Paclitaxel Amifostine

In several studies, intravenous amifostine (910 mg/m ) preserved glomerular filtration rate when it was co-administered with cisplatin-containing regimens (213). Even after two cycles containing intravenous cisplatin 50 mg/m plus intravenous ifosfamide and etoposide or paclitaxel, glomerular filtration rate can fall by more than 30%, but concomitant use of amifostine prevented this. Even lower dosages of intravenous amifostine (for example 740 mg/m ) may be effective (220,221). 

Amifostine had no effect on docetaxel and paclitaxel pharmacokinetics, except in one study which found that amifostine extended paclitaxel plasma circulation time. Amifostine appears not to reduce the toxicity of these taxanes. 

In a randomised study, amifostine did not alter the response to, or the phar-maeokineties of, paclitaxel, neither did it protect against paclitaxel-relat-ed neurotoxicity or myelotoxicity. Another study in 8 patients has confirmed that amifostine (750 mg/m as a 15-minute infusion 30 minutes beforehand) had no effect on the pharmacokinetics of paclitaxel 135 to 200 mg/m. Six of the patients were also taking epirubicin and cisplatin. Although the preliminary findings of an earlier study had suggested that pre-treatment with amifostine reduced the AUC of paclitaxel by 29%, the full report of this study concluded that amifostine had no clinically relevant effect on paclitaxel pharmacokinetics. In a study in which patients were given amifostine 500 mg as an infusion over 15 minutes just before low-dose paclitaxel 80 mg/m7 as a one-hour infusion, amifostine reduced maximum plasma levels by about 20%. However, the AUC of paclitaxel was not affected, but the paclitaxel plasma circulation time was prolonged. ... 

The finding in two of these studies - that the toxicity of taxanes was not reduced by amifostine does not support earlier in vitro data where amifostine protected normal tissue from paclitaxel toxicity. ... 

GelmonK, EisenhauerE, Bryce C, Tolcher A, Mayer L, Tomlinson E, Zee B, BlacksteinM, Tomiak E, Yau J, Batist G, Fisher B, Iglesias J. Randomized phase H study of high-dose paclitaxel with or wiAout amifostine in patients with metastatic breast cancer. J Clin Oncol (1999) 17, 3038 7. 

SchuUer J, Czejka L4 Pietrzak C, Springer B, Wirtii M, Schemtiianer G. Influence of the 03 0-protective agent amifostine (AME) on pharmacokinetics (PK) of paclitaxel (PAQ and Taxo-tere (TXT). ProcAm Soc Clin Oncol (1997) 16, 224a. 

Czejka M, Schueller J, Eder I, Reznicek G, Kraule C, Zeleni U, Freitag R. Clinical pharmacokinetics and metabolism of paclitaxel after polychemotiierapy witii tiie c3ftoprotective agent amifostine. Anticancer Res (2000) 20,3871-7. 

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