Dose-Response Relationship in Phase I Clinical Trials: A European Drug Development Network (EDDN) Collaboration Study
| العنوان: | Dose-Response Relationship in Phase I Clinical Trials: A European Drug Development Network (EDDN) Collaboration Study |
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| المؤلفون: | Richard H. Wilson, Stan B. Kaye, Andre T. Brunetto, Jean-Charles Soria, Nicolas Penel, Patrick Schöffski, Ruth Plummer, Carlos Gomez-Roca, Josep Tabernero, Silvia Marsoni, Jan H.M. Schellens, Philippe A. Cassier, Jeff Evans, Gianluca Del Conte, Victor Moreno Garcia, Rafael Morales-Barrera, Jaap Verweij, David Olmos, Elisa Gallerani, Emile E. Voest |
| المساهمون: | Medical Oncology |
| المصدر: | Clinical Cancer Research, 20(22), 5663. American Association for Cancer Research Inc. Clinical Cancer Research, 20(22), 5663-5671. American Association for Cancer Research Inc. |
| بيانات النشر: | American Association for Cancer Research Inc., 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Adolescent, Databases, Factual, Antineoplastic Agents, Pharmacology, Young Adult, Neoplasms, Internal medicine, medicine, High doses, Humans, In patient, Objective response, Aged, Aged, 80 and over, Clinical Trials, Phase I as Topic, Dose-Response Relationship, Drug, business.industry, Cancer, Middle Aged, medicine.disease, Surgery, Europe, Clinical trial, Dose–response relationship, Treatment Outcome, Drug development, Conventional chemotherapy, Female, Drug Monitoring, Dose-effect relationship, business |
| الوصف: | Introduction: Because a dose–response relationship is characteristic of conventional chemotherapy, this concept is widely used for the development of novel cytotoxic (CTX) drugs. However, the need to reach the MTD to obtain optimal benefit with molecularly targeted agents (MTA) is controversial. In this study, we evaluated the relationship between dose and efficacy in a large cohort of phase I patients with solid tumors. Experimental Design: We collected data on 1,182 consecutive patients treated in phase I trials in 14 European institutions in 2005–2007. Inclusion criteria were: (i) patients treated within completed single-agent studies in which a maximum-administered dose was defined and (ii) RECIST/survival data available. Results: Seventy-two percent of patients were included in trials with MTA (N = 854) and 28% in trials with CTX (N = 328). The objective response (OR) rate was 3% and disease control at 6 months was 11%. OR for CTX was associated with higher doses (median 92% of MTD); this was not the case for MTA, where patients achieving OR received a median of 50% of MTD. For trials with MTA, patients treated at intermediate doses (40%–80%) had better survival compared with those receiving low or high doses (P = 0.038). On the contrary, there was a direct association between higher dose and better OS for CTX agents (P = 0.003). Conclusion: Although these results support the development of novel CTX based on MTD, we found no direct relationship between higher doses and response with MTA in unselected patients. However, the longest OS was seen in patients treated with MTA at intermediate doses (40%–80% of MTD). Clin Cancer Res; 20(22); 5663–71. ©2014 AACR. |
| وصف الملف: | application/pdf |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0961e78aa61a69bef8e703b29592228aTest https://pure.eur.nl/en/publications/c8b7a3aa-b68c-49f4-974b-beba29c5fd50Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0961e78aa61a69bef8e703b29592228a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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