Multicenter Phase III Comparison of Cisplatin/S-1 With Cisplatin/Infusional Fluorouracil in Advanced Gastric or Gastroesophageal Adenocarcinoma Study: The FLAGS Trial

Ajani, Jaffer A.; Rodriguez, W.; Bodoky, G.; Moiseyenko, Vladimir; Lichinitser, Mikhail; Gorbunova, Vera; Vynnychenko, I.; Garin, A.; Láng, István; Falcon, S.

doi:10.1200/jco.2009.25.4706

Cited by 511 publications

(374 citation statements)

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“…The median OS was 8.6 months in the cisplatin/S-1 arm and 7.9 months in the cisplatin/5-FU arm, showing no significant difference. However, significant safety advantages were observed with S-1/cisplatin for the rates of complicated neutropenia, stomatitis, hypokalemia, and treatment-related deaths [32]. Note that cisplatin was administered at a reduced dosage in the S-1 arm (75 mg/m 2 ) compared to the standard arm (100 mg/m 2 ), possibly explaining the more favorable toxicity profile with S1/cisplatin.…”

Section: Methodsmentioning

confidence: 99%

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

et al. 2013

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Section: Methodsmentioning

confidence: 99%

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

et al. 2013

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“…A second limitation is that this study enrolled only patients who had received preoperative S-1 plus cisplatin. S-1 plus cisplatin is one of the standard regimens for metastatic gastric cancer [18,19]. The validity of histological tumor response evaluation may vary with different chemotherapeutic regimens, and further studies are needed to investigate this point.…”

Section: Discussionmentioning

confidence: 99%

Validity of response assessment criteria in neoadjuvant chemotherapy for gastric cancer (JCOG0507-A)

et al. 2013

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Background Neoadjuvant chemotherapy may improve outcomes in gastric cancer. Tumor responses can be evaluated with RECIST, Japanese Classification of Gastric Carcinoma (JCGC), and histological criteria. These approaches have not yet been compared. Methods We analyzed two phase II trials of neoadjuvant chemotherapy using S-1 plus cisplatin. JCOG0210 included patients with linitis plastica and large ulcero-invasive tumors, whereas JCOG0405 comprised those with paraaortic or bulky lymph node metastases. Radiologic evaluations were conducted using RECIST in JCOG0405 and JCGC criteria in JCOG0210, because the latter included many patients without measurable lesions. A histological responder was defined as a patient in whom one third or more of the tumor was affected. The hazard ratios (HR) for death between responders and non-responders and response rate differences between short-and long-term survivors were estimated. Results In JCOG0210 (n = 49), HR was 0.54 in JCGC responders (P = 0.059) and 0.40 in histological responders (P = 0.005). The difference in response rates between short-and long-term survivors using histological criteria (34 %, P = 0.023) was greater than that using JCGC criteria (24 %, P = 0.15). In JCOG0405 (n = 51), HR was 0.67 in RECIST responders (P = 0.35) and 0.39 in histological responders (P = 0.030). In short-and long-term survivors, respectively, RECIST response rates were 62 and 67 % (P = 0.77), whereas histological response rates were 33 and 63 % (P = 0.048). Conclusions Histological criteria showed higher response assessment validity than RECIST or JCGC criteria and yielded the best surrogate endpoint for overall survival.

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“…Combination chemotherapy containing fluoropyrimidine plus platinum is globally recognized as the standard firstline treatment in MRGC [17][18][19][20][21]. Based on two recent phase III trials [4,5], second-line chemotherapy is currently considered a standard of care in MRGC patients after first-line therapy failure.…”

Section: Discussionmentioning

confidence: 99%

Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy after failure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival

Kang

et al. 2012

Gastric Cancer

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Background The aim of this study was to evaluate the activity and safety of the combination chemotherapy of 5-fluorouracil (5-FU), leucovorin, and irinotecan (FOLFIRI regimen) after failure of fluoropyrimidine, platinum, and taxane in gastric cancer (GC) and to evaluate the prognostic factors for survival. Methods Patients received biweekly FOLFIRI chemotherapy as third-line treatment. The FOLFIRI-1 consisted of irinotecan (180 mg/m 2 in a 2-h infusion) on day 1, and then leucovorin (200 mg/m 2 in a 2-h infusion) and 5-FU (a 400 mg/m 2 bolus, followed by 600 mg/m 2 in a 22-h continuous infusion) on days 1 and 2. FOLFIRI-2 consisted of irinotecan (180 mg/m 2 in a 2-h infusion) on day 1, and then leucovorin (400 mg/m 2 in a 2-h infusion) and 5-FU (a 400 mg/m 2 bolus, followed by 2400 mg/m 2 in a 46-h continuous infusion) on day 1. Results A total of 158 patients were included. The overall response rate was 9.6 % in patients with measurable lesions. The median progression-free survival (PFS) and overall survival (OS) were 2.1 months [95 % confidence interval (CI), 1.7-2.5] and 5.6 months (95 % CI, 4.7-6.5), respectively. The major grade 3/4 toxicity was myelosuppression (36.7 %). Good performance status (PS), fewer metastatic sites, and longer duration from the first-line to third-line chemotherapy were independent prognostic factors affecting both PFS and OS. Conclusions The FOLFIRI regimen showed antitumor activity and tolerable toxicity profiles against advanced GC in the third-line setting. Patients with good PS, fewer metastatic sites and longer previous treatment duration might have the maximal benefit from third-line chemotherapy.

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Multicenter Phase III Comparison of Cisplatin/S-1 With Cisplatin/Infusional Fluorouracil in Advanced Gastric or Gastroesophageal Adenocarcinoma Study: The FLAGS Trial

Abstract: Cisplatin/S-1 did not prolong OS of patients with advanced gastric or gastroesophageal adenocarcinoma compared with cisplatin/infusional fluorouracil, but it did result in a significantly improved safety profile.

Cited by 511 publications

References 21 publications

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

Optimal chemotherapy for advanced gastric cancer: is there a global consensus?

Validity of response assessment criteria in neoadjuvant chemotherapy for gastric cancer (JCOG0507-A)

Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy after failure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival

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