A phase 1 study of tazarotene in adults with advanced cancer
| Autor: | Zhiling Yu, Diane D.-S. Tang-Liu, Philip H. Jones, G. J. S. Rustin, R D Burnett, Adrian L. Harris, P Nadolny, I Fainaru, Denis C. Talbot, Trivadi S. Ganesan, Patricia S. Walker |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Male Cancer Research Hypercalcaemia Maximum Tolerated Dose medicine.drug_class Mucocutaneous zone Cmax Antineoplastic Agents Biology Pharmacology Retinoids Clinical oral Pharmacokinetics Tazarotene Neoplasms medicine Humans Retinoid Dosing Aged Neoplasm Staging Dose-Response Relationship Drug tazarotenic acid Nicotinic Acids Middle Aged medicine.disease Oncology retinoid Area Under Curve Toxicity Female medicine.drug |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/sj.bjc.6601169 |
| Popis: | Tazarotene is an acetylenic retinoid which is metabolised to tazarotenic acid and which binds selectively to the retinoid receptors RARbeta and RARgamma. The safety, toxicity and pharmacokinetics of oral tazarotene were determined over 12 weeks of treatment in 34 patients with advanced cancer. Commonly seen toxicities were mucocutaneous symptoms, musculoskeletal pain and headache. Dose-limiting toxicities were hypercalcaemia, hypertriglyceridaemia and musculoskeletal pain. The maximum tolerated dose of tazarotene in this schedule is 25.2 mg day(-1). Plasma concentrations of tazarotenic acid were found to peak rapidly within 1-3 h of dosing and thereafter declined quickly. The C(max) and AUC values on day 0, and weeks 2 and 4 were similar indicating no drug accumulation. The dose-normalised C(max) and AUC values at different dose levels and different study days appeared to be similar indicating linear pharmacokinetics. No objective responses were seen, although stable disease was seen in six out of eight evaluable patients receiving the three highest dose levels of tazarotene (16.8, 25.2 or 33.4 mg day(-1)). We conclude that oral tazarotene is well tolerated when administered daily for 12 weeks, has a favourable toxicity profile compared with other retinoids and merits further investigation as an anticancer therapy. |
| Databáze: | OpenAIRE |
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