The combination of 13-cis-retinoic acid and interferon α2a with radiation therapy in squamous cell carcinoma of the cervix

Kavanagh JJ, Lippman SM, Paredes-Espinoza M, Erikson AO, Delgadillo-Madrueño F, Paredes-Casillas P, Kudelka AP, Ki Hong W, Lotan R, Hittelman W, Ahn WS, Holdener E, Schleuniger U, Silva EG, Tornos CS, Krakoff IH. The combination of 13-cis-retinoic acid and interferon α2a with radiation therapy in squamous cell carcinoma of the cervix. Int J Gynecol Cancer 1996; 6: 439-444. Cervical cancer remains a major cause of cancer mortality and morbidity in many countries. Locally advanced disease often recurs despite many modifications of radiation therapy. Since the combination of interferon α2a and 13-cis-retinoic acid has resulted in a 50% response rate in locally advanced cancer of the cervix, we designed a study to define a tolerable dose of these biologics with standard radiation therapy. The tolerable therapy consisted of interferon α2a 6 MU subcutaneous 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 radiotherapy administered concurrently with interferon 3 MU administered 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 completion of irradiation. Hemorrhagic proctitis was the dose limiting toxicity. Among 23 patients evaluable for response to biologic therapy there 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 tolerable and appears active. A phase II study of this combination is warranted to confirm its activity and tolerability.