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Expert Review of Hematology Aug 2020To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and A+AVD (brentuximab vedotin, with doxorubicin, vinblastine, and dacarbazine) for advanced-stage Hodgkin lymphoma (HL).
METHODS
A systematic literature review (SLR) was conducted on 29 July 2016 (updated 26 July 2018) to identify randomized controlled trials (RCTs) and non-RCTs assessing the treatment of newly-diagnosed advanced-stage HL with ABVD and BEACOPP (and their variants), and A+AVD.
RESULTS
The SLR identified 62 RCTs and 42 non-RCTs. Five-year overall survival rates for ABVD and BEACOPP were 60-97% and 84-99%, and 5-year progression-free survival rates were 58-81% and 83-96%, respectively. Both regimens were associated with tolerability issues and side effects. Discontinuation or dose reduction of bleomycin resulted in fewer adverse events, without significantly affecting efficacy. A head-to-head trial demonstrated improved efficacy for A+AVD vs ABVD, with an acceptable tolerability profile. No data from head-to-head trials comparing A+AVD with BEACOPP were available, and an indirect treatment comparison was not feasible.
CONCLUSION
New therapies, such as A+AVD, maintain the efficacy observed with current treatments, and may provide a more tolerable treatment option for patients with advanced-stage HL.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Diagnostic Imaging; Disease Management; Hodgkin Disease; Humans; Neoplasm Staging; Prognosis; Publication Bias; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32749937
DOI: 10.1080/17474086.2020.1793666 -
JAMA Network Open Mar 2020Since 2011, immune checkpoint inhibitors (ICIs) have been effective treatment options for advanced melanoma. Little is known about how risks of immune-related adverse... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Since 2011, immune checkpoint inhibitors (ICIs) have been effective treatment options for advanced melanoma. Little is known about how risks of immune-related adverse events (irAEs) vary by ICIs.
OBJECTIVE
To compare the risk of irAEs across different treatment regimens for advanced melanoma using network meta-analysis.
DATA SOURCES
PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched for all randomized clinical trial (RCT) articles published from January 1, 2010, through June 30, 2019.
STUDY SELECTION
Studies included phases 2 and 3 RCTs in the treatment of advanced melanoma that compared ICIs (ipilimumab, nivolumab, and pembrolizumab) with chemotherapy drugs (eg, dacarbazine, carboplatin, and paclitaxel) or different ICI regimens.
DATA EXTRACTION AND SYNTHESIS
Different treatment regimens were compared using bayesian network meta-analysis with Markov chain Monte Carlo simulation with noninformative prior distribution and random-effects generalized linear models.
MAIN OUTCOMES AND MEASURES
Primary outcomes were the cumulative incidence of any irAEs (regardless of severity) and severe irAEs (grades 3-5). Based on the pooled odds ratios (ORs) and 95% credible intervals (95% CrI), the probability of being associated with the lowest irAE risks was estimated for each treatment regimen.
RESULTS
Nine RCTs with 8 different treatment regimens for advanced melanoma and involving a total of 5051 patients were included. Overall, the 3 ICI treatment regimens associated with the lowest risk of any or severe irAEs were pembrolizumab, 2 mg/kg, every 3 weeks; nivolumab, 3 mg/kg, every 2 weeks; and pembrolizumab, 10 mg/kg, every 3 weeks. Compared with ipilimumab, 10 mg/kg, every 3 weeks, only nivolumab, 3 mg/kg, every 2 weeks, was associated with a decreased risk for any irAEs (OR, 0.34; 95% CrI, 0.13-0.94). A decreased risk for severe irAEs was observed for ipilimumab, 3 mg/kg, every 3 weeks (OR, 0.35; 95% CrI, 0.14-0.74); pembrolizumab, 10 mg/kg, every 2 weeks (OR, 0.22; 95% CrI, 0.05-0.95) and 10 mg/kg every 3 weeks (OR, 0.20; 95% CrI, 0.06-0.68); and nivolumab, 3 mg/kg, every 2 weeks (OR, 0.20; 95% CrI, 0.07-0.48) compared with ipilimumab, 10 mg/kg, every 3 weeks. An increased risk for severe irAEs was associated with nivolumab, 1 mg/kg, every 3 weeks combined with ipilimumab, 3 mg/kg, every 3 weeks compared with other ICI regimens (ORs ranging from 4.09 [95% CrI, 1.73-10.99] to 7.40 [95% CrI, 1.12-49.29]) except ipilimumab, 10 mg/kg, every 3 weeks.
