Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel in gastric cancer with severe peritoneal metastasis (JCOG1108/WJOG7312G).

Abstract

80 Background: Oral fluoropyrimidine plus cisplatin is a standard treatment for advanced gastric cancer, but patients (pts) with severe peritoneal metastasis (PM) often cannot tolerate it. 5-fluorouracil (F), l-leucovorin (L) and paclitaxel (P) therapy (FLTAX) showed a promising activity in a feasibility study for such pts. We conducted a phase II/III (P-II/III) study comparing FLTAX vs FL. Methods: Eligibility criteria included: unresectable or recurrent gastric adenocarcinoma; 20–75 years; performance status (PS) 0–2; PM+; massive ascites and/or inadequate oral intake; no prior chemotherapy. Pts were randomly assigned to receive FL (F 600 mg/m2, L 250 mg/m2 on day1, 8, 15, 22, 29 and 36 q8w), or FLTAX (F 500 mg/m2, L 250 mg/m2, P 60 mg/m2 on day1, 8 and 15 q4w). In the P-II, decision to proceed to the P-III was made based on the median survival time (MST) in both arms and treatment success rate at week 8 with the threshold of 30% in the FLTAX. Primary endpoint of the P-III was overall survival. Results: A total of 101 pts (51 in FL and 50 in FLTAX) were enrolled to the P-II. Because of poor accrual, the protocol was amended for termination and the final analysis for the P-III was conducted. Treatment success rate at week 8 in FLTAX was 66.7% (95% confidence interval [CI] 51.6-79.6). MST was 6.1 M and 7.3 M for FL and FLTAX, respectively (HR 0.79; 80% CI 0.60-1.05; p = 0.14). MST was 2.5 M for FL and 5.1 M for FLTAX (HR 0.59; 95% CI 0.27-1.28) in pts with PS2 (n = 27); 6.5 M and 8.6 M, respectively (HR 1.02; 95% CI 0.62-1.68) in pts with PS0/1 (n = 74). Median progression-free survival was 1.9 M for FL and 5.4 M for FLTAX (HR 0.64; 95% CI, 0.43-0.96; p = 0.029). Common adverse events of grade ≥ 3 were neutropenia (FL 30.0%, FLTAX 20.8%), and anorexia (FL 47.1%, FLTAX 31.3%). Conclusions: Although this study could not show a survival benefit of FLTAX over FL for pts with severe PM, FLTAX would be an option with longer PFS and feasible toxicity, especially for pts with PS2. Clinical trial information: UMIN000010949.