Multicenter Phase II Trial of S-1 Plus Cisplatin in Patients With Untreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Ajani, Jaffer A.; Lee, Fa Chyi; Singh, Deepak; Haller, Daniel G.; Lenz, Heinz Josef; Benson, Al B.; Yanagihara, Ronald; Phan, Alexandria T.; Yao, James C.; Strumberg, Dirk

doi:10.1200/jco.2005.04.2994

Cited by 83 publications

(57 citation statements)

References 14 publications

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“…Many patients received S-1 monotherapy or cisplatin-based regimens as first-line treatment. The response rates with first-line chemotherapies in our study were comparable to those reported previously (Sakata et al, 1998;Boku et al, 1999;Ohtsu et al, 2003;Ajani et al, 2006).…”

Section: Resultssupporting

confidence: 90%

“…Oxo is a gastrointestinal tract adverse effect modulator (Shirasaka et al, 1993). In Japan, S-1 as monotherapy or combined with cisplatin is a standard regimen for advanced GC (Sakata et al, 1998;Ajani et al, 2006). Boku et al (2007) reported the result of a randomised controlled trial showing that S-1 is a promising standard regimen as compared with 5-FU, and Narahara et al (2007) showed that S-1 plus cisplatin is superior to S-1 alone.…”

Section: Discussionmentioning

confidence: 99%

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Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Matsubara¹,

Nishina

Yamada³

et al. 2008

Br J Cancer

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Using laser-captured microdissection and a real-time RT -PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair crosscomplementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P ¼ 0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P ¼ 0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55 -3.67)), high DPD (HR: 2.04 (1.37 -3.02)), low EGFR (HR: 0.34 (0.20 -0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001 -1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC.

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Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Matsubara¹,

Nishina

Yamada³

et al. 2008

Br J Cancer

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“…The incidences of grades 3 and 4 toxic effects in our study are consistent with those reported previously for the same S-1 combination regimen (Ajani et al, 2006b;Inokuchi et al, 2006). When paclitaxel was administered every 3 weeks with or without 5-FU, non-haematological toxicity, apart from alopecia of grade 3 or higher, included neuropathy (0 -29%), myalgia (0 -27%), and nausea/vomiting (0 -7%) Yamada et al, 2001;Arai et al, 2003;Hokita et al, 2005;Kondo et al, 2005;Inokuchi et al, 2006).…”

Section: Discussionsupporting

confidence: 90%

“…An MST of at least 12 months and a TTP of at least 8 months would strongly suggest a significant advance in the treatment of advanced gastric cancer (Ajani et al, 2006b). In our phase I/II study, the response rate was 54.1% and the MST was 15.5 months.…”

Section: Discussionmentioning

confidence: 99%

“…Various chemotherapy regimens have been developed, but median survival in patients with unresectable or recurrent gastric cancer (or both) who receive chemotherapy remains less than 9 -12 months (Wils et al, 1991;Kim et al, 1993;Koizumi et al, 2003;Ohtsu et al, 2003;Ajani et al, 2006b). Randomised phase III studies of combination chemotherapy for unresectable advanced gastric cancer reported median survival times (MSTs) of 5 -9.6 months and overall response rates of 9 -46% (Webb et al, 1997;Vanhoefer et al, 2000;Ross et al, 2002;Ohtsu et al, 2003).…”

mentioning

confidence: 99%

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Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer

et al. 2006

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Both paclitaxel and S-1 are effective against gastric cancer, but the optimal regimen for combined chemotherapy with these drugs remains unclear. This phase I/II study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD), dose-limiting toxicity (DLT), and objective response rate of paclitaxel in combination with S-1. S-1 was administered orally at a fixed dose of 80 mg m À2 day À1 from days 1 to 14 of a 28-day cycle. Paclitaxel was given intravenously on days 1, 8, and 15, starting with a dose of 40 mg m À2 day À1 . The dose was increased in a stepwise manner to 70 mg m À2 . Treatment was repeated every 4 weeks unless disease progression was confirmed. In the phase I portion, 17 patients were enrolled. The MTD of paclitaxel was estimated to be 70 mg m À2 because 40% of the patients given this dose level (two of five) had DLT. The RD was determined to be 60 mg m À2 . In the phase II portion, 24 patients, including five with assessable disease who received the RD in the phase I portion, were evaluated. The median number of treatment courses was six (range: 1 -17). The incidence of the worst-grade toxicity in patients given the RD was 28 and 8%, respectively. All toxic effects were manageable. The response rate was 54.1%, and the median survival time was 15.5 months. Our phase I/II trial showed that S-1 combined with paclitaxel is effective and well tolerated in patients with advanced gastric cancer.

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Chemotherapy for advanced gastric cancer

Wagner¹,

Unverzagt²,

Grothe³

et al. 2010

Cochrane Database of Systematic Reviews

453

326

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Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU. All patients should be tested for their HER-2 status and trastuzumab should be added to a standard fluoropyrimidine/cisplatin regimen in patients with HER-2 positive tumours. Two and three-drug regimens including 5-FU, cisplatin, with or without an anthracycline, as well as irinotecan or docetaxel-containing regimens are reasonable treatment options for HER-2 negative patients.

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Multicenter Phase II Trial of S-1 Plus Cisplatin in Patients With Untreated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Abstract: S-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.

Cited by 83 publications

References 14 publications

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer

Chemotherapy for advanced gastric cancer

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