CONCLUSIONS AND RELEVANCE
These findings suggest that for patients with advanced melanoma at high risk of irAEs, pembrolizumab, 2 mg/kg, every 3 weeks, nivolumab, 3 mg/kg, every 2 weeks, and pembrolizumab, 10 mg/kg, every 3 weeks may be the preferred treatment regimens (with respect to irAE risks) among the ICI regimens reported, whereas ipilimumab, 10 mg/kg, every 3 weeks alone and nivolumab, 1 mg/kg, every 3 weeks combined with ipilimumab, 3 mg/kg, every 3 weeks should be used with caution. A network analysis may be valuable for clinical decision-making when evidence from head-to-head comparisons is lacking.
Topics: Aged; Antineoplastic Agents; Antineoplastic Agents, Immunological; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Melanoma; Middle Aged; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 32211869
DOI: 10.1001/jamanetworkopen.2020.1611 -
Critical Reviews in Oncology/hematology Jan 2022Conduct a systematic review of the effectiveness of systemic therapies for adult recurrent glioblastoma (rGBM). (Review)
Review
AIM
Conduct a systematic review of the effectiveness of systemic therapies for adult recurrent glioblastoma (rGBM).
METHODS
We electronically searched for randomized controlled trials from three major databases and four conferences from 2009-Dec 2020. Two independent reviewers conducted screening, data extraction, and quality assessment.
RESULTS
48 randomized trials were identified. Outcome reporting was inconsistent: overall survival (OS) in 46 studies, progression free survival in 37 studies, 6-month PFS in 30 studies, objective response rate in 28 studies, and 6-month OS in 7 studies. Network meta-analysis was not feasible due to heterogeneity in outcome reporting and single-study linkages. Most studies compared lomustine (8 studies), bevacizumab (18), or temozolomide (8) with other treatments. The median OS across all studies ranged from 3 to 17.6 months.
CONCLUSIONS
Based on level one evidence, there is no superior systemic regimen for rGBM. rGBM is a heterogeneous population with no single regimen demonstrating OS benefit. Registration number: CRD42020148512.
Topics: Adult; Bevacizumab; Brain Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Progression-Free Survival; Randomized Controlled Trials as Topic; Temozolomide
PubMed: 34808376
DOI: 10.1016/j.critrevonc.2021.103540 -
Acta Neurologica Belgica Dec 2021Gliosarcoma (GSM) is a rare central nervous system tumor. Clinical management of it is similar to glioblastoma (GBM). However, due to a few comparative studies exist,... (Meta-Analysis)
Meta-Analysis
Gliosarcoma (GSM) is a rare central nervous system tumor. Clinical management of it is similar to glioblastoma (GBM). However, due to a few comparative studies exist, uncertainty and disagreements remain in the literatures. To assess the available evidence on the value of different treatments and to carry out an up-to-date evaluation to summarize the evidence for the optimal treatment in GSM patients. Free words were used to search for the relevant studies without language limitations in electronic databases including PubMed, Ovid EMBASE, Cochrane Central Register of Controlled Trials from inception to September 15, 2019. Pooled hazard ratio (HR) with 95% confidence interval (CI) were calculated using a random-effects model. The main endpoint was all-cause mortality. Overall, 10 studies published between 2008 and 2018 including 803 patients were selected for the meta-analysis. Temozolomide (TMZ)-dominated chemotherapy was associated with a reduced risk of overall survival (OS), with HR 0.49 (95% CI 0.37-0.66). The pooled HR of OS was 0.40 (95% CI 0.29-0.56) between radiotherapy and without radiotherapy. The pooled HR (0.52, 95% CI 0.32-0.85) indicated gross total resection (GTR) had a positive impact on OS in GSM. In patients with GSM, survival benefits as currently performed are associated with TMZ-dominated chemotherapy and high-dose radiotherapy. Our systematic review and meta-analysis also demonstrate GTR is associated with a reduction in all-cause mortality in patients with primary GSM.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; Gliosarcoma; Humans; Temozolomide; Treatment Outcome
