title: A phase I trial of bexarotene in combination with docetaxel in patients with advanced solid tumors.
abstract: BACKGROUND
  The purpose of this study was to identify dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of docetaxel with a fixed-dose of bexarotene.
  
  
  METHODS
  This was a phase I, single-center and open-label trial of dose-escalating docetaxel with a fixed-dose oral bexarotene. Successive cohorts of 3 patients (pts), with confirmed solid tumors refractory to standard therapy or for whom no standard therapy existed, received fixed-dose oral bexarotene (400 mg/m(2) daily) with escalating doses of docetaxel weekly (25, 30, or 35 mg/m(2)) for 3 weeks on a 4-week cycle. Cohorts were expanded to 6 pts if a DLT was noted. The MTD was determined based on the occurrence of DLT in at least 2 of 6 pts during the first cycle.
  
  
  RESULTS
  Nineteen pts were enrolled. Seven pts were treated at 25 mg/m(2), 6 at 30 mg/m(2), and 6 at 35 mg/m(2) of docetaxel. The MTD for docetaxel was 30 mg/m(2) with 400 mg/m(2) of daily bexarotene. Hypothyroidism, hypertriglyceridemia, and fatigue were common toxicities. Three pts developed pulmonary toxicity (possible radiation recall pneumonitis [n = 2] and pulmonary hypertension because of tumor emboli [n = 1]). Two pts withdrew consent because of Grade 3 fatigue. Ten of 19 pts were noted to have stable disease and received more than 2 cycles of therapy. Of the 10 pts with stable disease, 5 had non-small-cell lung cancer (NSCLC), and of those 5 pts, 1 had a partial response that persisted for eight cycles. conclusion: The MTD of docetaxel was 30 mg/m(2) in combination with daily bexarotene at 400mg/m(2). Careful monitoring may be indicated in pts with previously irradiated lung tumors.
authors: FDA, Office of Oncology Drug Products, Silver Spring, MD, USA. smunshimalik@aol.com
authors: Shakun M
authors: SM
authors: Malik
authors: Brian
authors: B
authors: Collins
authors: Michael
authors: M
authors: Pishvaian
authors: Pari
authors: P
authors: Ramzi
authors: John
authors: J
authors: Marshall
authors: Jimmy
authors: J
authors: Hwang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077610:Bexarotene; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D043823:Taxoids; D013764:Tetrahydronaphthalenes; D000077143:Docetaxel; D000077610:Bexarotene