Meta-Analysis to Evaluate the Role of Interferon in Follicular Lymphoma

Purpose To determine whether interferon (IFN) -α2, when given with or following chemotherapy, influences response rate, remission duration, and survival in newly diagnosed patients with follicular lymphoma. Patients and Methods Ten phase III studies evaluating the role of IFN-α2 in 1,922 newly diagnosed patients with follicular lymphoma were analyzed. Updated individual patient data were used to perform meta-analyses for response, survival, and remission duration. Results The addition of IFN-α2 to initial chemotherapy did not significantly influence response rate. An overall meta-analysis for survival showed a significant difference in favor of IFN-α2, but also showed significant heterogeneity between studies. Further analyses were carried out in order to explain this heterogeneity, and to define the circumstances in which IFN-α2 prolonged survival. The survival advantage was seen when IFN-α2 was given: (1) in conjunction with relatively intensive initial chemotherapy (2P = .00005), (2) at a dose ≥ 5 million units (2P = .000002), (3) at a cumulative dose ≥ 36 million units per month (2P = .000008), and (4) with chemotherapy rather than as maintenance therapy (P = .004). With regard to remission duration, there was also a significant difference in favor of IFN-α2, irrespective of the intensity of chemotherapy used, IFN dose, or whether IFN was given as a maintenance strategy or with chemotherapy. Conclusion When given in the context of relatively intensive initial chemotherapy, and at a dose ≥ 5 million units (≥ 36 × 106 units per month), IFN-α2 prolongs survival and remission duration in patients with follicular lymphoma.

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How much is reasonable to expect about overall survival (OS) benefit when designing studies with new drugs for patients affected by castration resistant prostate cancer (CRPC)? Meta-analysis of 23 randomized clinical trials (RCT) including 17,640 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e16053 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e16053-e16053

Author(s):

Francesco Massari ◽

Francesca Maines ◽

Sara Pilotto ◽

Camillo Porta ◽

Paolo Carlini ◽

...

Keyword(s):

Treatment Strategy ◽

Significant Interaction ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Phase Iii ◽

Sensitivity Analyses ◽

Significant Heterogeneity ◽

Significant Difference

e16053 Background: Treatment decision making in patients affected by CRPC is difficult because the numerous available therapeutic opportunities can significantly affect OS. To demonstrate that comparing results in absence of head-to-head studies may lead to biased survival estimations, a literature-based meta-analysis was conducted. Methods: Hazard Ratios (HR) with 95% confidence intervals (CI) were extracted and cumulated according to a random-effect model from phase III trials. Sensitivity analyses were performed according to: 1) Treatment Strategy (TS, Chemotherapy versus Hormonal versus Immunotherapy versus Other), 2) Comparison (Chemotherapy versus Placebo versus Other), and 3) Disease setting with regard to treatment with Docetaxel (DOC),. Testing for heterogeneity was performed as well. Results: A significant heterogeneity for the 3 sensitivity analyses was found (p<0.0001). The cumulative HR in favor of (any) experimental arm was 0.91 (95% CI 0.84-0.99, p=0.028). We found a significant interaction according to the chosen TS (p<0.0001), in fact a significant difference in OS was more likely to be detected in RCT evaluating hormonal drugs (HR 0.76, 95% CI 0.64-0.92, p=0.005) versus studies testing immunotherapy (HR 1.16, 95% CI 0.86-1.56, p=0.31). With regard to Comparison, a significant interaction (p<0.0001) was found in favor of RCT having placebo as control (HR 0.86, 95% CI 0.76-0.97, p=0.015), versus studies evaluating chemotherapy (HR 1.00, 95% CI 0.84, 1.19, p=0.99). A significant interaction according to DOC-treatment was also detected (p<0.0001), being the Post-DOC the Setting where a significant OS benefit was more likely to be determined (HR 0.77, 95% CI 0.66-0.90, p=0.001). Conclusions: The cross-trials interpretation in absence of formal direct comparisons may drive biased conclusions with regard to OS estimation. When designing trials to evaluate drugs (or strategies) in CRPC, the expected OS benefit must take into account the comparator, the treatment strategy and the (eventual) pre-treatment with DOC.

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Maintenance Therapies for Multiple Myeloma (MM): A Direct Meta-Analysis

Blood ◽

10.1182/blood.v120.21.4271.4271 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4271-4271

Author(s):

Helen Mahony ◽

Ambuj Kumar ◽

Rahul Mhaskar ◽

Branko Miladinovic ◽

Keith Wheatley ◽

...

