title: Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer.
abstract: BACKGROUND
  Since the improvement of chemotherapy with safe molecules is needed for a better efficacy without supplementary toxicity, we investigated the feasibility and tolerability of the combination of docetaxel and curcumin, a polyphenolic derivative extracted from Curcuma longa root.
  
  
  RESULTS
  Fourteen patients were accrued in this open-label phase I trial. At the last dose level of curcumin, three dose-limiting toxicities were observed and two out of three patients at this dose level refused to continue treatment, leading us to define the maximal tolerated dose of curcumin at 8,000 mg/d. Eight patients out of 14 had measurable lesions according to RECIST criteria, with five PR and three SD. Some improvements as biological and clinical responses were observed in most patients.
  
  
  METHODS
  Patients with advanced or metastatic breast cancer were eligible. Docetaxel (100 mg/m(2)) was administered as a 1 h i.v. infusion every 3 w on d 1 for six cycles. Curcumin was orally given from 500 mg/d for seven consecutive d by cycle (from d-4 to d+2) and escalated until a dose-limiting toxicity should occur. The primary endpoint of this study was to determine the maximal tolerated dose of the combination of dose-escalating curcumin and standard dose of docetaxel chemotherapy in advanced and metastatic breast cancer patients. Secondary objectives included toxicity, safety, vascular endothelial growth factor and tumor markers measurements and assessment of objective and clinical responses to the combination therapy.
  
  
  CONCLUSIONS
  The recommended dose of curcumin is 6,000 mg/d for seven consecutive d every 3 w in combination with a standard dose of docetaxel. From the encouraging efficacy results, a comparative phase II trial of this regimen plus docetaxel versus docetaxel alone is ongoing in advanced and metastatic breast cancer patients.
authors.affiliation: Centre Jean Perrin, Division de Recherche Clinique, Université d'Auvergne, Centre d'Investigation Clinique, Clermont-Ferrand, France. Mathilde.Bayet-Robert@u-clermont1.fr
authors.forename: Mathilde
authors.initials: M
authors.lastname: Bayet-Robert
authors.forename: Fabrice
authors.initials: F
authors.lastname: Kwiatkowski
authors.forename: Marianne
authors.initials: M
authors.lastname: Leheurteur
authors.forename: Françoise
authors.initials: F
authors.lastname: Gachon
authors.forename: Eloïse
authors.initials: E
authors.lastname: Planchat
authors.forename: Catherine
authors.initials: C
authors.lastname: Abrial
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Mouret-Reynier
authors.forename: Xavier
authors.initials: X
authors.lastname: Durando
authors.forename: Chantal
authors.initials: C
authors.lastname: Barthomeuf
authors.forename: Philippe
authors.initials: P
authors.lastname: Chollet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D003474:Curcumin / Q000008:administration & dosage*; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D003474:Curcumin