Experience with bleomycin, ifosfamide, and cisplatin in primary and recurrent cervical cancer

The unfavorable prognosis for patients with advanced and bulky early stage cancer of the cervix may be improved by initial neoadjuvant cytoreductive chemotherapy. In a phase II study using ifosfamide in combination with cisplatin/bleomycin (BIP) in advanced and recurrent cervical cancer, we demonstrated a response rate of 69%. To determine whether this high response rate was a result of patient selection, and to assess the influence of combination chemotherapy on survival in patients with recurrent disease, a retrospective analysis of five phase II studies of bleomycin, ifosfamide, and cisplatin combinations was performed. The type of chemotherapy regimen (BIP v others) was the most significant factor in determining the likelihood of response. Combination chemotherapy did not appear to confer a survival advantage in patients with recurrent disease. The BIP regimen produced rapid responses with acceptable toxicity, and had potential for use as neoadjuvant therapy prior to radical radiotherapy in patients with advanced and bulky early stage disease. In an initial pilot study of this approach, 13 of 19 patients (68%) with primary inoperable disease had significant tumor regression prior to radical local radiotherapy. Interim analysis of the first 66 patients entered into a randomized study evaluating this approach has shown complete clinical tumor resolution after radical radiotherapy in 24 of 32 patients (75%) treated with up to three cycles of BIP prior to radiotherapy compared with 19 of 34 patients (56%) treated with radiotherapy alone. There has been no evidence that neoadjuvant chemotherapy enhances the acute toxic effects of pelvic radiotherapy. Therefore, this approach has potential to improve therapeutic outcome in patients with poor-prognosis primary disease.