Addition of intraperitoneal cisplatin and etoposide to first-line chemotherapy for advanced ovarian cancer: a randomised, phase 2 trial

Abstract

Background: We assessed the efficacy of adding intraperitoneal (IP) chemotherapy to standard first-line intravenous (IV) chemotherapy in epithelial ovarian cancer (EOC) patients.

Methods: Patients with stage IIIC-IV EOC who underwent optimal debulking surgery were randomly assigned to four cycles of weekly IP chemotherapy with cisplatin (50 mg/m²) and etoposide (100 mg/m²) followed by six cycles of IV chemotherapy every 3 weeks (IP/IV arm), or were administered IV chemotherapy alone (IV arm). The primary endpoint for this study was the 12-month non-progression rate (NPR).

Results: Between 4/2009 and 9/2015, 218 patients were randomised, of whom 215 initiated treatment. In the IP/IV arm, 90.6% of patients completed 4 cycles of IP chemotherapy. The 12-month NPRs were 81.9% and 64.2% in the IP/IV and IV groups, respectively (HR 0.48 (95% CI 0.27-0.82)). The median progression-free survival (PFS) was increased in the IP/IV arm compared with that in the IV arm (22.4 vs. 16.8 months; HR 0.66 (0.48-0.91)) and in a subgroup with no gross cytoreduction (31.1 vs. 16.8 months; HR 0.46 (0.26-0.82)). Similar findings were detected with regard to time to first subsequent anticancer therapy (TFST) (25.9 vs. 18.0 months; P = 0.009) and time to second subsequent anticancer therapy (TSST) (40.8 vs. 30.1 months; P = 0.042). Grade 3/4 leukopenia, anaemia and gastrointestinal events were more common in the IP/IV arm, but the treatment burden was considered acceptable.

Conclusions: IP chemotherapy prior to IV chemotherapy was associated with an increased 12-month NPR and a longer TSST than IV alone in patients with EOC, albeit with acceptable toxic effects. Long-term follow-up is warranted to identify the effects of IP therapy on overall survival.

Fig. 1

Trial profile

Fig. 2

Kaplan–Meier distribution of progression-free survival time. Patients in the IP/IV arm had improved PFS compared with those in the IV arm (P = 0.010; HR = 0.66; 95% CI, 0.48–0.91)

Fig. 3

Kaplan–Meier distribution of progression-free survival time in subgroup of patients with R0 resection (A), and of patients with residual disease 0.1–1 cm (B) in the whole abdomen after primary cytoreductive surgery