scholarly journals Mapping the preclinical to clinical evidence and development trajectory of the oncolytic virus talimogene laherparepvec (T-VEC): a systematic review

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e029475 ◽  
Author(s):  
Manoj Lalu ◽  
Garvin J Leung ◽  
Yuan Yi Dong ◽  
Joshua Montroy ◽  
Claire Butler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Studies ◽  
Clinical Evidence ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Risk Of Bias ◽  
Preclinical Studies ◽  
Talimogene Laherparepvec ◽  
Development Trajectory

ObjectiveThis study aimed to conduct a systematic review of preclinical and clinical evidence to chart the successful trajectory of talimogene laherparepvec (T-VEC) from the bench to the clinic.DesignThis study was a systematic review. The primary outcome of interest was the efficacy of treatment, determined by complete response. Abstract and full-text selection as well as data extraction were done by two independent reviewers. The Cochrane risk of bias tool was used to assess the risk of bias in studies.SettingEmbase, Embase Classic and OvidMedline were searched from inception until May 2016 to assess its development trajectory to approval in 2015.ParticipantsPreclinical and clinical controlled comparison studies, as well as observational studies.InterventionsT-VEC for the treatment of any malignancy.Results8852 records were screened and five preclinical (n=150 animals) and seven clinical studies (n=589 patients) were included. We saw large decreases in T-VEC’s efficacy as studies moved from the laboratory to patients, and as studies became more methodologically rigorous. Preclinical studies reported complete regression rates up to 100% for injected tumours and 80% for contralateral tumours, while the highest degree of efficacy seen in the clinical setting was a 24% complete response rate, with one study experiencing a complete response rate of 0%. We were unable to reliably assess safety due to the lack of reporting, as well as the heterogeneity seen in adverse event definitions. All preclinical studies had high or unclear risk of bias, and all clinical studies were at a high risk of bias in at least one domain.ConclusionsOur findings illustrate that even successful biotherapeutics may not demonstrate a clear translational road map. This emphasises the need to consider increasing rigour and transparency along the translational pathway.PROSPERO registration numberCRD42016043541.

scholarly journals Response and relapse rates after treatment with long-acting somatostatin analogs in multifocal or recurrent type-1 gastric carcinoids: A systematic review and meta-analysis

2019 ◽  
Vol 8 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Roberta Elisa Rossi ◽  
Pietro Invernizzi ◽  
Vincenzo Mazzaferro ◽  
Sara Massironi
Keyword(s):  
Systematic Review ◽  
Neuroendocrine Tumors ◽  
Response Rate ◽  
Complete Response Rate ◽  
Somatostatin Analogs ◽  
Complete Response ◽  
Long Acting ◽  
Cumulative Relapse Rate

Background Type-1 gastric neuroendocrine tumors represent a recurring disease and long-acting somatostatin analogs can inhibit both gastrin release and endocrine cell proliferation. The efficacy and timing of this treatment are still unclear. We performed a systematic review of the literature to clarify the role of somatostatin analog treatment in type-1 gastric neuroendocrine tumors. Methods A computerized literature search was performed using relevant keywords to identify all the pertinent articles published in the last 15 years. Results Eight studies were included in this systematic review on somatostatin analogs in type-1 gastric neuroendocrine tumors. A complete response rate ranged from 25–100%. When only the six prospective studies were considered, no significant heterogeneity was observed, and the pooled cumulative complete response rate was 84.5% (confidence interval 73.8–92.8). Three studies evaluated the type-1 gastric neuroendocrine tumor recurrence, with a cumulative relapse rate of 30.2% (confidence interval 13.1–50.6) after 34 months. Conclusion Somatostatin analogs, namely lanreotide and octreotide, have an excellent response rate, with a good safety profile in selected type-1 gastric neuroendocrine tumors, which cannot be safely managed by endoscopic follow-up or resection due to multiple or frequently recurring disease. After therapy discontinuation, the cumulative relapse rate observed after a median 34-month follow-up was relatively high (30.2%).

