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Pharmacological Research Sep 2021Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature,...
Glioblastoma multiforme (GBM) is a WHO grade IV glioma and the most common malignant, primary brain tumor with a 5-year survival of 7.2%. Its highly infiltrative nature, genetic heterogeneity, and protection by the blood brain barrier (BBB) have posed great treatment challenges. The standard treatment for GBMs is surgical resection followed by chemoradiotherapy. The robust DNA repair and self-renewing capabilities of glioblastoma cells and glioma initiating cells (GICs), respectively, promote resistance against all current treatment modalities. Thus, durable GBM management will require the invention of innovative treatment strategies. In this review, we will describe biological and molecular targets for GBM therapy, the current status of pharmacologic therapy, prominent mechanisms of resistance, and new treatment approaches. To date, medical imaging is primarily used to determine the location, size and macroscopic morphology of GBM before, during, and after therapy. In the future, molecular and cellular imaging approaches will more dynamically monitor the expression of molecular targets and/or immune responses in the tumor, thereby enabling more immediate adaptation of tumor-tailored, targeted therapies.
Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Drug Resistance, Neoplasm; Glioblastoma; Humans
PubMed: 34302977
DOI: 10.1016/j.phrs.2021.105780 -
Current Pain and Headache Reports May 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and often painful condition that occurs after administration of chemotherapeutic agents. The primary... (Review)
Review
PURPOSE OF REVIEW
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and often painful condition that occurs after administration of chemotherapeutic agents. The primary objective of this systematic review was to appraise the literature on conservative, pharmacological, and interventional treatment options for CIPN pain.
RECENT FINDINGS
There is level I evidence supporting modest to moderate improvement in CIPN pain from duloxetine treatment, as well as short-term modest improvement from physical therapy and acupuncture. Although opioid and cannabis administration may provide short-term modest improvement, administration is commonly limited by side effects. Generally, most studies reported no clinical benefit from yoga, topical neuropathic agents, gabapentinoids, and tricyclic antidepressants. Evidence is currently equivocal for scrambler therapy and transcutaneous electrical nerve stimulation. Finally, evidence on neuromodulation options is limited to mostly case reports/series and one observational study highlighting moderate improvement with auricular nerve stimulation. This systematic review provides an overview of conservative, pharmacologic, and interventional treatment modalities for CIPN pain. Furthermore, it provides a level of evidence and degree of recommendation based on the United States Preventive Services Task Force (USPSTF) criteria for each specific treatment modality.
Topics: Humans; Neuralgia; Neoplasms; Antineoplastic Agents; Pain Management; Transcutaneous Electric Nerve Stimulation; Observational Studies as Topic
PubMed: 37058254
DOI: 10.1007/s11916-023-01107-4 -
Critical Reviews in Oncology/hematology Mar 2022Pharmacological strategies for chemotherapy-induced peripheral neurotoxicity (CIPN) are very limited. We systematically reviewed data on rehabilitation, exercise,... (Review)
Review
Rehabilitation, exercise, and related non-pharmacological interventions for chemotherapy-induced peripheral neurotoxicity: Systematic review and evidence-based recommendations.
Pharmacological strategies for chemotherapy-induced peripheral neurotoxicity (CIPN) are very limited. We systematically reviewed data on rehabilitation, exercise, physical therapy, and other physical non-pharmacological interventions and offered evidence-based recommendations for the prevention and treatment of CIPN. A literature search using PubMed, Web of Science and CINAHL was conducted from database inception until May 31st, 2021. 2791 records were title-abstract screened, 71 papers were full-text screened, 41 studies were included, 21 on prevention and 20 on treatment of CIPN. Treatment type, cancer type, chemotherapy compounds were heterogeneous, sample size was small (median: N = 34) and intention-to-treat analysis was lacking in 26/41 reports. Because of the methodological issues of included studies, the reviewed evidence should be considered as preliminary. Exercise, endurance, strength, balance, and sensorimotor training have been studied in low-to-moderate quality studies, while the evidence for other treatments is preliminary/inconclusive. We offer recommendation for the design of future trials on CIPN.