Keyword(s):

Maintenance Therapy ◽

Meta Analysis ◽

Phase Iii ◽

Novel Agents ◽

Controlled Trials ◽

Cochrane Central Register ◽

The Novel ◽

Significant Difference ◽

American Society

Abstract Abstract 4271 Background: The role of various maintenance therapies in the management of MM is unclear and evidence on the efficacy of these regimens is conflicting. In order to provide the totality of available randomized evidence on the role of maintenance therapy in MM, we conduct a comprehensive systematic review and meta-analysis of all RCTs studying maintenance therapy. Here, we report the pooled results of trials which directly examined the novel agents of bortezomib, lenalidomide, or thalidomide and reported the outcomes of overall survival (OS) and/or progression-free survival (PFS). Methods: A comprehensive literature search of MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and meetings abstracts from American Society of Hematology, American Society of Clinical Oncology, European Society for Medical Oncology and European Hematology Association was undertaken to identify all phase III randomized controlled trials (RCTs) of maintenance therapy published until July 2012. We extracted data on OS and PFS. Time to event data were pooled under the random effects model as hazard ratios (HR) and its corresponding 95% confidence interval (CI). Heterogeneity was assessed using the chi square test and I2statistic. All analyses were done in Review Manager 5.1. Results: Twenty-two RCTs met the inclusion criteria. (Figure 1) However, only data from the following RCTs were able to be pooled for the direct head-to-head comparison: 2 RCTs of bortezomib maintenance therapy enrolling 792 patients, 5 RCTs of lenalidomide maintenance therapy enrolling 1776 patients, 11 RCTs of thalidomide maintenance therapy enrolling 3952 patients. The pooled HR and 95% CI, number of RCTs, and number of patients for each comparison are presented in Figure 2. Only two trials compared the novel agents of bortezomib and thalidomide head-to-head. There was no significant different in terms of PFS. For the novel agent of lenalidomide, there was no significant difference is OS compared to placebo. The pooled PFS was in favor of lenalidomide maintenance compared to placebo. For thalidomide, OS was significantly in favor of the intervention when compared to placebo or prednisone/dexamethasone. There was no significant difference in OS between thalidomide maintenance when compared to interferon control. For the outcome of PFS, the pooled results favored thalidomide when compared to prednisone/dexamethasone or interferon control. There was no significant difference between thalidomide and placebo. Conclusion: To date, the largest number of trials has been among thalidomide as maintenance therapy. In our meta-analysis, thalidomide is the only agent which improves survival compared to no treatment. Other novel agents have been evaluated in a smaller number of trials and current data does not allow for firm conclusions that any agent is superior to the other. An indirect, network meta-analysis is called for to provide additional insights regarding comparative efficacy of the novel agents as the maintenance treatment for MM. Disclosures: No relevant conflicts of interest to declare.

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Autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma (MM) in the era of novel agents: A meta-analysis of phase III randomized controlled trials.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8022 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8022-8022

Author(s):

Binod Dhakal ◽

Saurabh Chhabra ◽

Mehdi Hamadani ◽

Anita D'souza ◽

Saad Zafar Usmani ◽

...

Keyword(s):

Stem Cell ◽

Meta Analysis ◽

Phase Iii ◽

Novel Agents ◽

High Dose ◽

Significant Heterogeneity ◽

Cell Transplant ◽

The Novel ◽

Novel Agent

8022 Background: Given the unprecedented deep response rates with the novel agent induction, the role of high dose therapy (HDT) followed by ASCT in MM pts. has been questioned, and was re-evaluated in a number of randomized clinical trials (RCTs). Although, the results of most studies suggest the continued benefit of HDT/ASCT, some RCTs suggest no overall survival (OS) benefit. We undertook a systematic review and meta-analysis of phase III randomized RCTs evaluating the role of HDT compared to standard therapy (SDT) in the context of novel agent induction Methods: We searched the PubMed, Scopus and Cochrane Collection of Controlled Trial databases using the term myeloma combined with autologous or transplant or myeloablative or stem cell from 2000-2016. A total of 2480 articles identified, of which 4 large phase III RCTs compared upfront HDT with SDT with novel agents use. Two individuals independently extracted the data. Reported hazard ratio (HR) and survival data were pooled using random effects models (STATA v14, College Station, Tx). Heterogeneity was assessed using I2. Results: Four studies comprising 2421 patients were included (Table 1). One study did not report the HR for death and hence OS analysis was limited to 3 studies. The combined hazard for progression with HDT was 0.55 (95% CI 0.40-0.71) (p < 0.005). The combined hazard for death with HDT was 0.65 (95% CI 0.29-1.0) (p = 0.007). Sensitivity and sub-group analysis showed no difference in PFS (p = 0.06) and OS (p = 0.22) with HDT. Significant heterogeneity was demonstrated by I2 of 71.4% for PFS (p = 0.01) and 68.4% for OS (p = 0.04). Conclusions: Based on our analysis, even in the novel agent era, HDT appears to be beneficial and should be considered standard of care for all transplant eligible MM pts. [Table: see text]

