Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: a National Cancer Institute Organ Dysfunction Working Group study.
Clin Cancer Res
; 13(12): 3660-6, 2007 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-17575231
ABSTRACT
PURPOSE:
To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patients with hepatic impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. EXPERIMENTALDESIGN:
Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to 130 mg/m(2) every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepatic dysfunction control group A [bilirubin, AST, and AP < or = upper limit of normal (ULN)], mild dysfunction group B (bilirubin < or = ULN, ULN < AST < or = 2.5 x ULN, or ULN < AP < or = 5 x ULN), moderate dysfunction group C (ULN < bilirubin < or = 3.0 mg/dL, AST > 2.5 x ULN, or AP > 5 x ULN), severe dysfunction group D (bilirubin > 3.0 mg/dL, any AST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations.RESULTS:
Dose escalation of single-agent oxaliplatin to 130 mg/m(2) was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patients with a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months.CONCLUSIONS:
Oxaliplatin at 130 mg/m(2) every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction.
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Bases de datos:
MEDLINE
Asunto principal:
Compuestos Organoplatinos
/
Hepatopatías
/
Neoplasias
/
Antineoplásicos
Tipo de estudio:
Clinical_trials
/
Guideline
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos