Prognostic factors in platinum-resistant ovarian carcinoma treated with ifosfamide-etoposide

One hundred and seven patients (median age 56) with cisplatin-resistant ovarian carcinomas were included in a phase II study with ifosfamide (5 g/m2) and etoposide (300 mg/m2) every three weeks. The first 30 patients received a 5-day regimen: 100 mg/m2 etoposide (i.v.) repeated in three days followed by 1 g/m2 ifosfamide as a bolus dose in five days. Mesna 200 mg/m2 was given 0.4 and 8 hours after each ifosfamide infusion. The next 77 patients received a 1-day regimen: 300 mg/m2 etoposide for two hours and then 5 g/m2 ifosfamide together with 5 g/mg2 mesna in 3.000 ml Ringer solution for 24 hours followed by 1 g/m2 mesna i.v. in 100 ml Ringer solution for eight hours. Overall the objective response rate was 6.5% (all PR) and SD in 42% of patients with a median duration of six and four months, respectively. Median survival of the total group was seven and 12 months for the responders. One- and two-year overall survival was 32% and 6%, respectively. Toxicity was similar in both regimens except for significantly more nausea and vomiting (gr 3 and 4) in groups with the 1-day regimen. There were few serious effects and they were manageable. Multivariate analysis identified degree of differentiation and response to ifosfamide/etoposide as the two most powerful prognostic factors of overall survival (p=0.0004 and p=0.0018, respectively). In conclusion, the therapeutic index of ifosfamide/etoposide treatment was very low and in this subset of ovarian cancer patients with platinum resistance and should be abandoned.