PubMed: 33156945
DOI: 10.1007/s13760-020-01533-w -
Journal of Controlled Release :... Sep 2021Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Despite the gold standard treatment combining surgical resection, radiation and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Despite the gold standard treatment combining surgical resection, radiation and adjuvant plus concomitant chemotherapy with the alkylating agent temozolomide (TMZ), the prognosis remains poor (5-year survival rate < 10%). Over the last three decades, a vast array of drug delivery systems (DDS) have been developed for the local treatment of GBM, with the majority of the characterization being undertaken in pre-clinical models. We aimed to gain an overview of the potential efficacy of such local delivery systems in comparison to the systemic drug administration.
METHODS
In this paper, a systematic search of Pubmed, Web of Science, and Scopus was performed using pre-determined search terms. Studies were assessed for eligibility based on specific inclusion and exclusion criteria. A total of fifteen publications were included for analysis of local vs systemic group median survival, tumor volume and adverse events, with five brought forward for a meta-analysis.
RESULTS
The majority of studies showed local delivery to be more efficacious than systemic administration, regardless of the drug, animal model, type of DDS used, or duration of the study. The meta-analysis also showed that the mean difference between median survival ratios was statistically significantly in favor of local delivery.
CONCLUSION
Preclinical evidence shows that there is a firm rationale for further developing DDS for local therapeutic delivery to GBM and other brain cancers.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Dacarbazine; Drug Delivery Systems; Glioblastoma; Humans; Pharmaceutical Preparations
PubMed: 34298055
DOI: 10.1016/j.jconrel.2021.07.031 -
Pigment Cell & Melanoma Research May 2024Dacarbazine (DTIC) and its oral counterpart temozolomide (TMZ) have been the most used agents in advanced malignant melanoma (MM) patients and they are still used... (Meta-Analysis)
Meta-Analysis
Dacarbazine (DTIC) and its oral counterpart temozolomide (TMZ) have been the most used agents in advanced malignant melanoma (MM) patients and they are still used routinely. The preferred first line treatment, immune checkpoint inhibitors (CPIs) might shape the tumor and the tumor microenvironment, possibly affecting the response to subsequent therapies. The aim of this study was to investigate the treatment effect of DTIC/TMZ in MM patients after CPI therapy in a consecutive patient cohort and through systematic literature review and meta-analysis. Thirty-five patients with advanced MM treated with DTIC/TMZ after previous CPI therapy in three Swedish regions between 2017 and 2021 were recognized and seven case series studies were identified through systematic database review. Pooled data from all 345 patients showed a median real-world progression-free survival (rwPFS) of 1.9 months and overall survival (OS) of 6.0 months. Three of these studies were included in a meta-analysis comparing DTIC/TMZ after CPI treatment, versus no previous immunotherapy, showing no statistically significant differences in rwPFS or OS but higher real-world response rate to chemotherapy for the prior-CPI treated group (Odds Ratio: 2.24; 95% Confidence Interval: 1.04-4.86). The current study supports consideration of DTIC/TMZ in later line of treatment in the immunotherapy era.
