Phase 1 and pharmacokinetic study of weekly docosahexaenoic acid-paclitaxel, Taxoprexin, in resistant solid tumor malignancies
| Autor: | ChauHwei J. Fu, Paula M. Fracasso, Benjamin R. Tan, Ramaswamy Govindan, Jonathan Wildi, Robert E. Bellet, Allison N. Creekmore, Joel Picus, Merrill J. Egorin, Stephen C. Zumbrun, Feng Gao, Sherry A. Goodner, Matthew J. Ellis, Helen S. Pentikis, Gerald P. Linette |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Adolescent Docosahexaenoic Acids Maximum Tolerated Dose Paclitaxel Pharmacology Neutropenia Toxicology Gastroenterology Sensitivity and Specificity chemistry.chemical_compound Pharmacokinetics Tandem Mass Spectrometry Internal medicine Neoplasms Antineoplastic Combined Chemotherapy Protocols medicine Neoplasm Humans Pharmacology (medical) Aged Taxane business.industry Melanoma DHA-paclitaxel Middle Aged medicine.disease Oncology chemistry Drug Resistance Neoplasm Toxicity Female business Chromatography Liquid |
| Zdroj: | Cancer chemotherapy and pharmacology. 63(3) |
| ISSN: | 1432-0843 |
| Popis: | To determine the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics of weekly docosahexaenoic acid-paclitaxel (DHA-paclitaxel), a taxane fatty acid conjugate. Docosahexaenoic acid-paclitaxel was administered by 2-hour i.v. infusion weekly for three out of four weeks. DHA-paclitaxel 200 mg/m2 was dose escalated by 100 mg/m2 per cohort to 600 mg/m2. Blood samples for pharmacokinetics of DHA-paclitaxel and paclitaxel derived from DHA-paclitaxel were collected. Twenty-one patients received 42 cycles of treatment over five dose levels. Grade 3/4 neutropenia occurred in five patients but was not dose limiting. Grade 3 hyperbilirubinemia, a DLT, and grade 1 sensory neuropathy occurred at the highest dose level. PK analyses demonstrated dose proportional C max and AUC0−24. Limited accumulation of DHA-paclitaxel or paclitaxel occurred with weekly treatment. Increased DHA-paclitaxel and paclitaxel AUC0−24 were associated with increased neutropenia. Of the 19 patients evaluable for response, three patients with esophageal, melanoma and colon carcinoma had stable disease for 11, 16, and 17 weeks, respectively. Docosahexaenoic acid-paclitaxel administered weekly to a maximum dose of 600 mg/m2 was well-tolerated. The slow release of paclitaxel from DHA-paclitaxel and the weekly schedule approximates continuous infusion paclitaxel which may be more active than every 3 week or weekly taxanes. |
| Databáze: | OpenAIRE |
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