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Phase II Study of Fenretinide (NSC 374551) in Adults With Recurrent Malignant Gliomas: A North American Brain Tumor Consortium Study

From The University of Texas M.D. Anderson Cancer Center, Houston; The University of Texas Health Sciences Center at San Antonio, San Antonio, TX; University of California San Francisco, San Francisco; University of California Los Angeles, Los Angeles, CA; National Cancer Institute Cancer Therapy Evaluation Program, National Institutes of Health, Bethesda, MD; University of Michigan, Ann Arbor, MI; Dana Farber Cancer Institute, Boston, MA; University of Pittsburgh, Pittsburgh, PA; and University of Wisconsin, Madison, WI

Address reprint requests to Vinay K. Puduvalli, MD, Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston TX 77030; e-mail: vpuduval{at}mdanderson.org

PURPOSE: Fenretinide induces apoptosis in malignant gliomas in vitro. This two-stage phase II trial was conducted to determine the efficacy of fenretinide in adults with recurrent malignant gliomas.

PATIENTS AND METHODS: Twenty-two patients with anaplastic gliomas (AG) and 23 patients with glioblastoma (GBM) whose tumors had recurred after radiotherapy and no more than two chemotherapy regimens were enrolled. Fenretinide was given orally on days 1 to 7 and 22 to 28 in 6-week cycles in doses of 600 or 900 mg/m² bid.

RESULTS: Six of 21 (29%) patients in the AG arm and two of 23 (9%) patients in the GBM arm had stable disease at 6 months. One patient with AG treated at 900 mg/m² bid dosage had a partial radiologic response. Median progression-free survival (PFS) was 6 weeks for the AG arm and 6 weeks for the GBM arm. PFS at 6 months was 10% for the AG arm and 0% for the GBM arm. Grade 1 or 2 fatigue, dryness of skin, anemia, and hypoalbuminemia were the most frequent toxicities reported. The trial was closed after the first stage because of the inadequate activity at the fenretinide doses used. The first-administration mean plasma C_max for fenretinide was 832 ± 360 ng/mL at the 600 mg/m² bid dosage and 1,213 ± 261 ng/mL at the 900 mg/m² bid dosage.

CONCLUSION: Fenretinide was inactive against recurrent malignant gliomas at the dosage used in this trial. However, additional studies using higher doses of the agent are warranted based on the tolerability of the agent and the potential for activity of a higher fenretinide dosage, as suggested in this trial.

Supported in part by grant Nos. CA62399, CA62422, CA62412, CA16672, CA62455, CA62426, UO1CA62407-08, UO1CA62405, UO1CA62399, UO1CA62421, MO1-RR00079, MO1-RR00633, MO1-RR00056, MO1-RR0865, MO1-RR00042, and MO1-RR03186 from the National Institutes of Health, Bethesda, MD.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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