1.
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.
2.
Arsenic trioxide combined with transarterial chemoembolization for primary liver cancer: A meta-analysis.
Lv, XH, Wang, CH, Xie, Y
Journal of gastroenterology and hepatology. 2017;(9):1540-1547
Abstract
BACKGROUND AND AIM The benefit of combination therapy of arsenic trioxide (As2 O3 ) and transarterial chemoembolization (TACE) is debated. This meta-analysis was conducted to determine whether As2 O3 &TACE therapy achieves better therapeutic effects compared with TACE alone for primary liver cancer. METHODS A systematic search of both English and Chinese databases was conducted for randomized controlled trials. The main outcomes were therapeutic responses, survival rates, improvement in quality of life, and adverse events. All data analyses in this study were carried out using Review Manager software and STATA software. RESULTS Eighteen randomized controlled trials involving 1412 participants were included. The pooled objective response rate was significantly higher in the As2 O3 &TACE group compared with the TACE group (relative risk [RR] 1.36, 95% confidence interval [CI] 1.16-1.58, P < 0.0001), and the pooled clinical benefit rate was also significantly higher (RR 1.18, 95% CI 1.08-1.29, P = 0.0002). A higher pooled result was obtained from the combination group for 1-year survival rate (RR 1.37, 95% CI 1.23-1.53, P < 0.00001). As2 O3 &TACE therapy was not superior to TACE alone for improvement in quality of life (RR 1.15, 95% CI 0.98-1.36, P = 0.09). There was no significant difference in the risk of adverse effects. When a subgroup analysis was performed, both administration methods of As2 O3 (intravenous or arterial) were effective for all evaluating indicators except the improvement in quality of life. CONCLUSIONS Adjuvant As2 O3 therapy combined with TACE achieves better therapeutic effects compared with TACE alone. Both the intravenous administration of As2 O3 and the arterial administration of As2 O3 were good options for clinical practice.
3.
All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.
Ma, Y, Liu, L, Jin, J, Lou, Y
PloS one. 2016;(7):e0158760
Abstract
BACKGROUND Recently, the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL), but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL. METHODS We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity. RESULTS Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009), overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009), complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03). There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07). CONCLUSION Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.