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Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: Part 1 Newly diagnosed disease

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab028 ◽

2021 ◽

Author(s):

Shervin Taslimi ◽

Vincent Ye ◽

Gelareh Zadeh

Keyword(s):

Randomized Clinical Trials ◽

Meta Analysis ◽

Progression Free Survival ◽

Standard Of Care ◽

Lessons Learned ◽

Significant Heterogeneity ◽

Newly Diagnosed ◽

Dismal Prognosis ◽

Treatment Comparisons ◽

Meta Analyses

Abstract Background Glioblastoma (GB) is the most common malignant brain tumour with a dismal prognosis despite standard of care (SOC). Here we used a network meta-analysis on treatments from randomized control trials (RCT) to assess effect on Overall survival (OS) and progression free survival (PFS) beyond the SOC. Methods We included RCT’s which investigated the addition of a new treatment to the SOC in patients with newly diagnosed GB. Our primary outcome was OS, with secondary outcomes including PFS and adverse reactions. Hazard ratio and its 95% confidence interval (CI) regarding OS and PFS were extracted from each paper. We utilized a frequentist network meta-analysis. We planned a subgroup analysis based on MGMT status. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Results Twenty-one studies were included representing a total of 7403 patients with GB. There was significant heterogeneity among studies impacting important factors such as timing of randomization, and sample size. A confidence analysis on the network meta-analysis results revealed a score of Low or Very Low for all treatment comparisons, across subgroups. Allowing for the hetereogeneity within the study population, Alkylating-nitrosureas (Lomustine and ACNU) and Tumor treating field (TTF) improved both OS (HR=0.53, 95%CI 0.33-0.84 and HR=0.63 95%CI 0.42-0.94 respectively) and PFS (HR=0.88, 95%CI 0.77-1.00 and HR=0.63 95%CI 0.52-0.76 respectively). Conclusions Our analysis highlights the numerous studies performed on newly diagnosed GB, with no proven consensus treatment that is superior to the current SOC. Inter-trial heterogeneity raises the need for better standardization in neuro-oncology studies.

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Consolidation Therapy Based on Conventional Chemotherapy and Corticoids Do Not Provide Therapeutic Advantage for Newly Diagnosed Patients after Autologous Transplantation.

Blood ◽

10.1182/blood.v110.11.531.531 ◽

2007 ◽

Vol 110 (11) ◽

pp. 531-531 ◽

Cited By ~ 1

Author(s):

Roman Hajek Prof ◽

Ivan Spicka ◽

Vlastimil Scudla ◽

Evzen Gregora ◽

Vladimir Maisnar ◽

...

Keyword(s):

