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OncoTargets and Therapy 2014Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal... (Review)
Review
Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. Although some newly approved drugs (thalidomide, lenalidomide, and bortezomib) demonstrate significant benefit for MM patients with improved survival, all MM patients still relapse. Arsenic trioxide (ATO) is the most active single agent in acute promyelocytic leukemia, the antitumor activity of which is partly dependent on the production of reactive oxygen species. Due to its multifaceted effects observed on MM cell lines and primary myeloma cells, Phase I/II trials have been conducted in heavily pretreated patients with relapsed or refractory MM. Therapy regimens varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with other agents available for the treatment of MM. Although ATO-based combination treatment was well tolerated by most patients, most trials found that ATO has limited effects on MM patients. However, since small numbers of patients were randomized to different treatment arms, trials have not been statistically powered to determine the differences in progression-free survival and overall survival among the experimental arms. Therefore, large Phase III studies of ATO-based randomized controlled trials will be needed to establish whether ATO has any potential beneficial effects in the clinical setting.
PubMed: 25246802
DOI: 10.2147/OTT.S67165 -
Hematology (Amsterdam, Netherlands) Dec 2023Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Arsenic trioxide (ATO) might be effective for myelodysplastic syndrome (MDS) by apoptosis induction and demethylation. But ATO has not been widely recommended for small sample and conflicting conclusion of existing trials. This review aimed to systematically evaluate the efficacy of regimens containing ATO for the MDS and explore optimal combination.
METHOD
Randomized clinical trials (RCTs) about ATO regimens were retrieved from China National Knowledge Infrastructure, Embase and PubMed. With odds ratio (OR) as the effect size, network meta-analysis (NMA) and component network meta-analysis (CNMA) were conducted by R and 'netmeta' package, after study selection, quality assessment and data extraction.
RESULT
Thirty-night RCTs were included with a total of 2125 patients, including 1235 treated by ATO containing regimen. With support therapy alone as reference, no inconsistency and heterogeneity were observed. Although NMA did not demonstrate better efficacy of ATO alone, the result of CNMA indicated that ATO was effective in the improvement of overall remission (ORR) [OR = 2.09(1.61, 2.71)] and complete remission (CR) [OR = 1.66(1.25, 2.21)]. Five ATO-containing regimens reported could effectively improve ORR, some of them benefit in CR or hematological improvement (HI) as well. ATO + Traditional Chinese Medicine (TCM), ATO + Thalidomide (T)+TCM, ATO + Chemotherapy (Chem)+T + TCM were regarded as the optimal combination, which improved both ORR, CR and HI in theory. ATO did not increase the risk of common adverse events compared to supportive therapy [(OR = 0.90(0.67, 1.21)].
CONCLUSION
ATO may be an effective and well-tolerant option for patients with myelodysplastic syndrome.
Topics: Humans; Arsenic Trioxide; Network Meta-Analysis; Arsenicals; Oxides; Myelodysplastic Syndromes; Treatment Outcome
PubMed: 37908176
DOI: 10.1080/16078454.2023.2274149 -
Medicine May 2018Primary hepatic carcinoma (PHC) is the third commonest leading to cancer death around the world, and transarterial chemoembolization (TACE) has been proposed as the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Primary hepatic carcinoma (PHC) is the third commonest leading to cancer death around the world, and transarterial chemoembolization (TACE) has been proposed as the first-line therapeutic treatment for patients with unresectable PHC. This study aims to determine whether the combination of As2O3 and TACE is superior to alone TACE for achieving more clinical therapeutic efficacy, survival time, life quality and safety in patients with unresectable PHC.
METHODS
A comprehensive literature search was conducted on the clinical controlled trials comparing therapeutic effects of As2O3 & TACE versus alone TACE for unresectable PHC through English databases (including PubMed, Embase, and the Cochrane Library) and Chinese databases (including China Knowledge Resource Integrated Database, Wanfang Database, Weipu Database, and Chinese Biomedical Database). The last search was in 30 August 2017. A recursive search was performed with bibliographies of relevant studies. There were no language restrictions. Primary outcomes, defined a priori, were therapeutic responses (clinical effective rate and clinical benefit rate), survival time, life quality, and adverse events of As2O3 & TACE compared with alone TACE expressed as relative risk (RR) with 95% confidence intervals (CI).
