THE COMBINATION OF 13-CIS-RETINOIC ACID AND INTERFERON ALPHA-2A WITH RADIATION-THERAPY IN SQUAMOUS-CELL CARCINOMA OF THE CERVIX

Cervical cancer remains a major cause of cancer mortality and morbidit y in many countries. Locally advanced disease often recurs despite man y modifications of radiation therapy. Since the combination of interfe ron alpha 2a and 13-cis-retinoic acid has resulted in a 50% response r ate in locally advanced cancer of the cervix, we designed a study to d efine a tolerable dose of these biologics with standard radiation ther apy. The tolerable therapy consisted of interferon alpha 2a 6 MU subcu taneous daily and 13-cis-retinoic acid orally 1 mg kg(-1) day(-1) for 8 weeks prior to the initiation of irradiation. This was followed by r adiotherapy administered concurrently with interferon 3 MU administere d three times per week and 13-cis-retinoic acid 0.5 mg kg(-1) day(-1). This dose of the biologics was continued for 4 weeks after the comple tion of irradiation. Hemorrhagic proctitis was the dose limiting toxic ity. Among 23 patients evaluable for response to biologic therapy ther e were nine responses (39%; 95% CI: 19-59%), with two being complete. Twenty-one patients were evaluable for efficacy of the bioradiotherapy . Eleven of 21 patients (52%; 95% CI: 20-85%) had a remission with the combined bioradiotherapy. This combination of bioradiotherapy is tole rable and appears active. A phase II study of this combination is warr anted to confirm its activity and tolerability.