A phase I-II preoperative biomarker trial of fenretinide in ascitic ovarian cancer

Nicoletta Colombo, Franca Formelli, Maria Grazia Cantù, Gabriella Parma, Milena Gasco, Alessandra Argusti, Alfredo Santinelli, Rodolfo Montironi, Elena Cavadini, Laura Baglietto, Aliana Guerrieri-Gonzaga, Giuseppe Viale, Andrea Decensi

Research output: Contribution to journalArticlepeer-review


Purpose: To evaluate study feasibility, toxicity, drug concentrations, and activity of escalating doses of the synthetic retinoid fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] in ovarian cancer by measuring serum CA125 and cytomorphometric biomarkers in cancer cells collected from ascitic fluid before and after treatment. Methods: Twenty-two naive patients with ascitic ovarian cancer were treated with escalating doses of 4-HPR at 0, 400, 600, and 800 mg/d for 1 to 4 weeks before surgery. Changes in the proportion of proliferating cells expressed by Ki67 and computer-assisted cytomorphometric variables (nuclear area, DNA index, and chromatin texture) were determined in ascitic cells. Drug levels were measured by high-performance liquid chromatography. Results: Doses up to 800 mg/d were well tolerated, and no adverse reactions occurred. There was no effect of 4-HPR on changes in serum CA125, Ki67 expression, which were assessed in 75% of subjects, and cytomorphometric variables, which were assessed in 80% of subjects. Plasma retinol levels were significantly lower in affected women than healthy donors. 4-HPR plasma concentrations increased slightly with increasing doses and attained a 1.4 μmol/L concentration with 800 mg/d. Drug levels in malignant ascitic cells and tumor tissue were higher than in plasma but were 50 and 5 times lower, respectively, than in carcinoma cells treated in vitro with 1 μmol/L 4-HPR. Conclusions: Cell biomarkers can be measured in ascitic cells to assess drug activity. Under our experimental conditions, 4-HPR did not show activity in advanced ovarian cancer cells. However, clinical evidence supports further investigation of fenretinide for ovarian cancer prevention.

Original languageEnglish
Pages (from-to)1914-1919
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Issue number10
Publication statusPublished - Oct 2006

ASJC Scopus subject areas

  • Epidemiology
  • Oncology


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