RESULTS
25 clinical controlled trials involving 1886 participants were included. We found that there were significant superiority associated with As2O3 & TACE compared with alone TACE in clinical benefit rate (RR: 1.24, 95% CI: 1.12-1.37), clinical effective rate (RR: 1.35, 95% CI: 1.17-1.55), 2-year survival rate (RR: 1.45, 95% CI: 1.20-1.75), and improving of KPS (RR: 1.31, 95% CI: 1.14-1.50). These associations were also observed in subgroups by intervened methods of As2O3 and pulmonary metastasis. Notably, the pooled relative risk of retention of sodium and water was obviously raised in patients with As2O3 & TACE therapy (RR: 16.616, 95% CI: 8.01 - 34.486).
CONCLUSION
The superiority of adjuvant As2O3 therapy combined with TACE in PHC individuals will outweigh alone TACE therapy, especially in PHC populations with pulmonary metastasis.
Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Combined Modality Therapy; Humans; Liver Neoplasms; Oxides; Quality of Life; Survival Rate; Treatment Outcome
PubMed: 29718867
DOI: 10.1097/MD.0000000000010613 -
Cancer Treatment Reviews Aug 2009Arsenic trioxide (ATO) has been proposed as an option for the treatment of relapsing or refractory multiple myeloma. In order to critically appraise the published... (Review)
Review
Arsenic trioxide (ATO) has been proposed as an option for the treatment of relapsing or refractory multiple myeloma. In order to critically appraise the published clinical evidence, a systematic search of the databases PubMed, Embase, Web of Science and the Cochrane Library was performed. Studies were selected according to prospectively defined criteria. Eventually 16 articles met the inclusion criteria. Six trials evaluated ATO as a single agent or in combination with ascorbic acid and ten trials added ATO to other cytostatic agents. Apart from one randomized controlled trial (RCT), all other studies were designed as case series. The patient numbers were generally small, treatment regimens differed both regarding the dosage of ATO and combinations with other drugs. Monotherapy with ATO resulted in partial response rates between 0% and 17% and minimal responses of 7-33%, resulting in mean overall response rates of 30%. Overall response rates in combined regimens varied widely between 12% and 100%. Response rates for patients in the three arms of the RCT did not differ significantly. The results demonstrate the potential efficacy of ATO in refractory multiple myeloma, but the validity of these findings is reduced by considerable methodological flaws. RCTs should further investigate the efficacy of ATO or new arsenicals in order to overcome methodological concerns of the studies presented here. With respect to the higher evidence level of new substances such as bortezomib or lenalidomide, at present ATO has no role in routine management of relapsed or refractory myeloma.
Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Clinical Trials as Topic; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Oxides; Treatment Outcome
PubMed: 19464807
DOI: 10.1016/j.ctrv.2009.04.007 -
Zhong Xi Yi Jie He Xue Bao = Journal of... Sep 2009To systematically review the efficacy and safety of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review the efficacy and safety of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL).
METHODS
The Cochrane Library (Issue 1, 2009), Cochrane Central Register of Controlled Trials (from 1970 to January 2009), MEDLINE (from 1978 to October 2008), EMBASE (from 1950 to March 2009), Chinese Biological Medical Literature Database (from 1978 to December 2008), China National Knowledge Infrastructure (CNKI, from 1994 to December 2008), and China Medical Academic Conference Database (from 1994 to December 2008) were electronically searched. We also searched the Meta-Register of controlled trials, Conference Proceedings of American Society of Hematology (from 1946 to December 2008) and Conference Proceedings of American Society of Clinical Oncology (from 1946 to December 2008) on the internet for grey literature. The related journals in the library of Third Military Medical University were hand-searched. The randomized controlled trials (RCTs) of ATO in treatment of APL were included. We adopted complete remission, overall survival rate, disease free survival rate, time to complete remission, relapse rate, mortality and adverse reactions as outcome indicators. Data were entered and analyzed with the Cochrane review manager software 5.0 (RevMan 5.0).
