Article

Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002)

Division of Clinical Oncology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, 734-8551, Japan.
Gastric Cancer (Impact Factor: 4.83). 02/2011; 14(1):72-80. DOI: 10.1007/s10120-011-0009-5
Source: PubMed

ABSTRACT Irinotecan hydrochloride and S-1, an oral fluoropyrimidine, have shown antitumor activity against advanced gastric cancer as single agents in phase I/II studies. The combination of irinotecan and S-1 (IRI-S) is also active against advanced gastric cancer. This study was conducted to compare the efficacy and safety of IRI-S versus S-1 monotherapy in patients with advanced or recurrent gastric cancer.
Patients were randomly assigned to oral S-1 (80 mg/m² daily for 28 days every 6 weeks) or oral S-1 (80 mg/m² daily for 21 days every 5 weeks) plus irinotecan (80 mg/m² by intravenous infusion on days 1 and 15 every 5 weeks) (IRI-S). The primary endpoint was overall survival. Secondary endpoints included the time to treatment failure, 1- and 2-year survival rates, response rate, and safety.
The median survival time with IRI-S versus S-1 monotherapy was 12.8 versus 10.5 months (P = 0.233), time to treatment failure was 4.5 versus 3.6 months (P = 0.157), and the 1-year survival rate was 52.0 versus 44.9%, respectively. The response rate was significantly higher for IRI-S than for S-1 monotherapy (41.5 vs. 26.9%, P = 0.035). Neutropenia and diarrhea occurred more frequently with IRI-S, but were manageable. Patients treated with IRI-S received more courses of therapy at a relative dose intensity similar to that of S-1 monotherapy.
Although IRI-S achieved longer median survival than S-1 monotherapy and was well tolerated, it did not show significant superiority in this study.

0 Bookmarks
 · 
125 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Either palliative distal gastrectomy or gastrojejunostomy are the initial treatment options for locally advanced gastric cancer with outlet obstruction when curative-intent resection is not feasible. Since chemotherapy is the mainstay for unresectable gastric cancer, the clinical value of palliative distal gastrectomy is controversial. We retrospectively reviewed the clinical data of patients with gastric cancer with outlet obstruction treated at our institution between January 2002 and December 2012. We compared the clinical outcomes of palliative distal gastrectomy with those of gastrojejunostomy patients and the factors affecting overall survival were evaluated. Elective palliative distal gastrectomy and gastrojejunostomy were performed in 18 and 25 patients, respectively. The median overall survival times in the gastrojejunostomy and palliative distal gastrectomy groups were statistically equivalent at 8.8 and 8.3 months, respectively (P = 0.73), despite the more locally advanced tumors in the gastrojejunostomy as compared with the palliative distal gastrectomy group. A multivariate Cox regression analysis showed absence of postoperative chemotherapy and higher postoperative complication grade to be associated with worse clinical outcomes. Palliative distal gastrectomy offers neither survival nor palliative benefit as compared to gastrojejunostomy. Minimizing the morbidity of intervention for outlet obstruction, followed by chemotherapy, appears to be the optimal initial strategy for incurable gastric cancer with outlet obstruction.
    World Journal of Surgical Oncology 11/2014; 12(1):364. DOI:10.1186/1477-7819-12-364 · 1.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. The usual treatment of GC consists of surgery with additional adjuvant chemotherapy. In the present study, the feasibility and safety of adjuvant S-1 plus oxaliplatin (SOX) chemotherapy for patients with GC and the optimal dosage of S-1 were determined. Eligible patients were randomly assigned to either arm A (30 cases) receiving 70 mg/m(2) S-1 (in two seperate half doses) daily or arm B (30 cases) receiving 80 mg/m(2) S-1 (in two seperate half doses) daily. The S-1 was administered twice daily for 14 days followed by a 7-day rest period for the third week. A total of 130 mg/m(2) oxaliplatin was administered on day 1 every 3 weeks for each arm. The cumulative rates of the relative total administration dose of S-1 at 100% in the 6th treatment course was 71.4% [95% confidence interval (CI), 56.5-90.3%] in arm A, which was significantly higher than 21.4% (95% CI, 10.5-43.6%) in arm B (P=0.001). The most common grade 3/4 toxicities were neutropenia (19.6%), thrombocytopenia (19.6%) and vomiting (16.1%). Grade 3/4 thrombocytopenia was observed in 7.1% of patients in arm A and in 32.1% of patients in arm B (P=0.019). With regard to the adverse events induced by S-1 administration, the incidence of diarrhea (3.6 vs. 42.9%; P<0.001) was significantly higher in arm B than in arm A, as anticipated. Collectively, adjuvant SOX therapy for GC is feasible and safe, and when combined with 130 mg/m(2) oxaliplatin, 70 mg/m(2)/day S-1 appears to the optimal dose.
    Oncology letters 03/2015; 9(3):1451-1457. DOI:10.3892/ol.2014.2821 · 0.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite numerous advances in treatment options, advanced gastric cancer (AGC) remains a major public health issue and the leading cause of cancer-related deaths. Cisplatin is one of the most effective broad-spectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil (5FU)-based chemotherapy is generally used for treatment of patients with AGC. However, there is still no consensus on the best regimen for treating AGC. Recently, various new chemotherapeutic agents, including oral 5FU, taxanes, and irinotecan, have been identified as improving the outcomes for AGC when used as a single agent or in combination with non-platinum chemotherapy. Nonetheless, it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC. Accordingly, this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.
    World Journal of Gastroenterology 05/2014; 20(18):5396-5402. DOI:10.3748/wjg.v20.i18.5396 · 2.43 Impact Factor

Full-text (3 Sources)

Download
17 Downloads
Available from
Jun 4, 2014