Dose-finding designs for trials of molecularly targeted agents and immunotherapies
| Autor: | Cody Chiuzan, Jonathan Shtaynberger, Jimmy Duong, Shing M. Lee, Gary K. Schwartz, Gulam Abbas Manji, Anastasia Ivanova |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Statistics and Probability Oncology medicine.medical_specialty Maximum Tolerated Dose Web of science medicine.medical_treatment Antineoplastic Agents Medical Oncology Article Targeted therapy Toxicology 03 medical and health sciences Dose finding 0302 clinical medicine Neoplasms Internal medicine medicine Humans Pharmacology (medical) Molecular Targeted Therapy Pharmacology Clinical Trials Phase I as Topic Dose-Response Relationship Drug business.industry Immunotherapy Radiation therapy 030104 developmental biology 030220 oncology & carcinogenesis Maximum tolerated dose Early phase business |
| DOI: | 10.17615/97xj-4d96 |
| Popis: | Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, the adoption of these designs continues to remain low. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|