RESULTS
After merger of the included trials, five eligible RCTs with 328 cases were included. All the RCTs focused on the comparison of all-trans retinoic acid (ATRA) plus ATO regimen with ATRA monotherapy. Meta-analysis showed that the effect indexes for time to complete remission, two-year disease free survival rate, relapse rate, incidence of edema and incidence rate of QT interval prolongation were -1.20 [-1.68, -0.72], 8.64 [1.66,45.00], 0.21 [0.09,0.47], 4.16 [1.46,11.79] and 22.10 [2.75,177.49], respectively. The influences on other outcome indicators such as complete remission and leukocytosis were statistically non-significant.
CONCLUSION
ATO can prolong disease free survival and reduce the time to complete remission and relapse rate of newly diagnosed APL patients, and increase the incidence of edema and prolongation of corrected QT interval during the treatment. Due to limitation of the included trials, this conclusion needs to be validated by further studies.
Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Humans; Leukemia, Promyelocytic, Acute; Oxides
PubMed: 19747432
DOI: 10.3736/jcim20090901 -
International Journal of... Apr 2020Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). APL is famed with some special blood coagulation disorders such as disseminated... (Review)
Review
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). APL is famed with some special blood coagulation disorders such as disseminated intravascular coagulation (DIC). The therapeutic methods of APL contain All Trans Retinoic Acid (ATRA), arsenic trioxide (ATO) or/and chemotherapy. Many studies have been done on APL blood disorders and its treatment. These studies have shown different results. In this systematic article, we tried to review the effect of ATO therapy with or without ATRA and chemotherapy on DIC parameters (D-dimer, Prothrombin Time, Activated Partial Thrombin Time, Platelet count) in APL patients. The result of included studies demonstrated that although ATO can reduce the number of malignant cells in the bone marrow and peripheral blood, it does not have enough potential to attenuate the danger of high score DIC that is usual in APL patients and should be better to be used with other therapeutic methods.
PubMed: 32461798
DOI: No ID Found -
Zhong Xi Yi Jie He Xue Bao = Journal of... Nov 2009The studies have demonstrated that arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) takes effects in treatment of acute promyelocytic leukemia... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The studies have demonstrated that arsenic trioxide (ATO) in combination with all-trans retinoic acid (ATRA) takes effects in treatment of acute promyelocytic leukemia (APL) through different underlying mechanisms. This has established the molecular foundation of ATO plus ATRA therapy. Currently, ATO plus ATRA has also been widely used in clinical practice.
OBJECTIVE
To assess the efficacy and safety of ATO in combination with ATRA for APL.
SEARCH STRATEGY
The Cochrane Library (Issue 1, 2009), Cochrane Central Register of Controlled Trials (from 1970 to January 2009), MEDLINE (from 1978 to October 2008), EMBASE (from 1950 to March 2009), Chinese Biological Medical Literature Database (from 1978 to December 2008), CNKI (from 1994 to December 2008), China Medical Academic Conference Database (from 1994 to December 2008) were electronically searched. We also searched the Meta-Register of Controlled Trials, Conference Proceedings of American Society of Hematology (from 1946 to December 2008) and Conference Proceedings of American Society of Clinical Oncology (from 1946 to December 2008) on the internet for grey literature. The authors also hand-searched Chinese periodicals potentially related to the question including Chinese Journal of Hematology, Journal of Experimental Hematology and Journal of Clinical Hematology.
INCLUSION CRITERIA
All randomized controlled trials comparing ATO plus ATRA with other regimens for the treatment of APL were included. Intervention and comparison regimens include: 1) ATO plus ATRA vs ATO monotherapy; 2) ATO plus ATRA vs ATRA monotherapy; 3) ATO plus ATRA vs ATRA plus chemotherapy; 4) ATO plus ATRA vs ATO+ATRA+chemotherapy.
DATA EXTRACTION AND ANALYSIS
Related data concerning complete remission rate, overall survival rate, and disease free survival rate, time to complete remission, relapse rate, mortality and adverse reactions were extracted independently by two reviewers. The different statistical methods were applied according to different data type with RevMan 5.0 software.