Topics: Antineoplastic Agents; Exercise; Humans; Neoplasms; Peripheral Nervous System Diseases
PubMed: 34968623
DOI: 10.1016/j.critrevonc.2021.103575 -
Cancer Treatment Reviews Jul 2023Antibody drug conjugates (ADCs) represent a revolutionary drug class in cancer therapy, combining the precision of targeted therapy with the cytotoxic effects of... (Review)
Review
BACKGROUND
Antibody drug conjugates (ADCs) represent a revolutionary drug class in cancer therapy, combining the precision of targeted therapy with the cytotoxic effects of chemotherapy. Promising activity of novel ADCs, namely Trastuzumab Deruxtecan and Patritumab Deruxtecan, has been observed in hard-to treat molecular subtypes, such as HER2-positive and heavily pretreated EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). However, therapeutic advances are expected in certain subgroups of lung cancer patients, including non-oncogene-addicted NSCLC after failure of current standard of care (e.g., immunotherapy with or without chemotherapy, chemo-antiangiogenic treatment). Trophoblastic Cell Surface Antigen 2 (TROP-2) is a surface transmembrane glycoprotein member of the epithelial cell adhesion molecule (EpCAM) family. TROP-2 represents a promising therapeutic target in refractory non-oncogene-addicted NSCLC.
METHODOLOGY
We performed a systematic literature search of the clinical trials about TROP-2 directed ADCs in NSCLC referenced in the pubmed.gov database, Cochrane Library database and clinicaltrial.gov database.
RESULTS
First-in-humans ADCs targeting TROP-2, namely Sacituzumab Govitecan (SN-38) and Datopotamab Deruxtecan (Dxd), yielded promising activity signals in NSCLC with a manageable safety profile. Most common grade ≥ 3 adverse events (AEs) of Sacituzumab Govitecan included neutropenia (28 %), diarrhea (7 %), nausea (7 %), fatigue (6 %), and febrile neutropenia (4 %). Nausea and stomatitis were the most common all grade AEs with Datopotamab Deruxtecan; dyspnea, amylase increase, hyperglycemia and lymphopenia were reported as grade ≥ 3 AEs in less than 12 % of patients.
CONCLUSION
As more effective strategies are needed for patients with refractory non-oncogene-addicted NSCLC, the design of novel clinical trials with ADCs targeting TROP-2 is encouraged as both a monotherapy or combination strategy with existing agents (e.g., monoclonal antibodies targeting immune checkpoint inhibitors or chemotherapy).
Topics: Humans; Antineoplastic Agents; Camptothecin; Carcinoma, Non-Small-Cell Lung; Immunoconjugates; Irinotecan; Lung Neoplasms
PubMed: 37230055
DOI: 10.1016/j.ctrv.2023.102572 -
Intermittent Fasting in Breast Cancer: A Systematic Review and Critical Update of Available Studies.Nutrients Jan 2023Breast cancer (BC) is the most-frequent malignancy amongst women, whereas obesity and excess caloric consumption increase the risk for developing the disease. The... (Review)
Review
Breast cancer (BC) is the most-frequent malignancy amongst women, whereas obesity and excess caloric consumption increase the risk for developing the disease. The objective of this systematic review was to examine the impact of intermittent fasting (IF) on previously diagnosed BC patients, regarding quality of life (QoL) scores during chemotherapy, chemotherapy-induced toxicity, radiological response and BC recurrence, endocrine-related outcomes, as well as IF-induced adverse effects in these populations. A comprehensive search was conducted between 31 December 2010 and 31 October 2022, using the PubMed, CINAHL, Cochrane, Web of Science, and Scopus databases. Two investigators independently performed abstract screenings, full-text screenings, and data extraction, and the Mixed Method Appraisal Tool (MMAT) was used to evaluate the quality of the selected studies. We screened 468 papers, 10 of which were selected for data synthesis. All patients were female adults whose age ranged between 27 and 78 years. Participants in all studies were women diagnosed with BC of one of the following stages: I, II (HER2-/+), III (HER2-/+), IV, LUMINAL-A, LUMINAL-B (HER2-/+). Notably, IF during chemotherapy was found to be feasible, safe and able to relieve chemotherapy-induced adverse effects and cytotoxicity. IF seemed to improve QoL during chemotherapy, through the reduction of fatigue, nausea and headaches, however data were characterized as low quality. IF was found to reduce chemotherapy-induced DNA damage and augmented optimal glycemic regulation, improving serum glucose, insulin, and IGF-1 concentrations. A remarkable heterogeneity of duration of dietary patterns was observed among available studies. In conclusion, we failed to identify any IF-related beneficial effects on the QoL, response after chemotherapy or related symptoms, as well as measures of tumor recurrence in BC patients. We identified a potential beneficial effect of IF on chemotherapy-induced toxicity, based on markers of DNA and leukocyte damage; however, these results were derived from three studies and require further validation. Further studies with appropriate design and larger sample sizes are warranted to elucidate its potential standard incorporation in daily clinical practice.
