Purpose: Nanoparticles or carrier-mediated agents have been designed to prolong drug circulation time, increase tumor delivery, and improve therapeutic index compared to their small-molecule counterparts. The starting dose for phase I studies of small molecules and nanoparticles anticancer agents is based on the toxicity profile of the most sensitive species (e.g., rat or canine), but the optimal animal model for these studies of nanoparticles is unclear. The objective of this study was to evaluate the design, progression, and outcomes of phase I studies of nanoparticles compared with small-molecule anticancer agents.
Experimental Design: In preclinical studies, the maximum tolerated dose (MTD) in rats and dogs was evaluated for nanoparticles and their respective small molecules. In phase I clinical trials in patients with advanced solid tumors, the basis for starting dose, the number of dose escalations, number of patients enrolled, and the ratio of MTD to starting dose was determined for nanoparticles and small molecules.
Results: The mean ratio of MTD to starting dose in clinical phase I studies was significantly greater for nanoparticles (13.9 ± 10.8) compared with small molecules (2.1 ± 1.1; P = 0.005). The number of dose levels in a clinical phase I study was also significantly greater for nanoparticles (7.3 ± 2.9) compared with small molecules (4.1 ± 1.5; P = 0.008).
Conclusions: The degree of dose escalation from starting dose to MTD was significantly greater for nanoparticles as compared with small-molecule anticancer drugs. These findings necessitate the need to identify the most appropriate preclinical animal model to use when evaluating nanoparticles toxicity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1158/1078-0432.CCR-12-3649 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Luteolin Alleviates Ulcerative Colitis in Mice by Modulating Gut Microbiota and Plasma Metabolism.
Nutrients
January 2025
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Background/objectives: Ulcerative colitis (UC) is a chronic and easily recurrent inflammatory bowel disease. The gut microbiota and plasma metabolites play pivotal roles in the development and progression of UC. Therefore, therapeutic strategies targeting the intestinal flora or plasma metabolites offer promising avenues for the treatment of UC.
View Article and Find Full Text PDFPossibility of Using NO Modulators for Pharmacocorrection of Endothelial Dysfunction After Prenatal Hypoxia.
Pharmaceuticals (Basel)
January 2025
Department of Microbiology, Virology and Immunology, I. Horbachevsky Ternopil State Medical University, 46001 Ternopil, Ukraine.
Prenatal hypoxia (PH) is a key factor in the development of long-term cardiovascular disorders, which are caused by various mechanisms of endothelial dysfunction (ED), including those associated with NO deficiency. This emphasizes the potential of therapeutic agents with NO modulator properties, such as Thiotriazoline, Angiolin, Mildronate, and L-arginine, in the treatment of PH. Pregnant female rats were given a daily intraperitoneal dose of 50 mg/kg of sodium nitrite starting on the 16th day of pregnancy.
View Article and Find Full Text PDFMultivitamin Supplementation and Fertility Outcome: A Retrospective Single-Center Cohort Study and the Clinical and Medicolegal Value of Nutritional Counseling.
Life (Basel)
January 2025
Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy.
Resveratrol can beneficially affect growth and follicle development and lead to improved sperm function parameters in pre-clinical studies, while information from clinical studies is still inconclusive. This study aims to evaluate the biological and clinical impact of a resveratrol-based multivitamin supplement on level II assisted reproduction cycles (IVF and intracytoplasmic sperm injection [ICSI]). A retrospective, case-control study, involving 70 infertile couples undergoing IVF/ICSI cycles, was conducted at the Assisted Reproductive Center, Obstetrics and Gynecology Unit-Villa Sofia-Cervello Hospital in Palermo.
View Article and Find Full Text PDFDetermining ED90 of Flumazenil for Selective Respiratory Distress Improvement Using Remimazolam During Endoscopic Submucosal Dissection of Gastric Neoplasms: A Prospective Study.
Cancers (Basel)
January 2025
Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
Background: Patients undergoing endoscopic submucosal dissection under monitored anesthesia care (MAC) with remimazolam may develop respiratory distress during the procedure. In these cases, low doses of flumazenil improved respiratory distress without completely reversing sedation, which is a novel phenomenon. This study aimed to explore the ED90 of flumazenil to selectively improve respiratory distress in patients with MAC treated with remimazolam.
View Article and Find Full Text PDFPhase II Study of Atezolizumab and Bevacizumab Combination Therapy for Patients with Advanced Hepatocellular Carcinoma Previously Treated with Lenvatinib.
Cancers (Basel)
January 2025
Department of Gastroenterology, Kanazawa University Hospital, Kanazawa 920-8641, Ishikawa, Japan.
: Atezolizumab and bevacizumab combination therapy has been established as a standard of care for first-line treatment; however, its efficacy and safety have not been fully evaluated for patients previously treated with systemic therapy. : In this phase II trial, patients with advanced hepatocellular carcinoma previously treated with lenvatinib were enrolled to receive a dose of 1,200 mg of atezolizumab and 15 mg/kg of bevacizumab every 3 weeks. The primary endpoint was progression-free survival.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!