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Pharmacokinetics of ecteinascidin 743 administered as a 24-h continuous intravenous infusion to adult patients with soft tissue sarcomas: associations with clinical characteristics, pathophysiological variables and toxicity
- Source :
- Cancer Chemotherapy and Pharmacology. 50:309-319
- Publication Year :
- 2002
- Publisher :
- Springer Science and Business Media LLC, 2002.
-
Abstract
- PURPOSE: Ecteinascidin 743 (ET-743) is a potent cytotoxic alkaloid of marine origin that has shown promising evidence of antitumor activity during phase I clinical trials. In the study reported here, the influence of clinical characteristics and pretreatment pathophysiological variables on the pharmacokinetics of ET-743 and their associations with drug-related toxicity was examined in sarcoma patients treated in three phase II clinical trials. METHODS: Adult patients with various histological subtypes of soft tissue sarcoma received 1.5 mg/m(2) of ET-743 by 24-h continuous i.v. infusion once every 3 weeks. Eligibility criteria were similar for each study, except for the histological subtype of the tumor or the extent of prior treatment with other anticancer agents, and all patients had normal or near-normal liver and renal function. The maximum plasma concentration (C(max)) and area under the plasma profile from time zero to infinity (AUC) of the drug were determined during the first cycle of therapy. Patients were evaluated for toxicity every week. RESULTS: Geometric mean +/- SD values of the pharmacokinetic parameters in 69 patients were: C(max) 1.14 +/- 0.52 ng/ml, AUC 39.9 +/- 16.6 ng.h/ml, and total body clearance (CL) 36.7 +/- 16.4 l/h per m(2). The only significant correlation involving physical characteristics of the patients or pretreatment pathophysiological variables was a very weak relationship between alkaline phosphatase and AUC (r=0.39, P
- Subjects :
- Adult
Male
Cancer Research
medicine.medical_specialty
Neutropenia
medicine.drug_class
Renal function
Antineoplastic Agents
Dioxoles
Pharmacology
Toxicology
Gastroenterology
Dexamethasone
Therapeutic index
Liver Function Tests
Pharmacokinetics
Tetrahydroisoquinolines
Internal medicine
medicine
Humans
Antiemetic
Pharmacology (medical)
Infusions, Intravenous
Transaminases
Body surface area
medicine.diagnostic_test
business.industry
Liver Neoplasms
Sarcoma
Middle Aged
Isoquinolines
Oncology
Toxicity
Liver function tests
business
Trabectedin
medicine.drug
Subjects
Details
- ISSN :
- 14320843 and 03445704
- Volume :
- 50
- Database :
- OpenAIRE
- Journal :
- Cancer Chemotherapy and Pharmacology
- Accession number :
- edsair.doi.dedup.....ce91e55761b936424f568d7067c8a79b