A randomized cross-over trial to determine the effect of Cremophor EL on the pharmacodynamics and pharmacokinetics of carboplatin chemotherapy
| Autor: | Michael Michael, Lorraine K. Webster, Michael J. Millward, Andrew G. Ellis, Kerrie Stokes, Kally Yuen, Danny Rischin, Sherene Loi |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Glycerol Male Cancer Research endocrine system diseases Metabolic Clearance Rate medicine.medical_treatment Antineoplastic Agents Pharmacology Toxicology Carboplatin Surface-Active Agents chemistry.chemical_compound Pharmacokinetics Neoplasms Humans Medicine Pharmacology (medical) neoplasms Aged Aged 80 and over Cisplatin Chemotherapy Cross-Over Studies business.industry Middle Aged Crossover study female genital diseases and pregnancy complications Gemcitabine Oncology chemistry Paclitaxel Area Under Curve Pharmacodynamics Female business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 54:407-414 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | Paclitaxel, when combined with carboplatin, exhibits a platelet-sparing effect. Paclitaxel is formulated in Cremophor EL (CrEL), which has been shown in preclinical models to reduce haematological toxicity from radiotherapy and chemotherapy. We sought to determine the effect of a 3-h infusion of 20 ml/m2 (equivalent to 175 mg/m2 paclitaxel) CrEL on myelosuppression following carboplatin chemotherapy, and the effect of CrEL on carboplatin pharmacokinetics.A total of 16 patients with locally advanced or metastatic cancer were randomized to receive either CrEL or saline over 3 h prior to carboplatin (area under the curve, AUC, 5-7). Each patient was subsequently crossed over to the other treatment. Blood samples were collected at selected time-points for estimation of platinum AUC and 24-h platinum levels. Full blood counts were obtained three times per week.Of the 16 patients randomized, 15 were evaluable. Myelosuppression was measured by percentage fall at nadir and nadir levels. No significant differences were obtained when comparing CrEL and saline with respect to the above end-points after adjusting for multiple testing. There was no evidence to indicate that CrEL altered the pharmacokinetics of carboplatin.CrEL at this dose and schedule does not appear to be a major contributory factor to the platelet-sparing effect of paclitaxel when combined with carboplatin, nor does it alter the pharmacokinetics of carboplatin. |
| Databáze: | OpenAIRE |
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