High-dose Cisplatin with amifostine: ototoxicity and pharmacokinetics
| Autor: | Gunnar Wagenius, Johan Hansson, Hans Ehrsson, Göran Laurell, Inger Wallin, Andreas Ekborn, Staffan Eksborg |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Skin Neoplasms Side effect Metabolic Clearance Rate Hearing Loss Sensorineural Antineoplastic Agents Pharmacology Drug Administration Schedule Amifostine Pharmacokinetics Ototoxicity medicine Humans Prospective Studies Melanoma Aged Neoplasm Staging Cisplatin Dose-Response Relationship Drug business.industry Follow up studies Auditory Threshold Middle Aged medicine.disease Dose–response relationship Neuroprotective Agents Otorhinolaryngology Toxicity Audiometry Pure-Tone Female business medicine.drug Follow-Up Studies |
| Zdroj: | The Laryngoscope. 114(9) |
| ISSN: | 0023-852X |
| Popis: | Ototoxicity is a common side effect of high-dose cisplatin treatment. Thiol-containing chemoprotectors ameliorate cisplatin ototoxicity under experimental conditions. The trial was initiated to test the efficacy of amifostine protection in high-dose cisplatin treatment (125-150 mg/m) for metastatic malignant melanoma, to correlate the ototoxic outcome with cisplatin pharmacokinetics, and to evaluate the importance of using a selective analytical method for the quantification of cisplatin.Prospective study of 15 patients with stage IV malignant melanoma.Clinical follow-up of therapeutic response, pure-tone audiometry, and analysis of cisplatin and its monohydrated complex in blood ultrafiltrate by liquid chromatography with postcolumn derivatization were performed. Ultrafiltered blood platinum was analyzed by inductively coupled plasma mass spectrometry.Ototoxicity and gastrointestinal toxicity were the most prominent side effects. Three patients ultimately required hearing aids. All patients had audiometric changes at one or more frequencies after the second treatment course, and all but one patient reported auditory symptoms. No correlation was found between hearing loss and blood cisplatin pharmacokinetics. Platinum levels determined by inductively coupled plasma mass spectrometry were higher than total platinum levels calculated from cisplatin and monohydrated complex concentrations obtained by liquid chromatography analysis.Ototoxicity was unacceptable despite amifostine treatment. Cisplatin pharmacokinetics during the first treatment course were not predictive of hearing loss. Amifostine caused a lowering of dose-normalized area under the concentration-time curve for cisplatin and monohydrated complex. Use of the unselective inductively coupled plasma mass spectrometry analysis leads to an overestimation of active drug. Selective analysis of cisplatin is especially important when evaluating cisplatin pharmacokinetics during chemoprotector treatment. |
| Databáze: | OpenAIRE |
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