Maintenance Therapy ◽

Response Rate ◽

Autologous Transplantation ◽

Phase Iii ◽

Primary Therapy ◽

Consolidation Therapy ◽

Newly Diagnosed ◽

Conventional Chemotherapy ◽

Significant Difference ◽

Phase Iii Study

Abstract Benefit of maintenance and/or consolidation therapy after autologous transplantation (AT) is unclear. CMG 2002 is randomized phase III study comparing efficacy and safety of consolidation therapy versus interferon alfa (IFN) maintenance therapy after AT in patients with newly diagnosed multiple myeloma (MM). Methods: A total of 545 patients were enrolled to the trial in the period of April 2002 to April 2007. This first analysis (patients enrolled until December 31, 2005) was done in cohort of 269 patients randomly assigned after AT to either IFN 3x3 MU s.c. weekly alone (IFN group) until relapse or four cycles of chemotherapy CED (cyclophosphamide 300–400 mg/m2 i.v., etoposide 30–40mg/m2 i.v., and dexamethasone 40mg on days 1–4; month 4,8,12 and 16 after transplantation; CED group) followed by IFN 3x3 MU s.c. weekly starting month 18 after AT. All patients received primary therapy with four cycles of VAD regimen (vincristine, doxorubicine, and dexamethasone) followed by mobilization with cyclophosphamide 2.5g/m2 and G-CSF 5–10 μg/kg. The conditioning regimen with melphalan 200mg/m2 was used for single AT. Response was defined according to Blade’s criteria. Median of follow up is 41 months (range 6.2–56.1) Results: All basic parameters including median age, gender distribution, measures of disease burden, renal function and also response rate before/after AT, and basic prognostic factors (beta2microglobulin, albumin, LDH, CRP) were comparable between randomized IFN group (n=134) and CED group (n=135) as follows: median age 57.0 vs. 57.0; stage I: 8.1% vs. 5.5%, stage II: 27% vs. 27.3%, stage III: 64.9% vs. 66.7%; stage B 12.8% vs. 17.1%; ISS I: 37.2% vs. 34.0%, ISS II: 29.7% vs. 34.0%, ISS III: 17.6% vs.21.8%, ISS not available: 15.5 vs.10.2%; IgA: 25.7% vs. 29.9%, IgG: 61.5% vs. 51.8%; ORR after AT (CR+PR): 72.3% vs.72.1%, CR: 23.0% vs. 19.0%, VGPR: 17.6 vs. 24.5%, PR 31.8% vs. 28.6%). Four cycles of CED consolidation treatment after AT did not significantly increase response rate achieved after AT in comparison with IFN group (response rate improved in 14,8% in CED group vs. 15,1% in IFN group at 4 months, respectively in 81,5% vs. 75,8% at 18 months after AT). There was no significant difference between CED and IFN groups in time to progression [TTP] (median 34.5 vs.38.2 months, p=0.622), in progression free survival [PFS] (median 32.4 vs. 36.8 months, p=0.515) and also in duration of response [DOR] (29.6 vs. 36.2 months). Median of overall survival was not yet reached (25th percentile 40.8 months for all patients). CED consolidation had acceptable toxic profile. Conclusions: In the first analysis of CMG 2002 randomized phase III study consolidation therapy based on conventional chemotherapy and corticoids followed by IFN maintenance therapy did not show any benefit for patients if compared with IFN maintenance alone.

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A network meta-analysis (NMA) of randomized controlled trials (RCT) of chemotherapy regimens for metastatic pancreatic cancer (mPC).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4050 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4050-4050 ◽

Cited By ~ 1

Author(s):

Gillian Gresham ◽

Sharlene Gill ◽

George A Wells ◽

Derek J. Jonker

Keyword(s):

Pancreatic Cancer ◽

Survival Benefit ◽

Meta Analysis ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Phase Iii ◽

Significant Heterogeneity ◽

Treatment Protocols ◽

Significant Difference ◽

Safety Outcomes

4050 Background: Recent RCTs suggest a survival benefit for combination therapy in mPC compared to gemcitabine alone. Such combinations include FOLFIRINOX and gemcitabine plus nab-paclitaxel (G+nab-P). Survival and safety outcomes of these regimens were analyzed using gemcitabine as the reference comparator. Methods: Systematic review and NMA included data from reported phase III RCTs meeting quality standards and compared chemotherapy treatment to gemcitabine for mPC between 2000 and 2013. Excluded were trials assessing locally advanced pancreatic cancer. Following inter-trial heterogeneity assessment (patient characteristics, trial methodologies, treatment protocols), Bayesian NMAs were conducted for primary (overall survival [OS]) and secondary (progression free survival [PFS]) outcomes, overall response rate [ORR], and safety. Results: 27 studies were included involving 10 429 patients and 18 different treatments. No significant heterogeneity was observed between trials. When indirectly compared, FOLFIRINOX, PEFG and G+nab-P were top ranked for OS, PFS and ORR (Table). Comparing FOLFIRINOX and G +nab-P, there was no significant difference in odds ratios (OR) for febrile neutropenia, diarrhea or sensory neuropathy. FOLFIRINOX caused more gr3-4 neutropenia (OR 1.85 (95%Cl 1.1-3.4),p<0.05), and G+nab-P trended more gr3-4 fatigue (OR 2.03 95% Cl 0.95-3.8). Conclusions: Survival and safety outcomes were comparable amongst the three regimens identified from this network meta-analysis for mPC. FOLFIRINOX tended towards a greater survival benefit over G+nab-P and PEFG although comparisons did not reach statistical significance.Head-to-head trials between FOLFIRINOX, G+nab-P and PEFG are needed to further compare the survival benefits and safety profiles of these treatments. [Table: see text]

