The role of ifosfamide and systemic therapy in the management of carcinoma of the cervix.

Nineteen single agents have activity in patients with advanced or recurrent carcinoma of the cervix. The agents that have attracted the greatest attention, however, are the platinum compounds and ifosfamide. Although most phase II trials combining these agents demonstrate activity but not relative merit, a recent phase III randomized trial shows that ifosfamide/cisplatin yields a superior response rate than cisplatin alone (33% v 19%, respectively). An ongoing randomized study is evaluating cisplatin/ifosfamide with or without bleomycin on the basis of a number of phase II reports suggesting a high order of activity for the three-drug combination. Randomized trials in less advanced disease demonstrate superior response rate, progression-free interval, and overall survival for concomitant chemoradiation in patients with stage IIIB to IVA disease. Regimens with demonstrated efficacy in this setting include hydroxyurea plus radiation and cisplatin/5-fluorouracil plus radiation. Of two randomized trials of cisplatin/ifosfamide/bleomycin followed by radiation versus radiation alone, the one completed study shows no overall advantage for the combined approach but does suggest an improved 32-month survival in patients with stage IIIB disease. The other trial is ongoing, with an early observation of a superior response rate with the combined approach. Current recommendations are to use ifosfamide/cisplatin as the treatment of choice for advanced or recurrent disease and concomitant chemoradiation with either hydroxyurea or cisplatin/5-fluorouracil for stage IIIB to IVA disease.