title: Phase III double-blind, placebo-controlled, prospective randomized trial of adjuvant tamoxifen vs. tamoxifen and fenretinide in postmenopausal women with positive receptors (EB193): an intergroup trial coordinated by the Eastern Cooperative Oncology Group.
abstract: Fenretinide and tamoxifen have additive antitumor effects preclinically. We performed a randomized, placebo-controlled, double-blind adjuvant trial in breast cancer patients treated for 5 years with tamoxifen, with or without fenretinide. Between October 1995 and October 1999, 426 postmenopausal women with hormone receptor-positive breast cancer were randomized. Patients were monitored for efficacy and toxicity. Four hundred and nineteen patients were evaluable. The study was terminated early due to slow accrual. There were no significant differences between treatment groups in DFS, TTR or survival. More patients stopped treatment early on the fenretinide arm than on placebo (P = 0.02). Grade 3/4 toxicities, including visual problems and musculoskeletal complaints were more common in patients receiving fenretinide (P = 0.007). A Night Blindness Questionnaire was used to monitor nyctalopia, which was slightly, but not significantly, more common on fenretinide. In this underpowered study, no significant difference was observed in efficacy between treatment groups. This trial provides important toxicity information about fenretinide, a retinoid that has been used in the prevention setting, because it is the only placebo-controlled, double-blind randomized study ever performed.
authors.affiliation: Rush University Medical Center, 1725 W. Harrison St, Suite 809, Chicago, IL 60612, USA. ruta_d_rao@rush.edu
authors.forename: Ruta D
authors.initials: RD
authors.lastname: Rao
authors.forename: Melody A
authors.initials: MA
authors.lastname: Cobleigh
authors.forename: Robert
authors.initials: R
authors.lastname: Gray
authors.forename: Mark L
authors.initials: ML
authors.lastname: Graham
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: George Thomas
authors.initials: GT
authors.lastname: Budd
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: William C
authors.initials: WC
authors.lastname: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D017313:Fenretinide / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009755:Night Blindness / Q000139:chemically induced; D017698:Postmenopause; D011446:Prospective Studies; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D017313:Fenretinide