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Laser Influence on Dental Sensitivity Compared to Other Light Sources Used During In-office Dental Bleaching: Systematic Review and Meta-analysis

Operative Dentistry ◽

10.2341/19-064-l ◽

2020 ◽

Vol 45 (6) ◽

pp. 589-597

Author(s):

BGS Casado ◽

EP Pellizzer ◽

JR Souto Maior ◽

CAA Lemos ◽

BCE Vasconcelos ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Color Change ◽

Meta Analysis ◽

Present Review ◽

Cochrane Library ◽

Light Sources ◽

Eligibility Criteria ◽

Tooth Color ◽

Significant Difference ◽

Meta Analyses

Clinical Relevance The use of laser light during bleaching will not reduce the incidence or severity of sensitivity and will not increase the degree of color change compared with nonlaser light sources. SUMMARY Objective: To evaluate whether the use of laser during in-office bleaching promotes a reduction in dental sensitivity after bleaching compared with other light sources. Methods: The present review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and is registered with PROSPERO (CDR42018096591). Searches were conducted in the PubMed/Medline, Web of Science, and Cochrane Library databases for relevant articles published up to August 2018. Only randomized clinical trials among adults that compared the use of laser during in-office whitening and other light sources were considered eligible. Results: After analysis of the texts retrieved during the database search, six articles met the eligibility criteria and were selected for the present review. For the outcome dental sensitivity, no significant difference was found favoring any type of light either for intensity (mean difference [MD]: −1.60; confidence interval [CI]: −3.42 to 0.22; p=0.09) or incidence (MD: 1.00; CI: 0.755 to 1.33; p=1.00). Regarding change in tooth color, no significant differences were found between the use of the laser and other light sources (MD: −2.22; CI: −6.36 to 1.93; p=0.29). Conclusions: Within the limitations of the present study, laser exerts no influence on tooth sensitivity compared with other light sources when used during in-office bleaching. The included studies demonstrated that laser use during in-office bleaching may have no influence on tooth color change.

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Management of anticoagulants in delayed bleeding after endoscopic resection: A systematic review and meta-analysis

Endoscopy International Open ◽

10.1055/a-1467-6068 ◽

2021 ◽

Vol 09 (07) ◽

pp. E1128-E1135

Author(s):

Xianhong Zhao ◽

Yangxue Huang ◽

Jiarong Li ◽

Aoqiang Zhou ◽

Gengxin Chen ◽

...

Keyword(s):

Endoscopic Resection ◽

Clinical Effect ◽

Meta Analysis ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Delayed Bleeding ◽

Best Management ◽

Significant Difference ◽

Meta Analyses ◽

Bridge Therapy

Abstract Background and study aims Delayed bleeding and thrombotic events are uncontrolled adverse events that are hard to balance in patients receiving anticoagulants after endoscopic resection. The present study aims to assess the clinical effect of warfarin, when compared to direct oral anticoagulants (DOACs), in terms of delayed bleeding and thrombotic events. Methods A comprehensive electronic literature search was conducted for eligible literature. Pairwise meta-analyses were performed on outcomes of delayed bleeding and thrombotic events. Two networks within the Bayesian framework were established based on the management of anticoagulants and type of DOAC. Results Eight cohort studies with 2,046 patients were eligible for inclusion, including 1,176 patients treated with warfarin and 870 with DOACs. There was no significant difference between warfarin and DOACs, in terms of delayed bleeding (OR = 1.29, 95 % CI [0.99–1.69]) and thromboembolism (OR = 2.0, 95 % CI [0.32–12.39]). In the network meta-analyses for delayed bleeding, the rank probabilities revealed that the safest management was discontinuous warfarin without heparin bridge therapy (HBT). Rank probabilities for the types of DOACs demonstrated that the safest drug was dabigatran. Conclusions There was no significant difference in delayed bleeding and thromboembolism between warfarin and DOACs in patients receiving endoscopic treatment. In terms of delayed bleeding, discontinuous warfarin without HBT was suggested as the best management, and dabigatran was recommended as the best type of DOAC.

