Antineoplastic activity of products derived from cellulose-containing materials: levoglucosenone and structurally-related derivatives as new alternatives for breast cancer treatment
Summary
Breast cancer is the leading cause of cancer death among women worldwide. For this reason, the development of new therapies is still essential. In this work we have analyzed the antitumor potential of levoglucosenone, a chiral building block derived from the pyrolysis of cellulose-containing materials such as soybean hulls, and three structurally related analogues. Employing human and murine mammary cancer models, we have evaluated the effect of our compounds on cell viability through MTS assay, apoptosis induction by acridine orange/ethidium bromide staining and/or flow cytometry and the loss of mitochondrial p...
Source: Investigational New Drugs - September 3, 2021 Category: Drugs & Pharmacology Source Type: research
A phase i study of ixazomib and erlotinib in patients with advanced solid tumors
Conclusions. The combination of erlotinib and ixazomib was safe and well tolerated among patients with advanced cancer, with preliminary signals of antitumor activity in patients with advanced sarcoma. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 1, 2021 Category: Drugs & Pharmacology Source Type: research
Improved pharmacokinetic and pharmacodynamic profile of a novel PEGylated native Erwinia chrysanthemi L-Asparaginase
Conclusion. Overall, this next generation product PEG-nErA (with improved PK and PD characteristics compared to nErA) would bring a significant advantage to the therapeutic needs of ALL patients and should be further explored in clinical trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 1, 2021 Category: Drugs & Pharmacology Source Type: research
A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma
Conclusions Ponatinib as a single agent inFGFR altered BTC is tolerable with limited clinical activity. This is the first report of prospective assessment ofFGFR inhibition in BTC using ponatinib, and the first study to report its effect on HRQoL. Further development of ponatinib will involve correlative studies to better refine patient selection, focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy, and studies to better understand mechanisms of treatment resistance. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 31, 2021 Category: Drugs & Pharmacology Source Type: research
Design, synthesis and biological evaluation of dual HDAC and VEGFR inhibitors as multitargeted anticancer agents
SummaryHerein, a novel series of dual histone deacetylase (HDAC) and vascular endothelial growth factor receptor (VEGFR) inhibitors were designed, synthesized and biologically evaluated based on previously reported pazopanib-based HDAC and VEGFR dual inhibitors. Most target compounds showed significant HDAC1, HDAC6 and VEGFR2 inhibition, which contributed to their potent antiproliferative activities against multiple cancer cell lines and significant antiangiogenic potencies in both human umbilical vein endothelial cell (HUVEC) tube formation assays and rat thoracic aorta ring assays. Further HDAC selectivity evaluations in...
Source: Investigational New Drugs - August 31, 2021 Category: Drugs & Pharmacology Source Type: research
Successful treatment of a case of hormone receptor –positive metastatic extramammary Paget disease with tamoxifen
SummaryExtramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma that usually is of epidermal origin and shows glandular differentiation and that is treated by wide local excision depending on the disease extent. For widely metastatic disease, however, a standard treatment remains to be established. Similar to breast cancer, EMPD has been found to overexpress human epidermal growth factor receptor 2 (HER2) or hormone receptors (HRs). Whereas HER2-directed therapy was recently shown to be effective for HER2-positive EMPD, the potential role of endocrine therapy for HR-positive EMPD has remained unknown. We here r...
