fenretinide and Carcinoma--Basal-Cell

Topics: Anticarcinogenic Agents; Breast Neoplasms; Carcinoma, Basal Cell; Cell Differentiation; Cell Division; Clinical Trials as Topic; Female; Fenretinide; Head and Neck Neoplasms; Humans; Incidence; Leukoplakia, Oral; Models, Biological; Randomized Controlled Trials as Topic; Recurrence; Urinary Bladder Neoplasms

We are conducting three randomized studies (breast cancer, basal cell carcinoma, oral leukoplakia) and report our methodological approach and accrual here. The aim of the breast cancer study is prevention of a contralateral primary lesion in women already treated for breast cancer; the aim of the basal cell carcinoma study is prevention of recurrences or new occurrence after surgical resection; and the aim of the oral leukoplakia study is prevention of recurrences and new occurrence after CO2 laser resection. The studies were planned according to a randomized design with an intervention arm vs a no-treatment arm. Patients in the intervention group receive 4-HPR at a dose of 200 mg po. The duration of treatment is five years in the breast cancer study, and one year in the basal cell carcinoma and oral leukoplakia studies. The breast cancer study started in March 1987, closing accrual on July 31, 1993. A total of 2,972 patients entered the study; 2,849 were evaluable (1,422 in the 4-HPR group and 1,427 in the control group). Of 2,849 evaluable patients, 867 completed the first five years, 1,142 are still ongoing, and 840 patients have interrupted the study for various reasons. Follow-up is ongoing. The basal cell carcinoma study started in January 1990. As of January 1994, a total of 786 patients had entered the study; 760 were evaluable (363 in the 4-HPR group and 367 in the control group). Of 760 patients in the study, 568 completed the first year, 62 are ongoing and 130 discontinued for various reasons. The study is ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticarcinogenic Agents; Breast Neoplasms; Carcinoma, Basal Cell; Female; Fenretinide; Humans; Leukoplakia, Oral; Skin Neoplasms

Fenretinide or N-(4-hydroxyphenyl)retinamide is a vitamin A analogue synthesized in the United States in the late 1960s. This retinoid shows a preferential accumulation in breast instead of liver, is effective in the inhibition of chemically induced mammary carcinoma in rats, and has proved to be less toxic than many other vitamin A analogues. The Milan Cancer Institute has put a particular effort in this molecule in both the experimental and clinical fields. We have demonstrated, in animals and humans, that fenretinide induces a rapid reduction of retinol plasma concentration, that its blood levels remain constant during administration for as long as 5 years, and that the drug is able to accumulate in the human breast. To date, 2969 stage I breast cancer patients have been randomized to evaluate the efficacy of this retinoid to prevent contralateral new primaries, 709 subjects have been accrued in a prevention trial of basal cell carcinoma of the head and neck, and 153 patients entered a study the preliminary results of which already show the capability of fenretinide to prevent recurrences and new localizations of oral leukoplakia. Further studies on fenretinide will be aimed at evaluating its preventive efficacy in superficial bladder and prostate cancers and at exploring possible synergism with tamoxifen and interferons in breast cancer and skin cancer, respectively.

Topics: Anticarcinogenic Agents; Breast Neoplasms; Carcinoma, Basal Cell; Female; Fenretinide; Humans; Leukoplakia; Metabolic Clearance Rate; Mouth Neoplasms; Neoplasms; Vitamin A

We are conducting three randomized studies (breast cancer, basal cell carcinoma, oral leukoplakia) and report our methodological approach and accrual here. The aim of the breast cancer study is prevention of a contralateral primary lesion in women already treated for breast cancer; the aim of the basal cell carcinoma study is prevention of recurrences or new occurrence after surgical resection; and the aim of the oral leukoplakia study is prevention of recurrences and new occurrence after CO2 laser resection. The studies were planned according to a randomized design with an intervention arm vs a no-treatment arm. Patients in the intervention group receive 4-HPR at a dose of 200 mg po. The duration of treatment is five years in the breast cancer study, and one year in the basal cell carcinoma and oral leukoplakia studies. The breast cancer study started in March 1987, closing accrual on July 31, 1993. A total of 2,972 patients entered the study; 2,849 were evaluable (1,422 in the 4-HPR group and 1,427 in the control group). Of 2,849 evaluable patients, 867 completed the first five years, 1,142 are still ongoing, and 840 patients have interrupted the study for various reasons. Follow-up is ongoing. The basal cell carcinoma study started in January 1990. As of January 1994, a total of 786 patients had entered the study; 760 were evaluable (363 in the 4-HPR group and 367 in the control group). Of 760 patients in the study, 568 completed the first year, 62 are ongoing and 130 discontinued for various reasons. The study is ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anticarcinogenic Agents; Breast Neoplasms; Carcinoma, Basal Cell; Female; Fenretinide; Humans; Leukoplakia, Oral; Skin Neoplasms

Five patients with basal cell carcinoma received fenretinide. Two patients while receiving the drug had evidence of abnormal rod photoreceptor function that reversed rapidly on cessation of therapy. We speculate that fenretinide may interfere with the binding of vitamin A to opsin or with the transport of vitamin A.

Topics: Adult; Antineoplastic Agents; Carcinoma, Basal Cell; Clinical Trials as Topic; Dark Adaptation; Electroretinography; Female; Fenretinide; Humans; Male; Middle Aged; Photoreceptor Cells; Retina; Tretinoin; Vision Disorders