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: Ruta D Rao, Melody A Cobleigh, Robert Gray, Mark L Graham 2nd, Larry Norton, Silvana Martino, George Thomas Budd, James N Ingle, William C Wood
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 28 Suppl 1 Pg. S39-47 (Dec 2011) ISSN: 1559-131X [Electronic] United States
• PMID: 20878269 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Estrogen
• Receptors, Progesterone
• Tamoxifen
• Fenretinide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Breast Neoplasms (drug therapy, mortality)
• Chemotherapy, Adjuvant (methods)
• Double-Blind Method
• Female
• Fenretinide (administration & dosage, adverse effects)
• Follow-Up Studies
• Humans
• Middle Aged
• Night Blindness (chemically induced)
• Postmenopause
• Prospective Studies
• Receptors, Estrogen
• Receptors, Progesterone
• Tamoxifen (administration & dosage, adverse effects)