OBJECTIVES: Recently, interferon(IF) alpha2a and 13-cis retinoic acid(RA) have been known to have a significant antitumor activity on the squamous cell carcinoma of the uterine cervix. Thus we performed a pilot study to evaluate the clinical efficacy and tolerability of bioradiotherapy consisted of IF-alpha2a, 13-cis RA and radiotherapy in cervical cancer patients with primary bulky tumors. METHODS AND MATERIALS: 15 consecutive cervical cancer patients(stage IB2~IVA) with primary bulky tumors received IF-alpha2a(6x10(6) IU subcutaneous injection daily for 1 week, then 3x10(6) IU subcutaneous injection 3 times a week for 8 weeks), 13-cis RA(1 mg/Kg oral medication in two divided dose daily for initial 7 days, then 0.5 mg/Kg oral medication daily for 8 weeks) and radiotherapy concurrently as study group. Another 15 cervical cancer patients(stage IB2~IVB) with comparable primary bulky tumors were treated with standard radiotherapy as control group. RESULTS: Overall response rates(ORR) of all patients in study group and control group were 86.7%(CR; 20.0%) and 80.0%(CR; 6.7%), respectively(p>0.05). But we found that bioradiotherapy was significantly more effective compared to the standard radiotherapy for the control of primary bulky tumors of early stages(IB2~II)(ORR; 90.0% vs. 72.7%, p<0.05). 3 year-survival rates of all patients in study group and control group were 60% and 54%, respectively(p<0.05). Treatment modality and SCC antigen level had significant relationships with 3-year survival in univariate analysis(p<0.05), but stage, age, tumor size did not(p>0.05). In multivariate analysis, while stage, age, tumor size, SCC antigen level were not related with 3-year survival(p>0.05), only treatment modality showed significant relationship with 3-year survival(p<0.05). Major side effects of the bioradiotherapy were low grade fever (57%) and flu-like symptoms(46%). and tolerable in all patients. There was no toxicity of grade 3 or 4 during the bioradiotherapy. CONCLUSIONS: Our results suggested that bioradiotherapy was an active and tolerable therapy, comparing to the standard radiotherapy, especially for the localized bulky primary cervical tumor of early stages(IB2~II). Randomized prospective study in a large scale is feasible and needed in the future to confirm the role of the bioradiotherapy in the treatment of primary bulky cervical cancer, especially for the patients who cannot tolerate concurrent chemoradiation because of the toxicities of chemotherapy.