High Dose Etretinate and Interferon-alpha: A Phase I Study in Squamous Cell Carcinomas and Transitional Cell Carcinomas

• Published in: Acta oncologica 1999, Vol.38 (5), p.613-618
• Main Authors: ROTH, A. D, MORANT, R, ALBERTO, P
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Squamous Cell - therapy; Carcinoma, Transitional Cell - therapy; Combined Modality Therapy; Dose-Response Relationship, Drug; Esophageal Neoplasms - therapy; Etretinate - administration & dosage; Etretinate - adverse effects; Etretinate - therapeutic use; Female; Head and Neck Neoplasms - therapy; Humans; Immunotherapy; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Keratolytic Agents - administration & dosage; Keratolytic Agents - adverse effects; Keratolytic Agents - therapeutic use; Lung Neoplasms - therapy; Male; Medical sciences; Middle Aged; Penile Neoplasms - therapy; Pharmacology. Drug treatments; Treatment Outcome; Urinary Bladder Neoplasms - therapy; Uterine Cervical Neoplasms - therapy
• ISSN: 0284-186X; 1651-226X
• DOI: 10.1080/028418699431203

Simultaneous exposure to retinoids and interferons can result in enhanced antiproliferative and differentiating effects on malignant lesions. We studied the toxicity and the potential efficacy of an association of high dose etretinate and Interferon-alpha (IFN-alpha) in squamous cell carcinomas of the lung, head and neck, the esophagus, cervix and the penis, as well as in transitional carcinomas of the bladder. The treatment consisted of etretinate (Tigason) 4 mg/kg/d on 2, 3, 4 and finally 5 consecutive days every other week and IFN-alpha (Roferon) 6 Mio IU sc. q.d. for 5 days every week. Of 24 patients enrolled, 23 were assessable for toxicity and 20 for response. With two occurrences of grade 3 cutaneous toxicity, the administration of etretinate (Tigason) 4 mg/kg/d on 5 consecutive days every other week and IFN-alpha (Roferon) 6 Mio IU sc. q.d. for 5 days every week was considered to be the MTD. Toxicity was mild otherwise, mostly at grades 1 and 2 level, causing fatigue, skin peeling and erythema, mucositis and cheilitis; 3 PR (partial response) and 8 SD (stable disease) were recorded. Of the responders, one patient had become resistant to cisplatin-based chemotherapy and the other two had at no time ever received systemic therapy. We conclude that the association of high doses of etretinate and IFN-alpha has moderate activity in squamous cell carcinomas, is well tolerated, and that IFN-alpha plays a role in the improved tolerance of the retinoid.