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.