Randomized phase II trial of first-line treatment with tailored irinotecan and S-1 therapy versus S-1 monotherapy for advanced or recurrent gastric carcinoma (JFMC31-0301)

Abstract

Objective: The pharmacokinetics of irinotecan vary markedly between individuals. This study sought to compare tailored irinotecan plus S-1 therapy with S-1 monotherapy for the treatment of patients with advanced/recurrent gastric cancer. Methods:Patients with advanced/recurrent gastric cancer were randomized to receive tailored irinotecan plus S-1 (arm A) or S-1 alone (arm B). Arm A received S-1 (80−120 mg/m 2 /day) for 14 days, with irinotecan on days 1 and 15. The initial irinotecan dose of 75 mg/m 2 (Level 0) was adjusted for toxicity during the previous course. In arm B, S-1 (80−120 mg/day) was administered alone for 28 days, followed by 14 days without therapy.Results: Ninety-five patients were randomized (48 to arm A and 47 to arm B). The response rate of the primary tumor (Japanese criteria) was 25.0% in arm A (12/48) and 14.9% in arm B (7/47), while the response rates according to Response Evaluation Criteria In Solid Tumors (RECIST) were 27.8% (10/36) versus 21.9% (7/32).Hematological toxicity, anorexia, and diarrhea were significantly more common in arm A, but both arms had similar grade 3−4 toxicities. Conclusion:These findings suggest the usefulness of tailored irinotecan plus S-1 therapy for gastric cancer.

Overall survival benefits for irinotecan‐containing regimens as first‐line treatment for advanced gastric cancer: An updated meta‐analysis of ten randomized controlled trials

“…With regard to the chemotherapy used, the combined regimens of irinotecan differed between included studies; however, all studies used irinotecan-based doublet therapy, and combined drugs included docetaxel, 25 cisplatin, 22,39 oxaliplatin, 28 S-1 23,24,27 or 5-FU. 26,37,38 In addition, the controlled groups in trials were also different; three trials [22][23][24] used monotherapy as controlled group, whereas the others [25][26][27][28][37][38][39] used combination therapy as controlled group.…”

“…26,37,38 In addition, the controlled groups in trials were also different; three trials [22][23][24] used monotherapy as controlled group, whereas the others [25][26][27][28][37][38][39] used combination therapy as controlled group. Therefore, we did subgroup analysis based on the controlled therapy and found that for each of these patient subsets, irinotecan-containing chemotherapy had slightly better efficacy than monotherapy (HR ¼ 0.88, 95% CI ¼ 0.77-1.00) or nonirinotecan-containing combination therapy (HR ¼ 0.83, 95% CI ¼ 0.71-0.96).…”

“…Four additional conference abstracts were located as a result of hand searching. Finally, a total of ten publications were included in the review; these publications are related to six clinical trials reported in the full-text publications [22][23][24][37][38][39] and four conference abstracts. [25][26][27][28] The total number of patients randomly assigned in these trials was 1,837, with 786 in the irinotecan-containing chemotherapy arm and 1,051 in the nonirinotecan-containing chemotherapy arm.…”

“…[22][23][24][25][26][27][28] As a result, we systematize the available information to perform an updated meta-analysis of all RCTs on irinotecan-containing versus nonirinotecan-containing chemotherapies in AGC and to analyze and examine the survival benefits and the adverse reactions with irinotecan-containing chemotherapy.…”

Docetexal plus S-1 Versus Oxaliplatin plus S-1 for First-Line Treatment of Patients with Advanced Gastric Cancer: A Retrospective Study

“…S-1 is a 1:0.4:1 molar ratio mixture of tegafur and 2 5-FU-modulating substances: gimeracil (5-chloro-2, 4-dihydroxy-pyrimidine) and oteracil (potassium oxonate) [5]. The RR of S-1 as a single agent was promising at around 32% in gastric cancer [6,7,8]. In the FLAGS trial, S-1 demonstrated a similar efficacy and better toxicity profile compared to infusional 5-FU.…”