Phase II study of sequential cisplatin plus 5-fluorouracil/leucovorin (5-FU/LV) followed by irinotecan plus 5-FU/LV followed by docetaxel plus 5-FU/LV in patients with metastatic gastric or gastro-oesophageal junction adenocarcinoma.

PURPOSE: 5-Fluorouracil (5-FU) plus cisplatin (C) can be considered a standard option for advanced gastric cancer (AGC). Irinotecan (Ir) and docetaxel (D) are active agents with no complete cross-resistance with C and 5-FU. Concomitant combination of Ir or D with C and 5-FU is feasible, but with substantial toxicities. A different way to include all active agents in first-line treatment of AGC may be to use them sequentially. We aimed to evaluate the activity and the safety profile of sequential chemotherapy with 5-FU-based doublets with C, Ir and D in the first-line treatment of AGC.

METHODS: We conducted a phase II study of first-line sequential chemotherapy in metastatic GC. Treatment consisted of 3 cycles of C + infused 5-FU and leucovorin (CFL) followed by 3 cycles of Ir + 5-FU/LV (IrFL) followed by 3 cycles of D + 5-FU/LV (DFL). Primary end-point was response rate.

RESULTS: Forty-six patients were enrolled, median age 60 years, sites of disease (single/multiple) = 9/37, PS 0/1 = 27/19, gastric/gastro-oesophageal junction = 39/7. Median number of cycles was 9. Main grade 3-4 toxicities were neutropenia (37%), febrile neutropenia (2%), diarrhoea (4%), stomatitis (9%). Response rate after the planned 9 cycles was 45% (15 partial and 5 complete responses among 43 evaluable patients). Median PFS and OS: 6.8 and 11.1 months, respectively.

CONCLUSION: This sequential treatment is feasible with a favourable safety profile and produced encouraging results in terms of activity and efficacy.