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The high risk of malarial recurrence in patients with Plasmodium-mixed infection after treatment with antimalarial drugs: a systematic review and meta-analysis

Parasites & Vectors ◽

10.1186/s13071-021-04792-5 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Aongart Mahittikorn ◽

Frederick Ramirez Masangkay ◽

Kwuntida Uthaisar Kotepui ◽

Giovanni De Jesus Milanez ◽

Manas Kotepui

Keyword(s):

Systematic Review ◽

Mixed Infection ◽

Subgroup Analysis ◽

Initial Treatment ◽

Meta Analysis ◽

Antimalarial Drugs ◽

Secondary Outcome ◽

Significant Heterogeneity ◽

Pooled Prevalence ◽

Significant Difference

Abstract Background Malaria mixed infections are often unrecognized by microscopists in the hospitals, and a delay or failure to treat Plasmodium-mixed infection may lead to aggravated morbidity and increased mortality. The present study aimed to quantify the pooled proportion and risk of malarial recurrences after the treatment of Plasmodium-mixed infection. The results of the study may provide benefits in the management of Plasmodium-mixed infection in co-endemic regions. Methods This systematic review and meta-analysis searched the international Prospective Register of Systematic Reviews (PROSPERO; ID = CRD42020199709), MEDLINE, Web of Science, and Scopus for potentially relevant studies in any language published between January 1, 1936, and July 20, 2020, assessing drug efficacy in patients with Plasmodium-mixed infection. The primary outcome was the pooled prevalence of Plasmodium parasitemia after initiating antimalarial treatment for Plasmodium-mixed infection. The secondary outcome was the pooled risk ratio (RR) of malarial recurrence in Plasmodium-mixed infection compared with those in Plasmodium falciparum and Plasmodium vivax mono-infection. The pooled analyses were calculated by random-effects meta-analysis. After the initial treatment in different days of recurrences (≤ 28 days or > 28 days), the risk of Plasmodium parasitemia was compared in subgroup analysis. Results Out of 5217 screened studies, 11 were included in the meta-analysis, including 4390 patients from six countries. The pooled prevalence of all recurrences of Plasmodium-mixed parasitemia was 30% (95% confidence interval (CI) 16–43; I2: 99.2%; 11 studies). The RR of malarial recurrence within 28 days after the initial treatment (clinical treatment failure) of Plasmodium-mixed parasitemia compared with the treatment of P. falciparum was 1.22 (p: 0.029; 95% CI 1.02–1.47; Cochran Q: 0.93; I2: 0%; six studies), while there was no significant difference in the risk of recurrence 28 days after initial treatment compared with the treatment of P. falciparum (p: 0.696, RR: 1.14; 95% CI 0.59–2.18; Cochran Q < 0.05; I2: 98.2%; four studies). The subgroup analysis of antimalarial drugs showed that significant malarial recurrence within 28 days was observed in patients treated with artemisinin-based combination therapies (ACTs) with no significant heterogeneity (p: 0.028, RR: 1.31; 95% CI 1.03–1.66; Cochran Q: 0.834; I2: 0%). Conclusions The present findings showed a high prevalence of malarial recurrence after the initial treatment of Plasmodium-mixed infection. Moreover, significant malaria recurrence of mixed infection occurred within 28 days after treatment with ACTs. Graphic Abstract

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Comparison of irinotecan and oxaliplatin as the first-line therapies for metastatic colorectal cancer: a meta-analysis

BMC Cancer ◽

10.1186/s12885-021-07823-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sadayuki Kawai ◽

Nozomi Takeshima ◽

Yu Hayasaka ◽

Akifumi Notsu ◽

Mutsumi Yamazaki ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Controlled Trials ◽

Significant Heterogeneity ◽

Cochrane Central Register ◽

First Line ◽

Anti Vegf ◽

Significant Difference ◽

High Incidence

Abstract Background Irinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC. Methods This meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Results Nineteen trials involving 4571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82–0.98, P = 0.02), but not with OS (pooled HR = 0.91, 95% CI = 0.80–1.03, P = 0.15). Conclusion Although the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. The combination of anti-VEGF antibody and IRI was associated with better PFS compared with anti-VEGF antibody and Ox. Both regimens could be used as the first-line treatments for mCRC with consideration of the patients’ condition or toxicity profiles.

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