Topics: Adult; Aged; Female; Humans; Middle Aged; Antineoplastic Agents; Breast Neoplasms; Intermittent Fasting; Neoplasm Recurrence, Local; Quality of Life
PubMed: 36771239
DOI: 10.3390/nu15030532 -
In Vivo (Athens, Greece) 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment, resulting in pain, numbness, instability, and thus affecting quality of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIM
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment, resulting in pain, numbness, instability, and thus affecting quality of life (QoL), occasionally leading to discontinuation of chemotherapy. Pharmacological treatments are not sufficient. Non-pharmacological interventions (NPIs) have also been tried. This study aimed to systematically review the efficacy of NPIs on pain and QoL in patients suffering from CIPN.
MATERIALS AND METHODS
The databases searched were Pubmed, Cohrane, and Scopus for randomized controlled trials (RCTs) published in the last 5 years (2017-2022). Studies were considered eligible, if they assessed adult patients suffering from CIPN because of any chemotherapeutic drug for any type and any stage of cancer and if study protocols included non-pharmacological intervention with a structured protocol.
RESULTS
A total of 1,496 records were identified. Finally, 10 RCTs including 495 patients (253 in the intervention group and 242 in the control group) were included for meta-analysis. Intervention protocols included acupuncture (n=6), exercise (n=3), and yoga (n=1). NPIs significantly reduced neuropathic pain. However, the effect on QoL was not significant.
CONCLUSION
NPIs are beneficial in the treatment of pain in patients with CIPN but their impact on QoL is not statistically supported. Larger sample sizes, more homogenous in outcome measures and interventions are needed to further explore NPIs' efficacy on CIPN symptoms.
Topics: Adult; Humans; Antineoplastic Agents; Neoplasms; Polyneuropathies; Neuralgia; Quality of Life
PubMed: 36593011
DOI: 10.21873/invivo.13053 -
Archives of Physical Medicine and... Nov 2022This systematic review analyzed the effects of physical exercise programs in patients with cancer undergoing chemotherapy on chemotherapy-induced peripheral neuropathy... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review analyzed the effects of physical exercise programs in patients with cancer undergoing chemotherapy on chemotherapy-induced peripheral neuropathy (CIPN) prevention.
DATA SOURCES
PubMed, Web of Science, Scopus, and Cochrane Library were searched for relevant studies published before December 2020. Additional references were identified by manual screening of the reference lists.
STUDY SELECTION
Based on the Population, Intervention, Comparator, Outcomes, and Study Designs strategy, randomized controlled trials in which physical exercise was applied before or during chemotherapy to prevent or ameliorate CIPN were included.
DATA EXTRACTION
Two reviewers blinded and independent screened the articles, scored methodologic quality, and extracted data for analysis. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Sensitivity and precision analysis databases was included. Risk of bias assessment and meta-analysis were conducted using the Cochrane tools.
DATA SYNTHESIS
Of 229 potentially relevant studies, 8 randomized controlled trials were included and scored. They comprise a total of 618 patients with cancer. MEDLINE and Scopus databases recorded the highest sensitivity. None of the studies achieved a "low" overall risk of bias. Four studies were included in meta-analysis for quality of life, and a significance standardized mean difference was found between groups from baseline of 14.62; 95% CI, 6.03-3.20, with a large effect size g=0.83; 95% CI, 0.48-1.18) in favor of physical exercise program compared with usual care.
CONCLUSIONS
Physical exercise at the onset of chemotherapy has shown promising effects on the prevention of CIPN, specially improving quality of life.
