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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 -
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 -
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 -
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 -
Cancer Reports (Hoboken, N.J.) Mar 2024Recent advances in the treatment of acute promyelocytic leukemia (APML) have seen unprecedented improvements in patient outcomes. However, such rapid growth in... (Review)
Review
BACKGROUND
Recent advances in the treatment of acute promyelocytic leukemia (APML) have seen unprecedented improvements in patient outcomes. However, such rapid growth in understanding often leads to uncertainty regarding superiority among candidate treatment regimens, especially when further scrutinized from an epidemiological perspective.
AIMS
The aim of this systematic review with epidemiological analysis was to identify and compare commonly utilized protocols for standard-risk APML with a particular focus on complete remission (CR), overall/disease-free survival (DFS), and reported adverse events.
METHODS AND RESULTS
Medline, Scopus, and CINAHL were interrogated to identify studies utilizing all-trans retinoic acid (ATRA) in addition to arsenic trioxide (ATO) and/or anthracyclines such as idarubicin (IDA) in the treatment of de-novo APML. After collation of studies, an epidemiological analysis was subsequently performed to compare protocols with regards to outcomes of interest using number needed to benefit (NNB) and number needed to harm (NNH) measures. Seventeen articles, describing 12 distinct trials, were included in the analysis. These trials made use of three unique protocols; CR rates were 94%-100% for ATO/ATRA regimens, 95%-96% for ATO/ATRA/anthracycline regimens, and 89%-94% for ATRA/anthracycline regimens. Epidemiological analysis demonstrated NNB for CR was 9.09 (ATO/ATRA vs. ATRA/IDA) and 20.00 (ATO/ATRA vs. ATO/ATRA/IDA), NNH for neutropenia was -3.45 (ATO/ATRA vs. ATRA/IDA), and NNH for infection was -3.13 (ATO/ATRA vs. ATRA/IDA) and -1.89 (ATO/ATRA vs. ATO/ATRA/IDA).
CONCLUSION
The ATO/ATRA regimen is superior to chemotherapy-containing protocols at inducing remission and promoting survival in patients with APML. The regimen is better tolerated than the proposed alternatives with fewer adverse events. Future research opportunities include quantifying APML epidemiology and pursuing oral arsenic as an option for simplification of therapeutic protocols.
Topics: Humans; Leukemia, Promyelocytic, Acute; Anthracyclines; Arsenicals; Oxides; Treatment Outcome; Tretinoin; Antibiotics, Antineoplastic; Pathologic Complete Response
PubMed: 38507294
DOI: 10.1002/cnr2.2035 -
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 -
Journal of Clinical Medicine Oct 2020Differentiation syndrome (DS) is a potentially fatal adverse drug reaction caused by the so-called differentiating agents such as all-trans retinoic acid (ATRA) and... (Review)
Review
Differentiation syndrome (DS) is a potentially fatal adverse drug reaction caused by the so-called differentiating agents such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), used for remission induction in the treatment of the M3 subtype of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL). However, recent DS reports in trials of isocitrate dehydrogenase (IDH)-inhibitor drugs in patients with IDH-mutated AML have raised concerns. Given the limited knowledge of the incidence of DS with differentiating agents, we conducted a systematic literature review of clinical trials with reports of DS to provide a comprehensive overview of the medications associated with DS. In particular, we focused on the incidence of DS reported among the IDH-inhibitors, compared to existing ATRA and ATO therapies. We identified 44 published articles, encompassing 39 clinical trials, including 6949 patients. Overall, the cumulative incidence of DS across all treatment regimens was 17.7%. Incidence of DS was notably lower in trials with IDH-inhibitors (10.4%) compared to other regimens, including ATRA and/or ATO (15.4-20.6%). Compared to other therapies, the median time to onset was four times longer with IDH-inhibitors (48 vs. 11 days). Treating oncologists should be mindful of this potentially fatal adverse drug reaction, as we expect the current trials represent an underestimation of the actual incidence.
PubMed: 33081000
DOI: 10.3390/jcm9103342 -
Cancers Apr 2020The management of pregnant women with acute promyelocytic leukemia (APL) is a challenging situation where limited evidence-based information is available. We performed a...
The management of pregnant women with acute promyelocytic leukemia (APL) is a challenging situation where limited evidence-based information is available. We performed a systematic literature review to analyze the outcomes reported for both mother and fetus when APL is diagnosed during pregnancy. PubMed, Scopus and Web of Science databases were systematically searched to identify studies reporting cases of APL during pregnancy. Sixty-six articles met the eligibility criteria (53 single case reports). Ninety-two patients were eligible for induction therapy, with most them being treated with all-trans retinoic acid alone (32%) or combined with chemotherapy (43%), while the remaining patients received chemotherapy alone. Three patients were treated with arsenic-based regimens after delivery. Overall complete remission rate was 89%, with no statistically significant differences according to the type of induction and gestational age. During the first trimester, women were more likely to experience spontaneous and induced abortion compared to those during the second trimester (88% vs. 30%) ( < 0.0001), while only one patient diagnosed during the third trimester terminated in stillbirth. Twelve of 16 infants with neonatal complications had respiratory distress syndrome. Except two early deaths (Potter's syndrome and pulmonary hemorrhage), all neonates evolved favorably. This study confirms that gestational age does not affect the results in the mother, but is closely related to fetal viability. Our results may be useful for the process of decision making that requires the involvement of the patient, hematologist, obstetrician and neonatologist.
PubMed: 32295152
DOI: 10.3390/cancers12040968