text: A phase 1 study of tazarotene in adults with advanced cancer.
  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.
entities.id: T10 T11 T12 T13 T14 T1 T2 T3 T4 T5 T6 T7 T8 T9
entities.type: CHEMICAL CHEMICAL GENE-N GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
entities.text: tazarotenic acid tazarotene retinoid receptors RARbeta RARgamma Tazarotene tazarotene retinoid tazarotene retinoids acetylenic retinoid tazarotene tazarotene tazarotenic acid