Other Experimental Therapies for Glioma

2009 ◽  
pp. 155-164 ◽  
Author(s):  
Manfred Westphal ◽  
Katrin Lamszus
Keyword(s):  
Experimental Therapies

scholarly journals Drug interactions: a review of the unseen danger of experimental COVID-19 therapies

2020 ◽  
Vol 75 (12) ◽  
pp. 3417-3424 ◽  
Author(s):  
Catherine Hodge ◽  
Fiona Marra ◽  
Catia Marzolini ◽  
Alison Boyle ◽  
Sara Gibbons ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Herbal Medicines ◽  
Qt Prolongation ◽  
Critically Ill Patient ◽  
Experimental Drugs ◽  
Mesh Terms ◽  
Experimental Therapies ◽  
Clinically Significant ◽  
Novel Coronavirus

Abstract As global health services respond to the coronavirus pandemic, many prescribers are turning to experimental drugs. This review aims to assess the risk of drug–drug interactions in the severely ill COVID-19 patient. Experimental therapies were identified by searching ClinicalTrials.gov for ‘COVID-19’, ‘2019-nCoV’, ‘2019 novel coronavirus’ and ‘SARS-CoV-2’. The last search was performed on 30 June 2020. Herbal medicines, blood-derived products and in vitro studies were excluded. We identified comorbidities by searching PubMed for the MeSH terms ‘COVID-19’, ‘Comorbidity’ and ‘Epidemiological Factors’. Potential drug–drug interactions were evaluated according to known pharmacokinetics, overlapping toxicities and QT risk. Drug–drug interactions were graded GREEN and YELLOW: no clinically significant interaction; AMBER: caution; RED: serious risk. A total of 2378 records were retrieved from ClinicalTrials.gov, which yielded 249 drugs that met inclusion criteria. Thirteen primary compounds were screened against 512 comedications. A full database of these interactions is available at www.covid19-druginteractions.org. Experimental therapies for COVID-19 present a risk of drug–drug interactions, with lopinavir/ritonavir (10% RED, 41% AMBER; mainly a perpetrator of pharmacokinetic interactions but also risk of QT prolongation particularly when given with concomitant drugs that can prolong QT), chloroquine and hydroxychloroquine (both 7% RED and 27% AMBER, victims of some interactions due to metabolic profile but also perpetrators of QT prolongation) posing the greatest risk. With management, these risks can be mitigated. We have published a drug–drug interaction resource to facilitate medication review for the critically ill patient.

scholarly journals The Importance of Tumor Stem Cells in Glioblastoma Resistance to Therapy

2021 ◽  
Vol 22 (8) ◽  
pp. 3863
Author(s):  
Vincenzo Mattei ◽  
Francesca Santilli ◽  
Stefano Martellucci ◽  
Simona Delle Monache ◽  
Jessica Fabrizi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Radical Surgery ◽  
Cellular Heterogeneity ◽  
Molecular Characteristics ◽  
Tumor Stem Cells ◽  
Current Standard ◽  
New Approach ◽  
Experimental Therapies ◽  
Technical Advances ◽  
New Anticancer Drugs

Glioblastoma (GBM) is known to be the most common and lethal primary malignant brain tumor. Therapies against this neoplasia have a high percentage of failure, associated with the survival of self-renewing glioblastoma stem cells (GSCs), which repopulate treated tumors. In addition, despite new radical surgery protocols and the introduction of new anticancer drugs, protocols for treatment, and technical advances in radiotherapy, no significant improvement in the survival rate for GBMs has been realized. Thus, novel antitarget therapies could be used in conjunction with standard radiochemotherapy approaches. Targeted therapy, indeed, may address specific targets that play an essential role in the proliferation, survival, and invasiveness of GBM cells, including numerous molecules involved in signal transduction pathways. Significant cellular heterogeneity and the hierarchy with GSCs showing a therapy-resistant phenotype could explain tumor recurrence and local invasiveness and, therefore, may be a target for new therapies. Therefore, the forced differentiation of GSCs may be a promising new approach in GBM treatment. This article provides an updated review of the current standard and experimental therapies for GBM, as well as an overview of the molecular characteristics of GSCs, the mechanisms that activate resistance to current treatments, and a new antitumor strategy for treating GSCs for use as therapy.

scholarly journals Recommendations on multiple testing adjustment in multi-arm trials with a shared control group

2016 ◽  
Vol 27 (5) ◽  
pp. 1513-1530 ◽  
Author(s):  
Dena R Howard ◽  
Julia M Brown ◽  
Susan Todd ◽  
Walter M Gregory
Keyword(s):  
False Positive ◽  
Multiple Testing ◽  
Shared Control ◽  
Control Group ◽  
Type I ◽  
False Positive Error ◽  
Control Data ◽  
Experimental Therapies ◽  
Multiple Testing Adjustment ◽  
Independent Trials

Multi-arm clinical trials assessing multiple experimental treatments against a shared control group can offer efficiency advantages over independent trials through assessing an increased number of hypotheses. Published opinion is divided on the requirement for multiple testing adjustment to control the family-wise type-I error rate (FWER). The probability of a false positive error in multi-arm trials compared to equivalent independent trials is affected by the correlation between comparisons due to sharing control data. We demonstrate that this correlation in fact leads to a reduction in the FWER, therefore FWER adjustment is not recommended solely due to sharing control data. In contrast, the correlation increases the probability of multiple false positive outcomes across the hypotheses, although standard FWER adjustment methods do not control for this. A stringent critical value adjustment is proposed to maintain equivalent evidence of superiority in two correlated comparisons to that obtained within independent trials. FWER adjustment is only required if there is an increased chance of making a single claim of effectiveness by testing multiple hypotheses, not due to sharing control data. For competing experimental therapies, the correlation between comparisons can be advantageous as it eliminates bias due to the experimental therapies being compared to different control populations.

