EGFR-TKI re-administration after osimertinib failure in T790M mutation loss cases with re-biopsy
SummaryData on the re-administration of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) after osimertinib failure in patients with T790M-positive non –small cell lung cancer (NSCLC) is limited. EGFR-TKI re-administration efficacy may vary between patients with T790M loss and those with T790M persistent with re-biopsy after osimertinib treatment. Patients who received EGFR-TKI re-administration (gefitinib, erlotinib, afatinib, dacomitinib, and o simertinib) after osimertinib failure were identified from our database. T790M mutation status before EGFR-TKI re-administration was analyzed via repeat ...
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Phase I study to evaluate of the gastric pH-dependent drug interaction between famitinib and the proton pump inhibitor omeprazole in healthy subjects
SummaryTo evaluate the potential gastric pH-dependent drug-drug interaction (DDI), safety and tolerability of famitinib co-administered with omeprazole in healthy subjects. Twenty healthy subjects were enrolled in a single-center, single-arm, open-label, fixed-sequence study. Famitinib was administered as a single oral 25 mg under a fasting condition on day 1, omeprazole (40 mg once daily) was given on days 10–14, concomitantly with famitinib on day 15, and for the follow-up 7 additional days (days 16–22). Blood samples were collected for the pharmacokinetic analysis of famitinib and its metabolite SHR116637 f ollow...
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab
SummaryAlpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment. In this prospective multicenter study, we aimed to investigate an optimal threshold of AFP response in Atez/Bev treatment. Out of 284 patients with unresectable HCC who were treated with Atez/Bev, 91 patients with AFP ≥ 10 ng/ml were enrolled in the mult...
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Comparison of dual mTORC1/2 inhibitor AZD8055 and mTORC1 inhibitor rapamycin on the metabolism of breast cancer cells using proton nuclear magnetic resonance spectroscopy metabolomics
AbstractDual mTORC1/2 inhibitors may be more effective than mTORC1 inhibitor rapamycin. Nevertheless, their metabolic effects on breast cancer cells have not been reported. We compared the anti-proliferative capacity of rapamycin and a novel mTORC1/2 dual inhibitor (AZD8055) in two breast cancer cell lines (MDA-MB-231 and MDA-MB-453) and analyzed their metabolic effects using proton nuclear magnetic resonance (1H NMR) spectroscopy-based metabolomics. We found that AZD8055 more strongly inhibited breast cancer cell proliferation than rapamycin. The half-inhibitory concentration of AZD8055 in breast cancer cells was almost...
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Carbidopa suppresses estrogen receptor-positive breast cancer via AhR-mediated proteasomal degradation of ER α
SummaryEstrogen receptor- α (ERα) promotes breast cancer, and ER-positive cancer accounts for ~ 80% of breast cancers. This subtype responds positively to hormone/endocrine therapies involving either inhibition of estrogen synthesis or blockade of estrogen action. Carbidopa, a drug used to potentiate the therapeutic ef ficacy of L-DOPA in Parkinson's disease, is an agonist for aryl hydrocarbon receptor (AhR). Pharmacotherapy in Parkinson’s disease decreases the risk for cancers, including breast cancer. The effects of carbidopa on ER-positive breast cancer were evaluated in cell culture and in mouse xenografts. The...
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Long-term response in a patient with adenocarcinoma harboring both common and uncommon EGFR mutations
AbstractRecently, we read a paper “Dacomitinib overcomes afatinib-refractory carcinomatous meningitis in a lung cancer patient harbouring EGFR Ex.19 deletion and G724S mutation” published in Investigational New Drugs. Their patient had a very rare compound EGFR mutation. To share our experience, we present a case of 58-year-old man with a long-term response to afatinib in a patient with previously unreported compound EGFR mutation. In patients with rare compound EGFR mutations, afatinib might be one of the treatment option. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Correction to: Analysis of melanoma tumor antigens and immune subtypes for the development of mRNA vaccine
(Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Icotinib, an EGFR tyrosine kinase inhibitor, as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma: a multicenter, open-label, single-arm, phase II study (ICAPE)
This study (ICAPE) evaluated the efficacy of icotinib as adjuvant therapy for patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma. Patients with stage IIA-IIIA EGFR-mutant non-small-cell lung adenocarcinoma were enrolled in the multicenter, open-label, single-arm, phase II study. Eligible patients received oral icotinib 125 mg thrice daily for 1.5 years after complete surgical resection. The primary endpoint was disease-free survival (DFS). Between March 2014 and January 2018, 79 patients were enrolled. The median follow-up time was 39.7 months with a median DFS and overall survival (OS) of 41.4 m...
