Phase I oncology studies: evidence that in the era of targeted therapies patients on lower doses do not fare worse.
Clin Cancer Res
; 16(4): 1289-97, 2010 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-20145187
ABSTRACT
PURPOSE:
To safely assess new drugs, cancer patients in initial cohorts of phase I oncology studies receive low drug doses. Doses are successively increased until the maximum tolerated dose (MTD) is determined. Because traditional chemotherapy is often more effective near the MTD, ethical concerns have been raised about administration of low drug doses to phase I patients. However, a substantial portion of oncology trials now investigate targeted agents, which may have different dose-response relationships than cytotoxic chemotherapies. EXPERIMENTALDESIGN:
Twenty-four consecutive trials treating 683 patients between October 1, 2004, and June 30, 2008, at MD Anderson Cancer Center were analyzed. Patients were assigned to a low-dose (RESULTS:
Even when excluding patients above the MTD, there was an early trend favoring the low- versus high-dose group in time-to-treatment failure, with 32.9% versus 25.2% of patients on therapy at 3 months (P = 0.08). In addition, the low-dose group fared at least as well as the other groups in all other outcomes, including response rate, progression-free survival, overall survival, and toxicity.CONCLUSIONS:
These data may help alleviate concerns that patients who receive low drug doses on contemporary phase I oncology trials fare worse and suggest targeted agents may have different dose-response relationships than cytotoxic chemotherapies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sistemas de Liberación de Medicamentos
/
Ensayos Clínicos Fase I como Asunto
/
Neoplasias
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos