1. ¹MRC Cancer Cell Unit and Cancer Research UK Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge CB2 2XZ, UK
2. ²Allergan Ltd, High Wycombe, Bucks HP12 3SH, UK
3. ³Allergan Inc., Irvine, CA 92713-9534, USA
4. ⁴Allergan SA, Mougins 06251, France
5. ⁵Cancer Research UK Medical Oncology Unit, Churchill Hospital, Oxford OX3 7LJ, UK
6. ⁶Centre for Cancer Treatment, Mount Vernon Hospital, Middlesex HA6 2RN, UK

Correspondence: Dr PH Jones, E-mail: phj20@cam.ac.uk

Received 14 January 2003; Revised 28 April 2003; Accepted 26 May 2003.

Abstract

Tazarotene is an acetylenic retinoid which is metabolised to tazarotenic acid and which binds selectively to the retinoid receptors RAR and RAR. 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.