randomised to completing 72 weeks versus 48 weeks of treatment with pegylated interferon and ribavirin. DATA COLLECTION AND ANALYSIS Two authors independently assessed the trials for risk of bias, and extracted the data. The primary outcomes were overall mortality, liver-related mortality, and liver-related morbidity. We extracted data separately according to two definitions of slow responders: 1) patients with ≥ 2 log viral reduction but still detectable HCV RNA after 12 weeks of treatment and undetectable HCV RNA after 24 weeks of treatment; 2) patients with detectable HCV RNA after four weeks of treatment. We calculated risk ratios from individual trials as well as in the meta-analyses of trials. MAIN RESULTS We included seven trials with 1369 participants. All trials had high risk of bias. Five trials used our first definition of slow responders, and three other trials (including one that used both definitions) used the second definition. None of the included trials mentioned our primary outcomes. However, regarding the secondary outcomes, extension of the treatment period to 72 weeks increased the sustained virological response according to both definitions (71/217 (32.7%) versus 52/194 (26.8%); risk ratio (RR) 1.43, 95% confidence interval (CI) 1.07 to 1.92, P = 0.02, I(2) = 8%; and 265/499 (53.1%) versus 207/496 (41.7%); RR 1.27, 95% CI 1.07 to 1.50, P = 0.006, I(2) = 38%), with a risk difference of 0.11 and calculated number needed to treat of nine. The end of treatment response was not significantly different between the two treatment groups. The number of participants who relapsed virologically was found to be lower in the groups that had been treated for 72 weeks using both definitions (27/84 (32.1%) versus 46/91 (50.5%); RR 0.59, 95% CI 0.40 to 0.86, P = 0.007, I(2) = 18%, 3 trials; and 85/350 (24.3%) versus 146/353 (41.4%); RR 0.59, 95% CI 0.47, 0.73, P < 0.000001, I(2) = 0%, 3 trials). The length of treatment did not significantly affect the adherence (247/279 (88.5%) versus 252/274 (92.0%); RR 0.95, 95% CI 0.84 to 1.07, P = 0.42, I(2) = 69%, 3 trials). In the single trial that reported adverse events, no significant difference was seen between the two treatment groups. AUTHORS' CONCLUSIONS This review demonstrates higher a proportion of sustained virological response after extension of treatment from 48 weeks to 72 weeks in HCV genotype 1 infected patients in whom HCV RNA was still detectable but decreased by ≥ 2 log after 12 weeks and became negative after 24 weeks of treatment, and in patients with detectable HCV RNA after four weeks of treatment with peginterferon plus ribavirin. The observed intervention effects can be caused by both systematic error (bias) and random errors (play of chance). There was no reporting on mortality and the reporting of clinical outcomes and adverse events was insufficient. More data are needed in order to recommend or reject the policy of extending the treatment period for slow responders.
-
4.
Chinese herbal medicine and interferon in the treatment of chronic hepatitis B: a meta-analysis of randomized, controlled trials.
McCulloch, M, Broffman, M, Gao, J, Colford, JM
American journal of public health. 2002;(10):1619-28
-
-
Free full text
-
Abstract
OBJECTIVES This meta-analysis was conducted to examine the effectiveness of Chinese herbal medicine (either alone or with interferon alfa) in treating chronic hepatitis B. METHODS We searched the TCMLARS, AMED, CISCOM, EMBASE, MEDLINE, and Cochrane Collaboration databases and then hand-searched the articles' bibliographies. RESULTS Chinese herbal medicine significantly increased seroreversion of HBsAg and was equivalent to interferon alfa in seroreversion of HBeAg and hepatitis B virus (HBV) DNA; Chinese herbal medicine combined with interferon alfa significantly increased seroreversion of HBsAg, HBeAg, and HBV DNA. The Chinese herbal medicine active component bufotoxin combined with interferon alfa significantly increased HBeAg and HBV DNA seroreversion. The Chinese herbal medicine active component kurorinone was equivalent to interferon alfa in seroreversion of HBeAg and HBV DNA. CONCLUSIONS Although the quality of existing studies was poor, these data suggest that further trials of Chinese Herbal Medicine and interferon in chronic hepatitis B infection are justified.
-
5.
Alpha-interferon does not increase the efficacy of 5-fluorouracil in advanced colorectal cancer.
Thirion, P, Piedbois, P, Buyse, M, O'Dwyer, PJ, Cunningham, D, Man, A, Greco, FA, Colucci, G, Köhne, CH, Di Constanzo, F, et al
British journal of cancer. 2001;(5):611-20
-
-
Free full text
-
Abstract
Two meta-analyses were conducted to quantify the benefit of combining alpha-IFN to 5FU in advanced colorectal cancer in terms of tumour response and survival. Analyses were based on a total of 3254 individual patient data provided by principal investigators of each trial. The meta-analysis of 5FU +/- LV vs. 5FU +/- LV + alpha-IFN combined 12 trials and 1766 patients. The meta-analysis failed to show any statistically significant difference between the two treatment groups in terms of tumour response or survival. Overall tumour response rates were 25% for patients receiving no alpha-IFN vs. 24% for patients receiving alpha-IFN (relative risk, RR = 1.02), and median survivals were 11.4 months for patients receiving no alpha-IFN vs. 11.5 months for patients receiving alpha-IFN (hazard ratio, HR = 0.95). The meta-analysis of 5FU + LV vs. 5FU + alpha-IFN combined 7 trials, and 1488 patients. This meta-analysis showed an advantage for 5FU + LV over 5FU + alpha-IFN which was statistically significant in terms of tumour response (23% vs. 18%; RR = 1.26;P = 0.042), and of a borderline significance for overall survival (HR = 1.11;P = 0.066). Metastases confined to the liver and primary rectal tumours were independent favourable prognostic factors for tumour response, whereas good performance status, metastases confined to the liver or confined to the lung, and primary tumour in the rectum were independent favourable prognostic factors for survival. We conclude that alpha-IFN does not increase the efficacy of 5FU or of 5FU + LV, and that 5FU + alpha-IFN is significantly inferior to 5FU + LV, for patients with advanced colorectal cancer.