This Article Full Text Full Text (PDF) Perspective on this Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by William, W. N. Articles by Papadimitrakopoulou, V. A. Search for Related Content PubMed PubMed Citation Articles by William, W. N., Jr. Articles by Papadimitrakopoulou, V. A. Related Collections Clinical Intervention Clinical Intervention: Early-Phase (I/II) Clinical or Translational Trials Clinical Intervention: Intraepithelial Neoplasia/Premalignancy

High-Dose Fenretinide in Oral Leukoplakia

Authors' Affiliations: Departments of ¹ Thoracic/Head and Neck Medical Oncology, ² Biostatistics, ³ Clinical Cancer Prevention, and ⁴ Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Vassiliki A. Papadimitrakopoulou, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 432, Houston, TX 77030. Phone: 713-792-6363; Fax: 713-792-1220; E-mail: vpapadim{at}mdanderson.org.

We previously showed that low-dose fenretinide (200 mg/d) had limited activity in retinoid-resistant oral leukoplakia (34% response rate) possibly because serum drug levels were insufficient to induce retinoid receptor–independent apoptosis. Therefore, we designed the single-arm phase II trial reported here to investigate whether higher-dose fenretinide would improve leukoplakia response over that of our previous study. Leukoplakia patients received fenretinide (900 mg/m² twice daily) in four 3-week cycles (1 week on drug followed by 2 weeks off). At week 12, clinical responses were determined and blood samples were collected for serum drug level assessments. A planned interim futility analysis led to early trial closure after the initial 15 (of 25 planned) patients because only 3 (20%) had a partial response (stopping rule: 4 responses in first 16 patients). Fenretinide was well tolerated—only one grade 3 adverse event (diarrhea) occurred. Serum fenretinide levels changed from 0 (baseline) to 0.122 ± 0.093 µmol/L (week 12). In correlative in vitro studies, high-dose fenretinide inhibited the growth of head and neck cancer cells more and oral leukoplakia cells less than did lower doses of fenretinide. This result is consistent with our clinical finding that high-dose fenretinide did not improve on the historical response rate of lower-dose fenretinide in our previous oral leukoplakia trial.

Key Words: oral cancer • fenretinide • oral premalignant lesion • leukoplakia • chemoprevention

This article has been cited by other articles:

				F. Formelli, E. Cavadini, V. Appierto, P. Tiberio, R. Grigolato, F. Chiesa, N. Tradati, and S. Persiani Comment re: Continuous Rather than Intermittent Administration of Fenretinide in Leukoplakia Cancer Prevention Research, March 1, 2009; 2(3): 281 - 281. [Full Text] [PDF]

				S. J. Freemantle, Y. Guo, and E. Dmitrovsky Retinoid Chemoprevention Trials: Cyclin D1 in the Crosshairs Cancer Prevention Research, January 1, 2009; 2(1): 3 - 6. [Full Text] [PDF]