RESULTS
After merging of the included trials, seven eligible randomized controlled trials with 392 cases were analyzed, among which 6 RCTs were methodologically graded as middle and one as of high risk of bias. The control therapies included ATO monotherapy, ATRA monotherapy and chemotherapy with ATO plus ATRA. Compared with ATO monotherapy, ATO plus ATRA could improve time to complete remission and relapse rate of newly diagnosed APL, but could not improve the complete remission rate, disease free survival rate, mortality and liver dysfunction of relapsed APL patients based on meta-analysis and sensitivity analysis. Compared with ATRA monotherapy, ATO plus ATRA shortened the time to complete remission, improved the disease free survival rate and relapse rate, but increased the incidence of edema during the treatment. Compared with chemotherapy with ATO plus ATRA, ATO plus ATRA could improve the complete remission rate, relapse rate, mortality and adverse reactions.
CONCLUSION
For newly diagnosed APL, ATO plus ATRA is superior to ATO monotherapy, ATRA monotherapy and chemotherapy with ATO plus ATRA, but due to the lack of data about comparison with the current standard treatment regimen (ATRA plus chemotherapy), it is not enough to recommend ATO plus ATRA as a frontline therapy. For relapsed APL, ATO plus ATRA is not superior to ATO monotherapy, and ATRA plus ATO is not a supportive therapy. Due to limitation of sample size and risk of bias from the included trials, the effects of ATO plus ATRA need to be confirmed by large and high-quality randomized controlled trials.
Topics: Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Humans; Leukemia, Promyelocytic, Acute; Oxides; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome; Tretinoin
PubMed: 19912733
DOI: 10.3736/jcim20091102 -
Cancers May 2020It has been suggested that 1-2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with... (Review)
Review
It has been suggested that 1-2% of acute promyelocytic leukemia (APL) patients present variant rearrangements of retinoic acid receptor alpha (RARα) fusion gene, with the promyelocytic leukaemia zinc finger (PLZF)/RAR being the most frequent. Resistance to all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested in PLZF/RAR and other variant APLs. Herein, we analyze the incidence, characteristics, and outcomes of variant APLs reported to the multinational PETHEMA (Programa para el Tratamiento de Hemopatias Malignas) registry, and we perform a systematic review in order to shed light on strategies to improve management of these extremely rare diseases. Of 2895 patients with genetically confirmed APL in the PETHEMA registry, 11 had variant APL (0.4%) (9 PLZF-RAR and 2 NPM1-RAR), 9 were men, with median age of 44.6 years (3 months to 76 years), median leucocytes (WBC) 16.8 × 10/L, and frequent coagulopathy. Eight patients were treated with ATRA plus chemotherapy-based regimens, and 3 with chemotherapy-based. As compared to previous reports, complete remission and survival was slightly better in our cohort, with 73% complete remission (CR) and 73% survival despite a high relapse rate (43%). After analyzing our series and performing a comprehensive and critical review of the literature, strong recommendations on appropriate management of variant APL are not possible due to the low number and heterogeneity of patients reported so far.
PubMed: 32455804
DOI: 10.3390/cancers12051313 -
Journal of Pain and Symptom Management Jun 2010Malignant fungating wounds (MFW) result from cutaneous infiltration by carcinogenic cells. Fetid odor, profuse exudate, pain, and infection are common symptoms that add... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Malignant fungating wounds (MFW) result from cutaneous infiltration by carcinogenic cells. Fetid odor, profuse exudate, pain, and infection are common symptoms that add to the physical and psychological suffering of patients with MFW. The topical treatment of MFW remains controversial.
OBJECTIVES
To collect evidence about topical treatments to control the odor of MFW.
METHODS
Fourteen sources of data were used, without restriction in terms of language, period, or study design. The patient, intervention, comparison, and outcome strategy for the development of research questions yielded 334 descriptors related to oncology, MFW, topical treatments, medications, and symptoms of these lesions. Data from the abstracts of these articles were extracted by two independent researchers and decisions were reached by consensus among them. Through an analysis of these abstracts, studies that broached the topic of MFW odor were selected. These studies were analyzed in their entirety and were classified according to quality, levels of evidence, and grade of recommendation.