Source: Investigational New Drugs - August 31, 2021 Category: Drugs & Pharmacology Source Type: research
A phase I trial of lurbinectedin in combination with cisplatin in patients with advanced solid tumors
Conclusion The combination of lurbinectedin with cisplatin was not possible in meaningful therapeutic dosage due to toxicity. The addition of aprepitant in combination with cisplatin did not allow increasing the dose due to hematological toxicity, whereas omitting aprepitant increased the incidence of nausea and vomiting. Modest clinical activity was observed in general.Clinical trial registrationwww.ClinicalTrials.gov code: NCT01980667. Date of registration: 11 November 2013. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 28, 2021 Category: Drugs & Pharmacology Source Type: research
Drug-induced colitis on BRAF and MEK inhibitors for BRAF V600E-mutated non-small cell lung cancer: a case report
Conclusion. Severe gastrointestinal toxicities are uncommon with BRAF and MEK inhibitors, although cases of colitis and intestinal perforation have already been reported in literature. The pathogenesis seems to be related to the MAPK pathway inhibition performed by MEK inhibitors. These adverse events should be accounted given the potential to evolve into life-threatening conditions. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 26, 2021 Category: Drugs & Pharmacology Source Type: research
In vitro and clinical investigations to determine the drug-drug interaction potential of entrectinib, a small molecule inhibitor of neurotrophic tyrosine receptor kinase (NTRK)
Conclusions Entrectinib is a CYP3A4 substrate and is sensitive to the effects of coadministered moderate/strong CYP3A4 inhibitors and strong inducers, and requires dose adjustment. Entrectinib is a weak inhibitor of CYP3A4 and P-glycoprotein and no dose adjustments are required with CYP3A4/P- glycoprotein substrates.Registration Number (Study 2) NCT03330990 (first posted online November 6, 2017) As studies 1 and 3 are phase 1 trials in healthy subjects, they are not required to be registered. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 21, 2021 Category: Drugs & Pharmacology Source Type: research
Reforms of regulatory pathways for approval of new antineoplastic drugs in Japan from 2004 to 2019 and accompanying changes in pivotal clinical trial designs
Conclusion The number of indications in oncology approved by the PMDA has been increasing over the past 16 years, alongside changes in regulatory pathways. The 2006 guideline on clinical evaluation had a particular impact on pivotal clinical trial designs. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 21, 2021 Category: Drugs & Pharmacology Source Type: research
A multicenter phase 1/2 study investigating the safety, pharmacokinetics, pharmacodynamics and efficacy of a small molecule antimetabolite, RX-3117, plus nab-paclitaxel in pancreatic adenocarcinoma
Conclusion RX-3117 plus nab-Pac in newly diagnosed met-PC patients demonstrated tolerability, safety, and early treatment efficacy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 21, 2021 Category: Drugs & Pharmacology Source Type: research
Real-world evaluation of second line chemotherapy for patients with advanced non-small cell lung cancer harboring preexisting interstitial lung disease
SummaryBackground. The optimal second and subsequent lines of chemotherapy for patients with non-small cell lung cancer (NSCLC) who have preexisting interstitial lung disease (ILD) are unclear. Hence, we examined the clinical efficacy and safety of second-line chemotherapy in such patients, including any exacerbation of preexisting ILD.Methods. The medical records of patients with NSCLC and preexisting ILD who received both first- and second-line chemotherapy were retrospectively reviewed.Results. Twenty-four patients with a median age of 71 years who were treated between April 2013 and March 2021 were included. The resp...
Source: Investigational New Drugs - August 20, 2021 Category: Drugs & Pharmacology Source Type: research
Anaphylactic shock in a small cell lung cancer patient receiving atezolizumab therapy: a rare but potentially fatal complication
SummaryImmunotherapy has been a revolutionary innovation in cancer therapy in recent years, but it is accompanied by various unique immune-related adverse events (irAEs). Among these irAEs, anaphylactic shock is very rare. Here, we report a case of a patient who developed anaphylactic shock after receiving one dose of atezolizumab. A 74-year-old male patient with small cell lung cancer experienced recurrence 10 years after surgery. After one cycle of treatment, the patient developed a grade 2 rash and recovered after receiving oral methylprednisolone tablets. In the second cycle, atezolizumab was discontinued. Then, the ...
Source: Investigational New Drugs - August 16, 2021 Category: Drugs & Pharmacology Source Type: research
IL-15-induced lymphocytes as adjuvant cellular immunotherapy for gastric cancer
Conclusion Adoptive transfer of ACTIL −15 cells in a mouse model of GC and in patients with advanced GC treated with S1 + oxaliplatin improved survival rates in both, with an acceptable safety profile. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 13, 2021 Category: Drugs & Pharmacology Source Type: research
In vitro selection of DNA aptamers against human osteosarcoma
Conclusions. These results suggest that OS-7.9 could recognize a common protein expressed in these cancer cells, possibly becoming a potential molecular probe for early diagnosis and targeted therapies for metastatic disease. Moreover, to the best of our knowledge, this was the first attempt to generate a DNA aptamer (OS-7.9 aptamer) against the MG-63-cell line by cell-SELEX. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 12, 2021 Category: Drugs & Pharmacology Source Type: research