Topics: Humans; Quality of Life; Exercise; Neoplasms; Peripheral Nervous System Diseases; Antineoplastic Agents
PubMed: 35271844
DOI: 10.1016/j.apmr.2022.02.008 -
Medical Sciences (Basel, Switzerland) Jan 2023Most individuals affected by cancer who are treated with certain chemotherapies suffer of CIPN. Therefore, there is a high patient and provider interest in... (Review)
Review
Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy (CIPN) with Non-Pharmacological Interventions: Clinical Recommendations from a Systematic Scoping Review and an Expert Consensus Process.
Most individuals affected by cancer who are treated with certain chemotherapies suffer of CIPN. Therefore, there is a high patient and provider interest in complementary non-pharmacological therapies, but its evidence base has not yet been clearly pointed out in the context of CIPN. The results of a scoping review overviewing the published clinical evidence on the application of complementary therapies for improving the complex CIPN symptomatology are synthesized with the recommendations of an expert consensus process aiming to draw attention to supportive strategies for CIPN. The scoping review, registered at PROSPERO 2020 (CRD 42020165851), followed the PRISMA-ScR and JBI guidelines. Relevant studies published in Pubmed/MEDLINE, PsycINFO, PEDro, Cochrane CENTRAL, and CINAHL between 2000 and 2021 were included. CASP was used to evaluate the methodologic quality of the studies. Seventy-five studies with mixed study quality met the inclusion criteria. Manipulative therapies (including massage, reflexology, therapeutic touch), rhythmical embrocations, movement and mind-body therapies, acupuncture/acupressure, and TENS/Scrambler therapy were the most frequently analyzed in research and may be effective treatment options for CIPN. The expert panel approved 17 supportive interventions, most of them were phytotherapeutic interventions including external applications and cryotherapy, hydrotherapy, and tactile stimulation. More than two-thirds of the consented interventions were rated with moderate to high perceived clinical effectiveness in therapeutic use. The evidence of both the review and the expert panel supports a variety of complementary procedures regarding the supportive treatment of CIPN; however, the application on patients should be individually weighed in each case. Based on this meta-synthesis, interprofessional healthcare teams may open up a dialogue with patients interested in non-pharmacological treatment options to tailor complementary counselling and treatments to their needs.
Topics: Humans; Antineoplastic Agents; Consensus; Peripheral Nervous System Diseases; Neoplasms; Complementary Therapies
PubMed: 36810482
DOI: 10.3390/medsci11010015 -
Medicine Apr 2021In recent years, immune checkpoint inhibitors (ICIs) including atezolizumab, durvalumab, pembrolizumab, and nivolumab have reported their efficacy and safety profile in... (Meta-Analysis)
Meta-Analysis
Comparison of atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with extensive-stage small cell lung cancer: A systematic review and network meta-analysis.
BACKGROUND
In recent years, immune checkpoint inhibitors (ICIs) including atezolizumab, durvalumab, pembrolizumab, and nivolumab have reported their efficacy and safety profile in patients with extensive-stage small cell lung cancer (ES-SCLC). However, given the diverse efficacy and inconsistent safety among the ICIs, with the absence of head-to-head researches designed to evaluate the efficacy among them, it might bring with confusion on selection in clinical practice.
OBJECTIVES
The present systematic review and network meta-analysis was performed to conduct indirect comparisons on efficacy and safety profile among ICIs, including atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with ES-SCLC.
DESIGN
Several databases were retrieved with established criteria until June 20, 2020, with the main MeSH Terms and their similarities. Hazard ratios of overall survival (OS) and progression-free survival (PFS), odds ratios (ORs) of disease control rate (DCR), objective response rate (ORR), and adverse events (AEs) were compared indirectly with network meta-analysis.
DATA SOURCES
Medline, Cochrane library, and Embase.
ELIGIBILITY CRITERIA
Prospective, randomized, controlled clinical studies, which reported PFS, OS, and AEs.
DATA EXTRACTION AND SYNTHESIS
Clinical characteristics were extracted by the 2 authors independently. Comparisons of HRs were calculated for PFS and OS by random effect model. ORR, DCR, and AEs were presented with ORs. Based on surface under the cumulative ranking curve, and forest plots, efficacy and safety of the treatments were ranked, with predicted histogram described.