RESULTS
Of 11,111 studies identified, 325 (2.93%) made reference to the control of some symptoms of MFW by means of topical interventions: 12.4% related to odor, 16.8% to exudate, 17.8% to bleeding, 31.0% to pain, and 22.0% to MFW-related infection. Within the 59 studies that analyzed odor control, seven were clinical trials (35%), five were case series (25%), and eight (40%) were case studies. Eleven topical treatments were identified. Topical metronidazole and Mesalt dressing yielded 2b level of evidence or B grade of recommendation. Activated carbon dressing and curcumin ointment yielded 2c level of evidence or B grade of recommendation. C and D grades of recommendation were observed for seven topical treatments: topical arsenic trioxide, essential oils, green tea extract, hydropolymer dressings, antiseptic solutions, hydrogels, and debridement enzymes. The variety of interventions and of the methodological quality of the studies did not allow for meta-analysis.
CONCLUSION
Of the 59 studies of odor, 20 fulfilled all the criteria for inclusion. Few studies of high quality were found, and the principal methodological flaws were the design of the studies, the sample size, and the absence of scales to measure odor. Grade B evidence for the treatment of MFW was found with topical metronidazole, Mesalt dressing, activated carbon dressing, and curcumin ointment.
Topics: Administration, Topical; Bandages; Evidence-Based Medicine; Humans; Neoplasm Metastasis; Odorants; Skin Neoplasms
PubMed: 20538188
DOI: 10.1016/j.jpainsymman.2009.11.319 -
PharmacoEconomics Jul 2019The National Institute for Health and Care Excellence (NICE) invited Teva, the company manufacturing arsenic trioxide (ATO; tradename Trisenox), to submit evidence for...
The National Institute for Health and Care Excellence (NICE) invited Teva, the company manufacturing arsenic trioxide (ATO; tradename Trisenox), to submit evidence for the clinical and cost effectiveness of ATO for untreated and relapsed or refractory acute promyelocytic leukaemia (APL). Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht University Medical Center, was commissioned as the independent Evidence Review Group (ERG). This paper presents a summary of the company submission (CS), the ERG's critical review of the clinical and cost effectiveness evidence in the CS, key methodological considerations and the development of the NICE guidance by the Appraisal Committee (AC). The CS presented three randomized controlled trials (RCTs). Two of these were trials in newly diagnosed APL (APL0406 and AML17) and the third trial was in patients with relapsed APL. Results from APL0406 showed that more people having AATO [ATO plus all-trans retinoic acid (ATRA)] were alive at 50 months compared with people having AIDA (ATRA in combination with idarubicin) (99% vs. 93%; p = 0.007). There was also a statistically significant lower cumulative incidence of relapse with AATO compared with AIDA at 50 months (2% vs. 14%; p = 0.001). At 4 years, results from AML17 showed a significant difference in event-free survival (91% vs. 70%; p = 0.002) favouring AATO but not in overall survival (93% vs. 89%; p = 0.250). The only trial presented for relapsed/refractory patients compared AATO with ATO, which was not a relevant comparison according to the NICE scope. The AC concluded that AATO was effective for untreated APL while for relapsed or refractory APL the effectiveness of ATO was considered uncertain and the long-term safety remains unexplored. In the CS base-case, AATO was less expensive (£31,088 saved) and more effective (2.546 quality-adjusted life-years (QALYs) gained) than AIDA and thus the dominating strategy for newly diagnosed low- to intermediate-risk APL. However, the ERG's critical assessment highlighted a number of concerns, including deviations from the NICE reference case and a lack of detailed description and justification of parameters and assumptions related to (the extrapolation of) treatment effectiveness. However, it was reassuring that AATO for untreated APL remained dominant in the ERG base-case, and that the worst-case scenario produced by the ERG resulted in an incremental cost-effectiveness ratio (ICER) of £21,622. The AC concluded that although there was uncertainty in the model, it could recommend ATO for both untreated and relapsed or refractory APL.
Topics: Antineoplastic Agents; Arsenic Trioxide; Cost-Benefit Analysis; Disease-Free Survival; Humans; Leukemia, Promyelocytic, Acute; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Survival Rate; Technology Assessment, Biomedical
PubMed: 30426463
DOI: 10.1007/s40273-018-0738-y