Immunological therapy of sepsis: experimental therapies

2001 ◽  
Vol 27 (0) ◽  
pp. S104-S115 ◽  
Author(s):  
Patrick Arndt ◽  
E. Abraham
Keyword(s):  
Immunological Therapy ◽  
Experimental Therapies

scholarly journals Persistent Ependymal Tumor Arising from an Immature Ovarian Teratoma: A Rare Case

2020 ◽  
Author(s):  
Anoshia Afzal ◽  
Rufei Lu ◽  
Sepideh Asadbeigi ◽  
Kar-Ming Fung ◽  
JoElle Peterson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Molecular Analysis ◽  
Rare Case ◽  
Ovarian Teratoma ◽  
Molecular Profile ◽  
Therapeutic Treatment ◽  
Ependymal Tumor ◽  
Experimental Therapies

Primary ovarian ependymoma is a rare neuroectodermal neoplasm that can arise from immature ovarian teratoma. Due to the paucity of this entity, a complete molecular analysis of these tumors has not been done, thus creating a challenge for finding an effective and safe therapeutic treatment. In limited literature, patient with primary ovarian ependymoma showed various responses to an array of individualized therapies ranging from surgeries and chemotherapies. Here, we present a 38-year-old female with persistent ovarian ependymoma with molecular profile similar to traditional central nervous system ependymoma that is irresponsive to multiple cytoreduction and clinical experimental therapies. Therefore, a prompt recognition and reporting of this entity can greatly aid in expanding the understanding and standardization of therapies for this neoplasm.

Preliminary analysis of a U.S. phase II study of the safety and tolerability of proxalutamide (GT0918) in subjects with mCRPC who had progressed on either abiraterone (Abi) or enzalutamide (Enza).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 99-99
Author(s):  
Nicholas J. Vogelzang ◽  
Richard Levin ◽  
Arash Rezazadeh ◽  
Chandler H. Park ◽  
Britt Haley Bolemon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Lipid Lowering ◽  
Early Discontinuation ◽  
Once Daily ◽  
Experimental Therapies ◽  
Daily Dose ◽  
Grade 3 ◽  
Good Treatment Option ◽  
Recommended Phase Ii Dose ◽  
Clinical Trial Information

99 Background: GT0918, an androgen receptor (AR) antagonist, is a new chemical entity with reduced drug accumulation in the CNS. In a phase I dose escalation trial (NCT02826772), GT0918 was well tolerated with some durable responses in mCRPC patients (pts) who had progressed on ≥2 lines of standard and experimental therapies. This Phase 2 was designed to study the safety and efficacy of GT0918 400 mg vs. 500 mg oral daily in mCRPC pts who had progressed on either Abi or Enza with or without prior docetaxel. Methods: Pts with histologically confirmed mCRPC who had progressed on either Abi or Enza with or without prior docetaxel were eligible and randomized to 400 mg or 500 mg of GT0918 administered once daily orally. Pts continued treatment with GT0918 at their assigned dose until disease progression, intolerable toxicities or withdrawal of consent. PSA and labs were checked monthly. Imaging scans (CT/MRI and bone scan), circulating tumor cells and cf-DNA/RNA were performed every 3 months. Results: 61 pts were enrolled at 9 US sites and randomized 1:1 to 400 mg (n = 31) or 500 mg (n = 30) daily dose. All pts had progressed on either Abi (n = 34) or Enza (n = 27). Most of the reported AEs related to GT0918 were grade 1 or 2 as per CTCAE v4.03, but 22 AEs (5.3%) were reported as grade ≥ 3, such as fatigue, increase ALT/AST, rhabdomyolysis, or muscle weakness. Some AEs were due to drug-drug interaction with lipid-lowering medications leading to early discontinuation (26.2%). As of 5 October 2020, twelve pts finished 6 cycles. Among them, three finished 12 cycles and remained on the treatment. Treatment duration showed more pts in the 400 mg cohort with stable disease (SD) on imaging (9/31 finished 6 cycles) compared to the 500 mg cohort (3/30 finished 6 cycles). Further, all three pts who finished 12 cycles had progressed on Abi indicating that GT0918 might be a good treatment option for pts who had progressed on Abi. Conclusions: Proxalutamide (GT0918) administrated orally once a day is well tolerated and resulted in SD in pts who had progressed on either Abi or Enza. The 400 mg/day will be considered as the recommended phase II dose for further clinical trials. GT0918 is warranted for pts failed either Abi or Enza. Clinical trial information: NCT03899467.

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