title: A pilot phase II trial of all-trans retinoic acid (Vesanoid) and paclitaxel (Taxol) in patients with recurrent or metastatic breast cancer.
abstract: OBJECTIVE
  We investigated a combination therapy with weekly paclitaxel and all trans-retinoic acid (ATRA) for tolerability, response to treatment, time to progression and survival in previously treated patients with metastatic or recurrent breast cancer. Our rationale was based on preclinical studies demonstrating potentiation of the cytotoxic effects of taxanes and induction of differentiation by ATRA.
  
  
  METHODS
  Seventeen patients with previously treated metastatic or recurrent breast cancer were enrolled to a regimen of all-trans retinoic acid (Vesanoid, tretinoin, Hoffman-La Roche, Inc.) 45 mg/m(2) PO daily for 4 days starting 2 days before a 1 h treatment with paclitaxel (Taxol, Bristol-Myers Squibb, Plainsboro, NJ) 80 mg/m(2) IV administered weekly for 3 weeks, repeated in 28 day cycles until disease progression or until no longer tolerated. Patients were evaluated for toxicity, response, time to progression and survival. Patients were primarily African American and Latino, representative of the population served by our Cancer Center.
  
  
  RESULTS
  The regimen was relatively well tolerated. There were nine grade 3 and one grade 4 toxic events. We administered 162 treatment cycles with a mean of 7.5 per patient (range 1-22, median 5). Three patients had a partial response (17.6%) and ten patients had stable disease (58.8%), with an overall clinical benefit of 76.4%. Median time to progression was 6.0 months (range 1-21, mean 7.7 months). Fourteen evaluable patients had a median survival of 16 months (range 1-68 months, mean 25.2 months).
  
  
  CONCLUSIONS
  The data suggest this is a well tolerated regimen with modest response rates but with time to progression and survival rates similar to those reported for paclitaxel alone and relatively high rates of stable disease in this sample of patients.
authors.affiliation: Department of Medicine, UMDNJ-New Jersey Medical School/University Hospital Cancer Center, Newark, NJ, USA.
authors.forename: Margarette
authors.initials: M
authors.lastname: Bryan
authors.forename: E Dianne
authors.initials: ED
authors.lastname: Pulte
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Toomey
authors.forename: Lillian
authors.initials: L
authors.lastname: Pliner
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: Tracie
authors.initials: T
authors.lastname: Saunders
authors.forename: Robert
authors.initials: R
authors.lastname: Wieder
mesh_terms: D001741:Black or African American; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000008:administration & dosage; D010865:Pilot Projects; D015996:Survival Rate; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D014212:Tretinoin; D017239:Paclitaxel