Randomized phase II trial of irinotecan, leucovorin and 5-fluorouracil (ILF) versus cisplatin plus ILF (PILF) for advanced gastric cancer

Abstract

4580 Background: Irinotecan, in combination with 5-fluorouracil (FU) or cisplatin, clearly demonstrated efficacy against gastric cancer. We compared the combination of irinotecan, leucovorin and FU (ILF) with cisplatin plus ILF (PILF) as first-line chemotherapy in patients with advanced gastric cancer (AGC). Methods: Patients with chemotherapy-naïve, histologically-confirmed, metastatic gastric adenocarcinoma were randomized to receive irinotecan 150 mg/m2 on day 1, leucovorin 20 mg/m2 and a 22-h infusion of FU 1,000 mg/m2 on days 1 and 2 (ILF), or ILF plus cisplatin 30 mg/m2 on day 2 (PILF). Treatment was repeated every 2 weeks until disease progression, unacceptable toxicity, or patients’ refusal. Primary endpoint was response rate which assessed every 4 cycles of chemotherapy. With a single-stage phase II design, the required number of patients was at least 35 per each arm. Results: Of 91 patients registered, 46 patients were treated with ILF and 44 with PILF. For both arms, 635 chemotherapy cycles were delivered (median, 6 for ILF and 8 for PILF; p=0.46). Both ILF and PILF were generally well tolerated. However, PILF was associated with, although statistically insignificant, substantially more grade 3 or 4 toxicities than ILF (46% and 38%, respectively). In the ILF and PILF arm, 11% and 25% of patients, respectively, discontinued treatment because of toxicity. Treatment duration was similar for both arms (4.3 for ILF v 5.6 months for PILF; p=0.13). Four patients died during treatment: one in the ILF arm and 3 in the PILF arm. The objective response rate was 37% for both arms. Disease control (response plus stable disease) was achieved in 59% and 73% (p=0.02) of patients treated with ILF and PILF. There were no significant differences in therapeutic efficacy between ILF and PILF with respect to progression-free (4.8 v 6.2 months; p=0.60) and overall (10.9 v 10.4 months; p=0.93) survival. Conclusions: Both ILF and PILF appear to be active as first-line chemotherapy for AGC, with acceptable safety profiles. Given the comparable efficacy results, ILF could be a reasonable standard chemotherapy for untreated AGC patients. No significant financial relationships to disclose.