ENHANCED RADIOSENSITIZATION WITH INTERFERON-ALPHA-2B AND CISPLATIN INTHE TREATMENT OF LOCALLY ADVANCED CERVICAL-CARCINOMA

Purpose. To evaluate the efficacy and toxicity of interferon-alpha-2b (IFN-alpha) and cisplatin given concomitantly with radiation therapy ( RT) in the treatment of locally advanced cervical carcinoma. Materials and Methods. Twenty-one patients with stage bulky Ib-IIIb (Ib, 2; IIa , 2; IIb, 8; IIIb, 9) cervical carcinoma were treated with combined IF N-alpha (5 million IU) subcutaneously three times per week and cisplat in (25 mg/m(2)) iv infusion over 2 h weekly for 7 weeks, given concomi tantly with RT (4500 cGy of external beam plus 2 brachytherapy procedu res). Total radiation doses delivered ranged from 7500 to 9960 cGy (me dian, 9300 cGy). Follow-up ranged from 16 to 33 months (median, 25 mon ths). Results. The 2-year local control rate was 100%. The only sites of disease recurrence were distant. Freedom from distant metastases, d isease-free survival, and overall survival at 2 years was 76%. Late co mplication rates were high. Grade 4 rectosigmoid, bladder, and small b owel complication rates were 49, 18, and 23% at 2 years. Late toxicity was seen earlier than expected with rectosigmoid complications observ ed 5 to 11.5 months (median, 8 months) after completion of treatment. Conclusion. Combination IFN-alpha and cisplatin produced a marked effe ct of enhanced radiosensitization as evidenced by 100% local tumor con trol and high late normal tissue complication rates. Due to the unacce ptable late toxicity, its routine clinical use cannot be recommended. Further investigation is needed to determine whether a therapeutic win dow exists such that the use of lower doses of IFN-alpha, cisplatin, o r RT can increase tumor control with more acceptable normal tissue tox icity. (C) 1997 Academic Press.