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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

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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.

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Author information

Authors and Affiliations

  1. Rush University Medical Center, 1725 W. Harrison St, Suite 809, Chicago, IL, 60612, USA

    Ruta D. Rao & Melody A. Cobleigh

  2. Dana Farber Cancer Institute, Boston, MA, USA

    Robert Gray

  3. Waverly Heme Onc, Cary, NC, USA

    Mark L. Graham II

  4. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Larry Norton

  5. The Angeles Clinic and Research Institute, Santa Monica, CA, USA

    Silvana Martino

  6. Cleveland Clinic Foundation, Cleveland, OH, USA

    George Thomas Budd

  7. Mayo Clinic, Rochester, MN, USA

    James N. Ingle

  8. Emory University, Atlanta, GA, USA

    William C. Wood

Authors
  1. Ruta D. Rao
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  2. Melody A. Cobleigh
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  3. Robert Gray
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  4. Mark L. Graham II
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  5. Larry Norton
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  6. Silvana Martino
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  7. George Thomas Budd
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  8. James N. Ingle
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  9. William C. Wood
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Corresponding author

Correspondence to Ruta D. Rao.

Additional information

This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M.D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA47559, CA07968, CA04919, CA25224, and CA37404 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

Study has also been published in abstract form: Cobleigh M, Gray R, Graham M, et al.: Fenretinide (FEN) vs. placebo in postmenopausal breast cancer patients receiving adjuvant tamoxifen (TAM), an Eastern Cooperative Oncology Group Phase III Intergroup Trial (EB193, INT-0151). Proc Am Soc Clin Oncol, 2000 (abstr).

Appendix: Night Blindness Questionnaire

Appendix: Night Blindness Questionnaire

Initially, the NBQ consisted of the 6 questions below. Patients could answer TRUE or FALSE to each. In 1996, items 1 and 3 were dropped.

  1. 1.

    I see better in normal daylight than in the evening.

  2. 2.

    I don’t adapt easily when going from a bright area to a dim one (for example, when driving into a tunnel during the daylight or going into a movie theater when a film is being shown).

  3. 3.

    I see poorly in the dark (for example, when getting up at night to go to the bathroom or looking for a light switch in the basement).

  4. 4.

    I have difficulty driving at night.

  5. 5.

    When I am in dim light, I can’t distinguish the outlines of objects well.

  6. 6.

    When I pass from a dimly lit room or place to a strongly lit one, I am dazzled (for example, when leaving a tunnel or leaving a subway station during daylight).

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Rao, R.D., Cobleigh, M.A., Gray, R. et al. 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. Med Oncol 28 (Suppl 1), 39–47 (2011). https://doi.org/10.1007/s12032-010-9682-1

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  • DOI: https://doi.org/10.1007/s12032-010-9682-1

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