scholarly journals Drug interaction of antitumor drugs. III. Antitumor activity of tegafur in lipopolysaccharide-treated mice.

1982 ◽  
Vol 32 (6) ◽  
pp. 1135-1142 ◽  
Author(s):  
Ken-ichi SASAKI ◽  
Shinobu FURUSAWA ◽  
Giichi TAKAYANAGI
Keyword(s):  
Drug Interaction ◽  
Antitumor Activity ◽  
Antitumor Drugs

Initial results from a phase 1b study of ORIC-101, a glucocorticoid receptor antagonist, in combination with nab-paclitaxel in patients with advanced solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2553-2553
Author(s):  
Raghad Muhsin Abdul-Karim ◽  
Anthony W. Tolcher ◽  
Shivaani Kummar ◽  
Manish R. Patel ◽  
Alexander I. Spira ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Antitumor Activity ◽  
Glucocorticoid Receptor ◽  
Solid Tumors ◽  
Mononuclear Cells ◽  
Nuclear Hormone Receptor ◽  
Tolerability Profile ◽  
Once Daily ◽  
Multiple Tumor ◽  
Drug Drug Interaction

2553 Background: ORIC-101 is a potent and selective, orally bioavailable, small molecule antagonist of the glucocorticoid receptor (GR). Preclinical studies have demonstrated that activation of GR signaling leads to decreased responsiveness to chemotherapeutics (eg, taxanes) and antiandrogens across multiple tumor types. Mechanistically, ORIC-101 inhibits GR transcriptional activity and blocks the prosurvival signals mediated by the activated nuclear hormone receptor. Methods: A 3+3 dose escalation design was used to assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and select the Recommended Phase 2 Dose (RP2D) of ORIC-101 in combination with nab-paclitaxel (nab-pac; NCT03928314). ORIC-101 doses ranging from 80 to 240 mg once daily, given either intermittently or in a continuous dosing regimen, were evaluated in combination with weekly nab-pac at 75 or 100 mg/m2. Plasma PK and PD biomarkers were assessed on day 1 and after repeat dosing. PD modulation in blood-derived peripheral blood mononuclear cells (PBMCs) was assessed by RT-qPCR for GR target genes. Antitumor activity was assessed by RECIST v1.1. Results: 21 patients with 10 different solid tumors, with and without a prior taxane, were treated in 5 cohorts. ORIC-101 exposure increased with dose, with no evidence for drug-drug interaction with nab-pac. In the initial cohort at 240 mg ORIC-101 and 100 mg/m2 nab-pac, 2 patients experienced dose limiting toxicities (DLTs) of Grade 3 fatigue and Grade 4 neutropenia/thrombocytopenia, respectively. No further DLTs were observed in subsequent cohorts and the RP2D was established as 160 mg ORIC-101 dosed once daily continuously for 21 days with nab-pac 75 mg/m2 given on days 1, 8, and 15 of each 28-day cycle, without requirement for prophylactic granulocyte colony-stimulating factor (G-CSF). The most common (> 15%), all grade treatment-related adverse events (AEs) were nausea (38%), diarrhea (33%), fatigue (29%), leukopenia (29%), neutropenia (29%), anemia (24%), and 19% of patients had increased liver function tests and alopecia. Biomarker data demonstrated ORIC-101-induced reduction in GR target gene expression in PBMCs, indicating PD modulation at all dose levels of ORIC-101. Preliminary antitumor activity was observed in 3 taxane-refractory patients with breast, endometrial, and pancreatic cancers. Conclusions: The combination of ORIC-101 and nab-paclitaxel demonstrated an acceptable tolerability profile and does not require prophylactic G-CSF. PK and PD showed no evidence of drug-drug-interaction and demonstrated GR target inhibition. Preliminary antitumor activity was observed in patients with solid tumors that previously progressed on a taxane-containing regimen. Dose expansion is ongoing at the RP2D in dedicated pancreatic, ovarian, triple negative breast cancers, and tissue-agnostic cohorts. Clinical trial information: NCT03928314.

Evaluation of antitumor activities of hyaluronate binding antitumor drugs: synthesis, characterization and antitumor activity

1996 ◽  
Vol 4 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Kazuo Akima ◽  
Hisashi Ito ◽  
Yuhei Iwata ◽  
Kayoko Matsuo ◽  
Nobutoshi Watari ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Antitumor Drugs ◽  
Antitumor Activities

In Vitro Antitumor Activity of 9-Nitro-Camptothecin as a Single Agent and in Combination with other Antitumor Drugs

2006 ◽  
Vol 922 (1) ◽  
pp. 293-297 ◽  
Author(s):  
RALPH J. BERNACKI ◽  
PAULA PERA ◽  
PETER GAMBACORTA ◽  
YSEULT BRUN ◽  
WILLIAM R. GRECO
Keyword(s):  
Antitumor Activity ◽  
Single Agent ◽  
Antitumor Drugs

scholarly journals Synthesis of chimeric amides of 2-arilaminopyrimidine series

2020 ◽  
Vol 56 (2) ◽  
pp. 166-180
Author(s):  
Zh. V. Ignatovich
Keyword(s):  
Antitumor Activity ◽  
Antitumor Drugs ◽  
Methodological Approaches ◽  
Amino Pyrimidine ◽  
Chimeric Molecules ◽  
Pyrimidine Fragment

Methodological approaches to the synthesis of 2-arylpyrimidine amides with predicted antitumor activity using the design of chimeric molecules by combining pharmacophore fragments of known antitumor drugs are considered. The results of the synthesis of chimeric amides containing, along with the 2-amino-pyrimidine fragment, fragments of other nitrogen and oxygen-containing heterocycles (piperazine, morpholine, isoxazole, etc.), aromatic cycles (benzene, methylnitroaniline, phenylenediamine) and functional (methyl-, amino-, carboxy-, etc.) groups in different positions of the molecule, are presented.

Self-assembly of pH-responsive dextran-g-poly(lactide-co-glycolide)-g-histidine copolymer micelles for intracellular delivery of paclitaxel and its antitumor activity

RSC Advances ◽  
2016 ◽  
Vol 6 (28) ◽  
pp. 23693-23701 ◽  
Author(s):  
Jiulong Zhang ◽  
Kang Chen ◽  
Ying Ding ◽  
Xiu Xin ◽  
Wenpan Li ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Self Assembly ◽  
Intracellular Delivery ◽  
Antitumor Drugs ◽  
Ph Responsive ◽  
Copolymer Micelles

Herein, dextran (DX) was conjugated with poly(lactide-co-glycolide) (PLGA) and histidine (His) to prepare a pH-responsive nanocarrier, dextran-g-poly(lactide-co-glycolide)-g-histidine (HDP) micelles, for the delivery of antitumor drugs.

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