Abstract | PURPOSE: PATIENTS AND METHODS: A total of six patients received oral paclitaxel as single agent given as a single dose of 100 mg on day 1, oral paclitaxel 100 mg in combination with cyclosporin A (CsA) 10 mg/kg both given as a single dose on day 8, and i.v. paclitaxel ( Taxol) 100 mg as a 3-h infusion on day 15. RESULTS: The AUC (mean +/- standard deviation) values of paclitaxel after oral administration without CsA and with CsA were 476 +/- 254 and 967 +/- 779 ng/ml h, respectively. T (max) was 4.0 +/- 0.9 h after oral paclitaxel without CsA, and 6.0 +/- 3.1 h after oral paclitaxel with CsA. The mean AUC after oral administration as single agent was 13% of the AUC after i.v. administration of paclitaxel, and increased to 26% after co-administration with CsA. No haematological toxicities were observed, and only mild (CTC-grade 1 and 2) non-hematological toxicities occurred after oral intake of paclitaxel with or without CsA. CONCLUSION: The AUC of the new polymeric paclitaxel formulation increased a factor 2 in combination with CsA, which confirms that CsA co-administration can also improve exposure to paclitaxel after oral administration of a polymeric formulation. Because of the delayed release of paclitaxel from this formulation, we hypothesize that a split-dose regimen of CsA where it is administered before and after paclitaxel administration will further increase the systemic exposure to paclitaxel up to therapeutic levels. The formulation was well tolerated at the dose of 100 mg without induction of severe toxicities.
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Authors | S A Veltkamp, C Alderden-Los, A Sharma, H Rosing, J H Beijnen, J H M Schellens |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 59
Issue 1
Pg. 43-50
(Jan 2007)
ISSN: 0344-5704 [Print] Germany |
PMID | 16680462
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Capsules
- Immunosuppressive Agents
- Polymers
- Cyclosporine
- Paclitaxel
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Topics |
- Administration, Oral
- Adult
- Antineoplastic Agents, Phytogenic
(administration & dosage, adverse effects, pharmacokinetics)
- Area Under Curve
- Capsules
- Central Nervous System Diseases
(chemically induced, epidemiology)
- Chemistry, Pharmaceutical
- Cyclosporine
(therapeutic use)
- Female
- Gastrointestinal Diseases
(chemically induced, epidemiology)
- Half-Life
- Hematologic Diseases
(chemically induced, epidemiology)
- Humans
- Immunosuppressive Agents
(therapeutic use)
- Injections, Intravenous
- Male
- Middle Aged
- Neoplasms
(complications, drug therapy)
- Paclitaxel
(administration & dosage, adverse effects, pharmacokinetics)
- Polymers
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