Topics: Humans; Temozolomide; Melanoma; Immune Checkpoint Inhibitors; Dacarbazine; Female; Male; Aged; Middle Aged; Adult; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Skin Neoplasms
PubMed: 38158376
DOI: 10.1111/pcmr.13156 -
International Journal of Radiation... Oct 2021Limited evidence is available on the utility of dose-escalated radiation therapy (DE-RT) with or without temozolomide (TMZ) versus standard-of-care radiation therapy... (Meta-Analysis)
Meta-Analysis
PURPOSE
Limited evidence is available on the utility of dose-escalated radiation therapy (DE-RT) with or without temozolomide (TMZ) versus standard-of-care radiation therapy (SoC-RT) for patients with newly diagnosed glioblastoma multiforme. We performed a systematic review/meta-analysis to compare overall survival (OS) and progression-free survival (PFS) between DE-RT and SoC-RT.
METHODS AND MATERIALS
We used a Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses/Meta-analysis of Observational Studies in Epidemiology selection criterion to identify studies. The primary and secondary outcomes were 1-year OS and 1-year PFS, respectively. Outcomes and comparisons were subdivided based on receipt of TMZ and MGMT status. DE-RT was defined based on equivalent dose calculations. Random effects meta-analyses using the Knapp-Hartung correction, arcsine transformation, and restricted maximum likelihood method were conducted. Meta-regression was used to compare therapeutic (eg, DE-RT or TMZ) and pathologic characteristics (eg, MGMT methylation status) using the Wald-type test.
RESULTS
Across 22 published studies, 2198 patients with glioblastoma multiforme were included; 507 received DE-RT. One-year OS after DE-RT alone was higher than SoC-RT alone (46.3% vs 23.4%; P = .02) as was 1-year PFS (17.9% vs 5.3%; P = .02). No significant difference in 1-year OS (73.2% vs 64.4%; P = .23) or 1-year PFS (44.5% vs 44.3%; P = .33) between DE-RT + TMZ and SoC-RT + TMZ was noted. No difference in 1-year OS was noted between DE-RT + TMZ and SoC-RT + TMZ in either MGMT methylated (83.2% vs 73.2%; P = .23) or MGMT unmethylated (72.6% vs 50.6%; P = .16) patients.
CONCLUSIONS
DE-RT alone resulted in superior PFS and OS versus SoC-RT alone. DE-RT + TMZ did not lead to improved outcomes versus SoC-RT + TMZ. No differential benefit based on MGMT status was found. Future studies are warranted to define which subgroups benefit most from DE-RT.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain Neoplasms; Child; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Middle Aged; Prospective Studies; Radiotherapy Dosage; Standard of Care; Temozolomide; Tumor Suppressor Proteins; Young Adult
PubMed: 33991621
DOI: 10.1016/j.ijrobp.2021.05.001 -
Radiation Oncology (London, England) Mar 2024Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival...
PURPOSE/OBJECTIVE(S)
Treatment related lymphopenia is a known toxicity for glioblastoma (GBM) patients and several single-institution studies have linked lymphopenia with poor survival outcomes. We performed a systematic review and pooled analysis to evaluate the association between lymphopenia and overall survival (OS) for GBM patients undergoing chemotherapy and radiation therapy (RT).
MATERIALS/METHODS
Following PRISMA guidelines, a systematic literature review of the MEDLINE database and abstracts from ASTRO, ASCO, and SNO annual meetings was conducted. A pooled analysis was performed using inverse variance-weighted random effects to generate a pooled estimate of the hazard ratio of association between lymphopenia and OS.
RESULTS
Ten of 104 identified studies met inclusion criteria, representing 1,718 patients. The lymphopenia cutoff value varied (400-1100 cells/uL) and as well as the timing of its onset. Studies were grouped as time-point (i.e., lymphopenia at approximately 2-months post-RT) or time-range (any lymphopenia occurrence from treatment-start to approximately 2-months post-RT. The mean overall pooled incidence of lymphopenia for all studies was 31.8%, and 11.8% vs. 39.9% for time-point vs. time-range studies, respectively. Lymphopenia was associated with increased risk of death, with a pooled HR of 1.78 (95% CI 1.46-2.17, P < 0.00001) for the time-point studies, and a pooled HR of 1.38 (95% CI 1.24-1.55, P < 0.00001) for the time-point studies. There was no significant heterogeneity between studies.
