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| Differential modulation of cisplatin accumulation in leukocytes and tumor cell lines by the paclitaxel vehicle Cremophor EL |
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| Author(s): de Vos AI, Nooter K, Verweij J, Loos WL, Brouwer E, de Bruijn P, Ruijgrok EJ, van der Burg MEL, Stoter G, Sparreboom A |
| Source: ANNALS OF ONCOLOGY Volume: 8 Issue: 11 Pages: 1145-1150 Published: NOV 1997 |
| Times Cited: 14 References: 33 |
| Abstract: Background. Several clinical studies have shown that polychemotherapy with the taxanes paclitaxel or docetaxel preceded or followed by cisplatin is associated with important schedule-dependent differences in toxicities, such as leukocytopenia. In general, the pharmacokinetics of both drugs during the combined treatment are unaltered, suggesting that a pharmacodynamic interaction might have occurred. Materials and methods: In order to gain insight into this pharmacologic interaction, we performed in vitro drug accumulation studies using peripheral blood leukocytes and a panel of tumor and non-malignant cell lines with paclitaxel and docetaxel, as wel as with their respective formulation vehicles Cremophor EL and Tween 80.
Results: Our results show a significant reduction in the intracellular cisplatin concentration in leukocytes of up to 42% in the presence of Cremophor EL and Tween 80 as compared to the control. This pharmacodynamic interaction of these surfactants with cisplatin seems to be specific for haematopoietic cells, and does not occur in solid tumor cells.
Conclusion: The present data suggest that the pharmaceutical vehicles Cremophor EL and Tween 80 might contribute to the reduced cisplatin-associated myelotoxicity observed in the clinical combination chemotherapy studies with paclitaxel and docetaxel.
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| Document Type: Article |
| Language: English |
| Reprint Address: Sparreboom, A (reprint author), Rotterdam Canc Inst, Daniel Den Hoed Klin, Dept Med Oncol, Lab Expt Chemotherapy Pharmacol & Tumor Biol, POB 5201, NL-3008 AE Rotterdam, Netherlands |
Addresses:
1. Rotterdam Canc Inst, Daniel Den Hoed Klin, Dept Med Oncol, Lab Expt Chemotherapy Pharmacol & Tumor Biol, NL-3008 AE Rotterdam, Netherlands
2. Univ Rotterdam Hosp, NL-3008 AE Rotterdam, Netherlands
3. Erasmus Univ, Dept Clin Microbiol, Rotterdam, Netherlands |
| Publisher: KLUWER ACADEMIC PUBL, SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS |
| Subject Category: Oncology |
| IDS Number: YL777 |
| ISSN: 0923-7534 |
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