Combination chemotherapy with 254-S, ifosfamide, and peplomycin for advanced or recurrent cervical cancer.

Abstract

Based on the fact that combination chemotherapy with cisplatin, ifosfamide, and bleomycin generated a 69% response rate in patients with recurrent cervical cancer; that 254-S (a cisplatin analogue) monotherapy generated a 46.3% response rate for cervical cancer, which was higher than those generated by cisplatin and carboplatin in historic comparison; and that peplomycin is a bleomycin analogue with improved pulmonary toxic effects, a combination regimen with 254-S, ifosfamide, and peplomycin was evaluated in an animal experiment and a clinical study in patients with advanced or recurrent cervical cancer with an expectation that the regimen might show a higher efficacy than 254-S monotherapy and the combination regimen including cisplatin. In the clinical testing, 254-S was administered intravenously (IV) at 80-100 mg/m2, ifosfamide was administered IV at 1500 mg/patient for 5 days, and peplomycin was administered intramuscularly at 5 mg/patient for 6 days. This treatment was repeated every 4 weeks. As a result, this regimen showed additive or synergistic antitumor effects in mice receiving B16 melanoma transplants. In the clinical study, 83.8% and 60.9% response rates were obtained in 37 previously untreated patients with Stage III or IV cervical cancer and 23 with recurrent cervical cancer, respectively. The dose-limiting factor was bone marrow toxic effects, which were tolerable. The other toxic effects were mild, and there were no deaths. From these results, this combination regimen was thought worthy of evaluation in a Phase III comparative study in patients with advanced or recurrent cervical cancer.