A Randomized Phase Iii Trial Of Cisplatin With Or Without S-1 In Patients With Figo Ivb, Recurrent, Or Persistent Cervical Cancer: An Asian Study.

5527 Background: A combination of S-1, an oral fluoropyrimidine, plus cisplatin has been used for advanced gastric cancer in Asia and EU, and lung cancer in Japan. It also evaluated in advanced or recurrent cervical cancer in a phase II setting. We conducted a randomized phase III trial to compare the efficacy and safety of S-1 plus cisplatin with those of cisplatin alone in recurrent or persistent after treatment and FIGO IVB cervical cancer patients. Methods: Stage IVB, recurrent or persistent cervical cancer patients aged ≥ 20 years, ECOG PS 0–1 and adequate organ function were randomly assigned (1:1) to receive S-1 (80–120 mg daily, according to BSA, day 1–14) plus cisplatin (50 mg/m 2 on day 1) (study group) or cisplatin alone (50 mg/m 2 on day 1) (control group) every 3 weeks. Treatment was continued until disease progression. In all, 360 patients (at least 296 events) with a hazard ratio (HR) for death of 0.72 were required for a two-sided alpha of 5% and power of 80% under 2 years of recruitment and 1.5 years of follow-up. Stratification factors included recurrence in previously irradiated field, previous platinum-based therapy, and institution. Primary endpoint was OS based on intent-to-treat principle, and secondary endpoints were PFS, overall response rate (ORR), and safety. Results: In all, 375 patients were assigned to the study (n = 189) and control (n = 186) groups. Rate of previous platinum-based therapy was 64%. The median survival time was 21.9 and 19.5 months (95% CI, 18.6–25.8 and 17.0–24.3) with the use of unstratified log-rank test in the study and control groups, respectively (log-rank P = 0.125; HR, 0.84; 95% CI, 0.67–1.05). Significant increases in median PFS (7.3 vs. 4.9 months; log-rank P < 0.001; HR, 0.62) and ORR (43.8 vs. 20.1%, P < 0.001) were observed in the study group. Adverse events (grade≥3) were frequent in the study group (80.9 vs. 41.7%) with neutropenia (52.7%), anemia (34.6%), and leukopenia (32.4%) being the most common events. Conclusions: Compared with cisplatin alone, S-1 plus cisplatin did not significantly improve OS but increased ORR, prolonged PFS, and had tolerable safety of patients with stage IVB, recurrent or persistent cervical cancer. Clinical trial information: NCT00770874.