RESULTS
In total, there were 4 studies including 1547 patients who met the eligibility criteria and enrolled. For indirect comparisons, no significant difference on PFS was observed between atezolizumab and durvalumab (HR 0.96, 95% CI, 0.72-1.29), or between atezolizumab and pembrolizumab (HR 1.05, 95% CI, 0.78-1.43), or between atezolizumab and nivolumab (HR 1.18, 95% CI, 0.79-1.79), or between durvalumab and pembrolizumab (HR 1.10, 95% CI, 0.84-1.43). or between durvalumab and nivolumab (HR 1.23, 95% CI, 0.83-1.82), or between pembrolizumab and nivolumab (HR 1.12, 95% CI, 0.76-1.66), nor significant difference on OS observed between atezolizumab and durvalumab (HR 0.93, 95% CI, 0.67-1.30), or between atezolizumab and pembrolizumab (HR 0.88, 95% CI, 0.62-1.24), or between atezolizumab and nivolumab (HR 1.04, 95% CI, 0.66-1.66), or between durvalumab and pembrolizumab (HR 0.94, 95% CI, 0.70-1.25), or between durvalumab and nivolumab (HR 1.12, 95% CI, 0.73-1.71), or between pembrolizumab and nivolumab (HR 1.19, 95% CI, 0.77-1.84). However, durvalumab was shown statistical superiority on ORR when compared with atezolizumab (HR 0.79, 95% CI, 0.64-0.98), also with significantly higher risk on immune-related AEs when compared with atezolizumab (OR 0.22, 95% CI, 0.10-0.50), and pembrolizumab (OR 3.12, 95% CI, 1.27-7.64).
CONCLUSIONS
Results of the study revealed that there was no statistical difference on PFS or OS among agents of atezolizumab, durvalumab, pembrolizumab, and nivolumab as first-line treatment in patients with ES-SCLC. However, durvalumab was shown superiority on ORR when compared with atezolizumab, also with significantly higher risk on immune-related AEs.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Humans; Lung Neoplasms; Neoplasm Staging; Network Meta-Analysis; Nivolumab; Progression-Free Survival; Randomized Controlled Trials as Topic; Small Cell Lung Carcinoma
PubMed: 33847617
DOI: 10.1097/MD.0000000000025180 -
Archives of Disease in Childhood Feb 2022To assess the efficacy of oral low-level laser therapy (LLLT) - also known as photobiomodulation - in the reduction of oral mucositis experienced by children and young...
OBJECTIVE
To assess the efficacy of oral low-level laser therapy (LLLT) - also known as photobiomodulation - in the reduction of oral mucositis experienced by children and young people with cancer undergoing chemotherapy.
DESIGN
A systematic review to evaluate the efficacy of oral LLLT for oral mucositis in children with cancer and the safety of oral LLLT in any age with cancer (International Prospective Register of Systematic Reviews/PROSPERO registration: CRD42018099772). Multiple databases and grey literature were screened. Randomised controlled trials were considered for assessing efficacy, and all studies were considered for assessing safety. Primary outcomes included severity of oral mucositis, oral pain and adverse events. Where results were compatible, meta-analysis was performed using a random-effects model. A narrative synthesis considered other outcome measures.
RESULTS
14 studies (n>416 children) were included in the narrative synthesis of LLLT efficacy. 5 studies (n=380 children and young people) were included in the meta-analyses. Results demonstrate that LLLT may reduce the severity of oral mucositis and the level of oral pain, but further randomised controlled trials are needed to confirm or deny this. There is vast variation in different trial protocols. Insufficient blinding between LLLT or sham therapy/control led to a strong risk of performance bias. 75 studies (encompassing 2712 patients of all ages who had undergone LLLT) demonstrated minor and infrequent adverse reactions, but most studies had significant areas of weakness in quality.
CONCLUSION
LLLT appears to be a safe therapy, but further evidence is needed to assess its efficacy as a prevention or treatment tool for oral mucositis in children with cancer.
Topics: Antineoplastic Agents; Child; Humans; Low-Level Light Therapy; Neoplasms; Stomatitis; Treatment Outcome
PubMed: 34230010
DOI: 10.1136/archdischild-2020-321216