Efficacy of Photodynamic Therapy for the Treatment of Bowen’s Disease: A Meta-Analysis of Randomized Controlled Trials

Dermatology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Wen-Li Xue ◽  
Jia-Qi Ruan ◽  
Hong-Ye Liu ◽  
Hong-Xia He
Keyword(s):  
Photodynamic Therapy ◽  
Response Rate ◽  
Complete Response Rate ◽  
Meta Analysis ◽  
Complete Response ◽  
Risk Of Bias ◽  
Bowen’S Disease ◽  
Bowen's Disease ◽  
Randomized Controlled ◽  
Significant Difference

<b><i>Background:</i></b> Photodynamic therapy is an established treatment option for Bowen’s disease. Our meta-analysis was aimed at evaluating the efficacy and recurrence of photodynamic therapy or other topical treatments (5-fluorouracil, cryotherapy) and of photodynamic therapy alone or in combination with other therapies (ablative fractional CO<sub>2</sub> laser or plum-blossom needle) for the treatment of Bowen’s disease. <b><i>Methods:</i></b> Trials that met our inclusion criteria were identified from PubMed, EMBASE, Web of Science, and Cochrane Library databases, and meta-analyses were conducted with RevMan V.5.4. The risk of bias was estimated with the Cochrane Collaboration’s risk of bias tools. Complete response rate, recurrence, pain/visual analogue scale score, cosmetic outcome, and adverse events were considered as outcomes. <b><i>Results:</i></b> Of the 2,439 records initially retrieved, 8 randomized controlled trials were included in this meta-analysis. According to our analyses, photodynamic therapy exhibited a significantly higher complete response rate (RR = 1.36, 95% CI [1.01, 1.84], <i>I</i><sup>2</sup> = 86%, <i>p</i> = 0.04), less recurrence (RR = 0.53, 95% CI [0.30, 0.95], <i>I</i><sup>2</sup> = 0%, <i>p</i> = 0.03), and better cosmetic outcome (RR = 1.34, 95% CI [1.15, 1.56], <i>I</i><sup>2</sup> = 0%, <i>p</i> = 0.0002) compared with other treatments. Moreover, there was a significant difference between the complete response rate of photodynamic therapy combined with ablative fractional CO<sub>2</sub> laser and that of photodynamic therapy (RR = 1.85, 95% CI [1.38, 2.49], <i>I</i><sup>2</sup> = 0%, <i>p</i> &#x3c; 0.0001). Photodynamic therapy combined with ablative fractional CO<sub>2</sub> laser or plum-blossom needle also showed significantly less recurrence (RR = 0.21, 95% CI [0.09, 0.51], <i>I</i><sup>2</sup> = 0%, <i>p</i> = 0.0005) and a lower visual analogue scale score (RR = 0.51, 95% CI [0.06, 0.96], <i>I</i><sup>2</sup> = 0%, <i>p</i> = 0.03) than photodynamic therapy alone. However, there was no significant difference in the complete response rate between photodynamic therapy combined with ablative continuous CO<sub>2</sub> laser and photodynamic therapy combined with ablative fractional CO<sub>2</sub> laser (RR = 1.00, 95% CI [0.54, 1.86], <i>I</i><sup>2</sup> not applicable, <i>p</i> = 1.00). <b><i>Conclusions:</i></b> This meta-analysis shows that photodynamic therapy can be used in the treatment of Bowen’s disease with better efficacy, less recurrence, and better cosmetic outcomes than cryotherapy and 5-FU. Some methods, including ablative fractional CO<sub>2</sub> laser, can be applied in combination with photodynamic therapy to improve efficacy. However, which laser-assisted photodynamic therapy scheme has the most advantages in the treatment of Bowen’s disease warrants further exploration.

scholarly journals Inhibition of Androgen Signalling Improves the Outcomes of Therapies for Bladder Cancer: Results from a Systematic Review of Preclinical and Clinical Evidence and Meta-Analysis of Clinical Studies

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 351
Author(s):  
Massimiliano Creta ◽  
Giuseppe Celentano ◽  
Luigi Napolitano ◽  
Roberto La Rocca ◽  
Marco Capece ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
Relative Risk ◽  
Clinical Studies ◽  
Clinical Evidence ◽  
Meta Analysis ◽  
Bladder Tumour ◽  
Signalling Pathways ◽  
Reductase Inhibitors ◽  
The Impact

Bladder cancer (BCa) is an endocrine-related tumour and the activation of androgen signalling pathways may promote bladder tumorigenesis. We summarized the available preclinical and clinical evidence on the implications of the manipulation of androgen signalling pathways on the outcomes of BCa therapies. A systematic review was performed in December 2020. We included papers that met the following criteria: original preclinical and clinical research; evaluating the impact of androgen signalling modulation on the outcomes of BCa therapies. Six preclinical and eight clinical studies were identified. The preclinical evidence demonstrates that the modulation of androgen receptor-related pathways has the potential to interfere with the activity of the Bacillus Calmette Guerin, doxorubicin, cisplatin, gemcitabine, and radiotherapy. The relative risk of BCa recurrence after transurethral resection of the bladder tumour (TURBT) is significantly lower in patients undergoing therapy with 5 alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT) (Relative risk: 0.50, 95% CI: 0.30–0.82; p = 0.006). Subgroup analysis in patients receiving 5-ARIs revealed a relative risk of BCa recurrence of 0.46 (95% CI: 0.22–0.95; p = 0.040). A significant negative association between the ratio of T1 BCa patients in treated/control groups and the relative risk of BCa recurrence was observed. Therapy with 5-ARIs may represent a potential strategy aimed at reducing BCa recurrence rate, mainly in patients with low stage disease. Further studies are needed to confirm these preliminary data.

