isotretinoin and Respiratory-Tract-Neoplasms

Retinoids can reverse neoplastic lesions and prevent second primary tumors in the aerodigestive tract. These effects are thought to be mediated by nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each receptor group including three subtypes (alpha, beta, and gamma). Previously, we found that RARbeta expression was suppressed in lung cancer. In this study, we investigated whether expression of RARbeta is modulated by chemopreventive intervention.. Using in situ hybridization, we analyzed RARbeta messenger RNA (mRNA) expression in bronchial biopsy specimens from heavy smokers, at baseline and after 6 months of treatment with 13-cis-retinoic acid (13-cis-RA) or placebo. Since we had previously detected RARbeta expression in 90% of bronchial specimens from nonsmokers, we considered loss of RARbeta mRNA expression in at least one of six biopsy specimens at baseline in this study to be aberrant.. RARbeta mRNA expression was aberrant in 30 (85.7%) of 35 subjects in the 13-cis-RA group and in 24 (72.7%) of 33 subjects in the placebo group. After 6 months of 13-cis-RA treatment, the number of subjects who were RARbeta positive in all six biopsy specimens increased from five of 35 to 13 of 35 (2.6-fold), so that the percentage of individuals with aberrant RARbeta expression decreased to 62.9% (22 of 35), which represents a statistically significant difference from baseline expression (two-sided P =.01). In the placebo group, no statistically significant difference in RARbeta expression was observed between baseline and 6 months. RARbeta expression was not related to current smoking status or reversal of squamous metaplasia.. These results indicate that RARbeta is an independent marker of response to 13-cis-RA and may serve as an intermediate biomarker in chemoprevention trials of upper aerodigestive tract cancers.

Topics: Adult; Aged; Anticarcinogenic Agents; Biomarkers; Biopsy; Bronchi; Cell Nucleus; Digestive System Neoplasms; Epithelium; Female; Gene Expression Regulation, Neoplastic; Humans; In Situ Hybridization; Isotretinoin; Male; Middle Aged; Receptors, Retinoic Acid; Respiratory Tract Neoplasms; RNA, Messenger; Smoking; Time Factors; Treatment Outcome

Topics: Carcinoma, Squamous Cell; Digestive System Neoplasms; Double-Blind Method; Follow-Up Studies; Head and Neck Neoplasms; Humans; Isotretinoin; Neoplasms, Second Primary; Respiratory Tract Neoplasms; Survival Analysis

Retinoic acid has been advocated for use in several premalignant and malignant epithelial lesions of the head and neck, including benign recurrent respiratory papillomatosis, with varying results. We describe a 24-year-old man with extensive tracheoesophageal and bronchoalveolar papillomatosis that degenerated into squamous cell carcinoma. Multiple endoscopic carbon dioxide laser excisions, at one point performed on a weekly basis, as well as a prolonged trial of interferon, failed to control the progression of his disease. Isotretinoin (13-cis-retinoic acid) therapy (1 mg/kg per day) was instituted, with dramatic clinical, radiographic, and functional improvement. The patient experienced no significant toxic effects and required no endoscopic procedures over a 6-month period. We propose that isotretinoin may be an effective adjuvant therapy for aggressive respiratory papillomatosis.

Topics: Administration, Oral; Adult; Carcinoma, Squamous Cell; Humans; Isotretinoin; Male; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Papilloma; Radiography; Respiratory Tract Neoplasms

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Neoplasm Recurrence, Local; Papilloma; Pilot Projects; Prospective Studies; Recombinant Proteins; Respiratory Tract Neoplasms; Severity of Illness Index; Treatment Outcome