CONCLUSION
These results strengthen observations from previous individual single-institution studies and better defines the magnitude of the association between lymphopenia with OS in GBM patients, highlighting lymphopenia as a poor prognostic factor.
Topics: Humans; Glioblastoma; Temozolomide; Brain Neoplasms; Lymphopenia
PubMed: 38481255
DOI: 10.1186/s13014-023-02393-3 -
Advanced Drug Delivery Reviews Jan 2020Skin cancer is a high burden disease with a high impact on global health. Conventional therapies have several drawbacks; thus, the development of effective therapies is...
Skin cancer is a high burden disease with a high impact on global health. Conventional therapies have several drawbacks; thus, the development of effective therapies is required. In this context, nanotechnology approaches are an attractive strategy for cancer therapy because they enable the efficient delivery of drugs and other bioactive molecules to target tissues with low toxic effects. In this review, nanotechnological tools for skin cancer will be summarized and discussed. First, pathology and conventional therapies will be presented, followed by the challenges of skin cancer therapy. Then, the main features of developing efficient nanosystems will be discussed, and next, the most commonly used nanoparticles (NPs) described in the literature for skin cancer therapy will be presented. Subsequently, the use of NPs to deliver chemotherapeutics, immune and vaccine molecules and nucleic acids will be reviewed and discussed as will the combination of physical methods and NPs. Finally, multifunctional delivery systems to codeliver anticancer therapeutic agents containing or not surface functionalization will be summarized.
Topics: Administration, Cutaneous; Antineoplastic Agents; Dacarbazine; Drug Carriers; Drug Resistance, Neoplasm; Fluorouracil; Gold; Humans; Melanoma; Metal Nanoparticles; Nanoparticles; Nanotechnology; Particle Size; Skin Absorption; Skin Neoplasms; Skin Physiological Phenomena; Surface Properties
PubMed: 32113956
DOI: 10.1016/j.addr.2020.02.005 -
Clinical & Translational Oncology :... Jun 2021Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive...
PURPOSE
Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive function is a major issue and its effects in young males are largely neglected by novel research. To improve clinician awareness, we systematically reviewed side effects of chemotherapy for Hodgkin lymphoma (HL) in young males.
METHODS
The review was prospectively registered (PROSPERO N. CRD42019122868). Three databases (Medline via PUBMED, SCOPUS, and Cochrane Library) were searched for studies featuring males aged 13-51-years who underwent chemotherapy for HL using ABVD (Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine) or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) regimens. These chemotherapy regimens were compared against each other using sperm characteristics, FSH, and inhibin B levels to measure fertility levels.
RESULTS
Data were extracted from five studies featuring 1344 patients. 6 months post-ABVD saw marked deterioration in sperm count, further reduced by more cycles (P = 0.05). Patients treated with BEACOPP rather than ABVD were more prone to oligospermia. Receiving fewer cycles of both regimens increased the likelihood of sperm production recovering. Patients treated with 6-8 cycles of BEACOPP did not recover spermiogenesis.
CONCLUSIONS
ABVD and BEACOPP regimens significantly reduce fertility function to varying effects depending on treatment duration. ABVD temporarily causes significant reductions in male fertility, whereas BEACOPP's effects are more permanent. Therefore, clinicians should discuss fertility preservation with male patients receiving infertility-inducing gonadotoxic therapy. Further high-quality studies are required to more adequality describe the risk to fertility by chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Fertility; Hodgkin Disease; Humans; Infertility, Male; Male; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 32944834
DOI: 10.1007/s12094-020-02483-8