retinol-palmitate and Leukoplakia

Chemoprevention is a clinical strategy to block or reverse carcinogenesis before the development of invasive cancer. Studies of chemoprevention in the lungs and upper aerodigestive tract have relied on the field carcinogenesis hypothesis, which predicts that diffuse epithelial injury will result from exposure of that epithelium to carcinogens. This hypothesis is supported by the frequent occurrence of multiple primary tumors within the exposed field. In addition, the understanding of carcinogenesis as a multistep process supports the use of interventions in damaged epithelium before the development of clinically invasive cancer. Current efforts are focused on applying to chemoprevention studies the increasing knowledge of the molecular events in carcinogenesis. In our program, clinical trials in lung and head and neck chemoprevention have focused on individuals with evidence of field carcinogenesis, i.e., a history of previous epithelial cancer or the presence of premalignant lesions. These trials include studies to develop clinically applicable intermediate markers of carcinogenesis and large Phase III trials to evaluate the efficacy of the retinoid isotretinoin in preventing second primary tumors following head and neck or lung cancers.

Topics: Anticarcinogenic Agents; Diterpenes; Etretinate; Head and Neck Neoplasms; Humans; Isotretinoin; Leukoplakia; Lung Neoplasms; Mouth Neoplasms; Retinoids; Retinyl Esters; Vitamin A

Chemoprevention is a clinical strategy to block or reverse carcinogenesis before the development of invasive cancer. Studies of chemoprevention in the lungs and upper aerodigestive tract have relied on the field carcinogenesis hypothesis, which predicts that diffuse epithelial injury will result from exposure of that epithelium to carcinogens. This hypothesis is supported by the frequent occurrence of multiple primary tumors within the exposed field. In addition, the understanding of carcinogenesis as a multistep process supports the use of interventions in damaged epithelium before the development of clinically invasive cancer. Current efforts are focused on applying to chemoprevention studies the increasing knowledge of the molecular events in carcinogenesis. In our program, clinical trials in lung and head and neck chemoprevention have focused on individuals with evidence of field carcinogenesis, i.e., a history of previous epithelial cancer or the presence of premalignant lesions. These trials include studies to develop clinically applicable intermediate markers of carcinogenesis and large Phase III trials to evaluate the efficacy of the retinoid isotretinoin in preventing second primary tumors following head and neck or lung cancers.

Topics: Anticarcinogenic Agents; Diterpenes; Etretinate; Head and Neck Neoplasms; Humans; Isotretinoin; Leukoplakia; Lung Neoplasms; Mouth Neoplasms; Retinoids; Retinyl Esters; Vitamin A

Laryngeal leukoplakia can be a premalignant precursor of squamous cell carcinoma, is often tobacco-related and can usually be readily monitored by indirect laryngoscopy. One of the main motivations for using retinyl palmitate in patients with persistent leukoplakia was to avoid general anesthesia for elderly patients, who are considered to be high-risk patients when direct larynoscopy is required for possible tissue biopsy. Our study was the first to investigate the effectiveness and toxicity of high-dose retinyl palmitate in the treatment of laryngeal leukoplakia. Treatment was divided into two phases. In the first phase, all patients underwent induction therapy with 300,000 IU/day of retinyl palmitate for the 1st week, which was then adjusted up to 1,500,000 IU/day in the 5th week in patients with resistant lesions. Patients whose lesions progressed during this period were withdrawn from the study. In the second phase, patients whose lesions responded to treatment or remained stable were assigned to a maintenance therapy of 150,000 IU/day. Complete remission was observed in 15 of 20 patients (75% of cases). Partial response was seen in the remaining 5 patients, with 3 of the patients relapsing. The median duration of treatment and follow-up was 18 months (range, 12-24 months). These results indicate that retinyl palmitate has substantial activity in laryngeal leukoplakias. Since only minor side effects were seen, the medication is an excellent candidate as a preventive agent for laryngeal cancer.

Topics: Aged; Aged, 80 and over; Alcohol Drinking; Anticarcinogenic Agents; Biopsy; Carcinoma in Situ; Carcinoma, Squamous Cell; Disease Progression; Diterpenes; Female; Follow-Up Studies; Humans; Hyperplasia; Laryngeal Neoplasms; Laryngoscopy; Leukoplakia; Male; Middle Aged; Neoplasm Recurrence, Local; Precancerous Conditions; Remission Induction; Retinyl Esters; Smoking; Vitamin A

Leukoplakia, a white patch in the oral cavity or in the larynx that cannot be scraped off is a premalignant precursor of squamous cell carcinoma. It is tobacco-related and easily monitored. The rate of transformation of leukoplakia into invasive cancer is directly related to the degree of histologic abnormality. In the largest and longest study in the United States (mean follow-up, 7.2 years), the long-term transformation rate for dysplastic lesions was 36%. Surgical removal is considered the best therapy. However many patients operated on for oral leukoplakia later develop local relapses, new leukoplakias, or squamous cell carcinoma. Although leukoplakia lesions can show spontaneous regression, the response rate observed under treatment of retinoids is much greater.. In our study, high-dose retinyl palmitate was used for the first time on leukoplakias of the larynx. The study was conducted in two phases. In the first phase, all patients underwent induction therapy with a high dose of Retinyl Palmitate (A-Mulsin Hochkonzentrat, Mucos Pharma, Geretsried, Germany) 300.000 IU daily for the first week up to 1,500,000 IU daily in the fifth week. Patients whose lesions progressed during this period were withdrawn from the study. In the second phase, patients whose lesions responded to treatment or remained stable were then assigned to a maintenance therapy. The median duration of treatment was 104 days (range 15-272).. We observed a complete remission rate of 65% (20 out of 31 patients), a partial remission in 8 patients (26%) and a relaps in three patients (9%) during the next 15 months follow-up. Relapses were mainly seen in patients with a history of a carcinoma in situ or squamous cell carcinoma.. One of the main reasons for using retinyl palmitate in patients with larynx leukoplakia was to avoid general anesthesia in elderly patients who were considered as high risk patients for undergoing surgery. These results indicate that retinyl palmitate has substantial activity in larynx premalignancy. Because of its minor toxicity, it is an excellent candidate for a preventive agent for larynx cancer.

Topics: Aged; Aged, 80 and over; Anticarcinogenic Agents; Cell Transformation, Neoplastic; Diterpenes; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Laryngeal Neoplasms; Larynx; Leukoplakia; Male; Middle Aged; Retinyl Esters; Vitamin A