Source: Investigational New Drugs - November 10, 2022 Category: Drugs & Pharmacology Source Type: research
Predictive performance of PD-L1 tumor proportion score for nivolumab response evaluated using archived specimens in patients with non-small cell lung cancer experiencing a postoperative recurrence
ConclusionThe study revealed that archived surgical specimens are inadequate for assessing the predictive ability of PD-L1 for nivolumab response, while rebiopsy specimens are adequate. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 5, 2022 Category: Drugs & Pharmacology Source Type: research
The influence of verapamil on the pharmacokinetics of the pan-HER tyrosine kinase inhibitor neratinib in rats: the role of P-glycoprotein-mediated efflux
SummaryNeratinib, an irreversible pan-HER tyrosine kinase inhibitor, has been approved for the treatment of HER2-positive (HER2+) early-stage and brain metastatic breast cancer. Thus far, the pharmacology effects and pharmacodynamics of neratinib have been well studied. However, the disposition of neratinib and its influencing factors in vivo remain unclear. P-glycoprotein (P-gp), one of the most extensively studied transporters, substantially restricts penetration of drugs into the body or deeper compartments (i.e., blood-brain barrier, BBB), regarding drug resistance and drug-drug interactions. Thereby, the aim of this s...
Source: Investigational New Drugs - November 4, 2022 Category: Drugs & Pharmacology Source Type: research
Oral formulation of bendamustine hydrochloride for patients with advanced solid tumors; a phase 1 study
SummaryTo determine the maximum tolerated dose (MTD) and recommended dose (RD) of orally-administered bendamustine in Japanese patients with advanced solid tumors. The optimal dosing schedule, safety, pharmacokinetics, and preliminary antitumor effects were also evaluated. A multicenter, open-label trial with a standard 3 + 3 design and dose escalation by dose-limiting toxicity (DLT) was conducted. The treatment schedules were once daily for 7, 14, and 21 days every 3 weeks as one cycle. The total dose per cycle was increased from 175 to 840 mg/m2. Eighteen patients were enrolled in this study. DLT occurred in one ...
Source: Investigational New Drugs - November 4, 2022 Category: Drugs & Pharmacology Source Type: research
Phase 1 study of the safety, pharmacokinetics, and preliminary efficacy of CA102N as monotherapy and in combination with trifluridine-tipiracil in patients with locally advanced or metastatic solid tumors
SummaryCA102N is a covalently bound conjugate of modified nimesulide (Nim) and NaHA, the sodium salt of hyaluronic acid (HA). HA is a natural ligand of cluster of differentiation 44 (CD44), which is over-expressed in colorectal cancer (CRC). CA102N is designed to deliver nimesulide directly to the tumor via the interaction of HA and CD44. A Phase 1, 2-part (dose escalation, dose expansion), non-randomized, open-label, first-in-human study of CA102N, as monotherapy and in combination with trifluridine-tipiracil, was conducted in patients with locally advanced or metastatic solid tumors. The CA102N doses evaluated were 0.36 ...
Source: Investigational New Drugs - November 4, 2022 Category: Drugs & Pharmacology Source Type: research
Necitumumab plus gemcitabine and cisplatin in previously treated lung squamous cell carcinoma
Conclusion: N + GC displayed good efficacy in the second line or later treatment among patients with LSCC. This study suggested that N + GC is a useful option even after second-line treatment of advanced-stage or recurrent LSCC, although the management of adverse events is essential. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 4, 2022 Category: Drugs & Pharmacology Source Type: research
TRIM59 guards ER proteostasis and prevents Bortezomib-mediated colorectal cancer (CRC) cells ’ killing
AbstractThe endoplasmic reticulum (ER) is a critical organelle that preserves the protein homeostasis of cells. Under various stress conditions, cells evolve a degree of capacity to maintain ER proteostasis, which is usually augmented in tumor cells, including colorectal cancer (CRC) cells, to bolster their survival and resistance to apoptosis. Bortezomib (BTZ) is a promising drug used in CRC treatment; however, its main limitation result from drug resistance. Here, we identified the role of tripartite motif-containing protein 59 (TRIM59) –a protein localized on the ER membrane– in the prevention of BTZ-mediated CRC ki...
Source: Investigational New Drugs - October 28, 2022 Category: Drugs & Pharmacology Source Type: research
Tetra-arsenic tetra-sulfide enhances NK-92MI mediated cellular immunotherapy in all-trans retinoic acid-resistant acute promyelocytic leukemia
In conclusion, our findings confirmed the potential of As4S4 as an adjuvant for NK-92MI in the treatment of ATRA-resistant APL. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 26, 2022 Category: Drugs & Pharmacology Source Type: research