scholarly journals Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

2018 ◽  
Vol 29 (3) ◽  
pp. 321-332 ◽  
Author(s):  
Suleiman Alhaji Muhammad ◽  
Norshariza Nordin ◽  
Sharida Fakurazi
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Animal Models ◽  
Conditioned Medium ◽  
Tissue Regeneration ◽  
Therapeutic Benefit ◽  
Risk Of Bias ◽  
Preclinical Studies

AbstractInjury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium inin vivoanimal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials.

Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

scholarly journals Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy

Oncotarget ◽  
2018 ◽  
Vol 9 (41) ◽  
pp. 26406-26416 ◽  
Author(s):  
Angela Santonja ◽  
Alfonso Sánchez-Muñoz ◽  
Ana Lluch ◽  
Maria Rosario Chica-Parrado ◽  
Joan Albanell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Response Rate ◽  
Complete Response Rate ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Cancer Subtypes ◽  
Pathologic Complete Response Rate

The Effect of Plantago major on Wound Healing in Preclinical Studies: A Systematic Review

2021 ◽  
Vol 67 (1) ◽  
pp. 27-34
Author(s):  
Fernanda Cardoso ◽  
Jéssica Breder ◽  
Priscila Apolinário ◽  
Henrique Oliveia ◽  
Maria Saidel ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Risk Of Bias ◽  
Preclinical Studies ◽  
Plantago Major ◽  
Best Response ◽  
Meta Analyses

BACKGROUND: Plantago major is a medicinal plant that has been used for centuries to treat various health conditions including wounds. PURPOSE: To investigate the effectiveness of the topical use of P major in healing skin wounds in animal models. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review was conducted. Seven (7) electronic databases (Virtual Health Library, Public/Publisher MEDLINE, Scopus, Web of Science, Embase, Cumulative Index of Nursing and Allied Health Literature, and CAB Direct) were searched for controlled studies published in English from January 2006 to March 2020. The Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies tools guided the evaluation of the studies and determined their quality. The Systematic Review Center for Laboratory Animal Experimentation was used to assess the risk of bias. RESULTS: Of the 176 publications identified, 4 met the inclusion criteria. Studies included 20 to 100 animals and varying concentrations of P major. There were no reports of losses during research. Wound healing was assessed between 17 and 21 days following wounding. The best response in terms of wound contraction rate occurred with 10%, 20%, and 50% concentrations when compared with control groups. One (1) study did not have an animal ethics committee review. All studies had a high risk of bias and a lack of methodological rigor. CONCLUSION: The results of this review did not find evidence about the in vivo effectiveness of P major for wound healing. More rigorous preclinical studies with adequate sample sizes are required to identify the best concentrations and formulations as well as increase understanding about the mechanisms of action of P major in wound healing.

Is Childhood General Anesthesia Exposure An Etiological Contributor to Cognitive Impairment?

2021 ◽  
Vol 36 (3) ◽  
pp. 251-259
Author(s):  
Yi Tian ◽  
Peiyu Liu ◽  
Weisong Liu ◽  
Qiaojing Xu ◽  
Xiangkun Zhao
Keyword(s):  
Risk Factors ◽  
Early Childhood ◽  
Cognitive Impairment ◽  
General Anesthesia ◽  
Strong Correlation ◽  
Clinical Studies ◽  
Clinical Evidence ◽  
Preclinical Studies ◽  
Invasive Procedures ◽  
Immature Brain

General anesthesia is necessary for patients to undergo surgery and invasive procedures. However, numerous preclinical studies have demonstrated widespread developmental neurotoxicity of the commonly used anesthetics and sedatives for the immature brain. Clinical studies also suggest a strong correlation between childhood anesthesia exposure and subsequent behavioral or cognitive impairment in adulthood. These findings have attracted increasing attention of anesthesiologists, pediatricians, and caregivers about the safety of anesthesia exposure in children, especially during early childhood. Herein, the aim of this review was to present the molecular mechanism of general anesthesia and its effects on the developing brain and introduce the recent clinical evidence of changes in cognition function post-childhood general anesthesia exposure. More importantly, some of the spots will be importantly discussed to scrutinize the phenomena; only in this way, it may help minimize or eliminate relevant risk factors.

Sign in / Sign up

Export Citation Format

Share Document