The influence of prior ramucirumab treatment on the clinical activity of FOLFIRI as third-line therapy in patients with metastatic gastric Cancer
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Purpose Few data described the activity of chemotherapy after ramucirumab plus paclitaxel progression in metastatic gastric cancer patients. The aim of this phase II study is to assess the efficacy and safety of the FOLFIRI regimen as a third-line of treatment. Methods The study enrolled patients with histologically proven metastatic gastric cancer or gastroesophageal junction carcinoma whose disease had progressed after ramucirumab-based second line of treatment. Treatment consisted of biweekly irinotecan 150 mg/m2 as a 1-h infusion on day 1, folinic acid 100 mg/m2 intravenously on days 1–2, and 5-fluorouracil as a 400 mg/m2 bolus and then 600 mg/m2 continuous infusion over 22 h on days 1–2. Primary end-point was tumor response rate (confirmed complete and partial response). Results Twenty-six patients were enrolled. Overall response rate and disease control rate were 11.5% and 38.5%. The median progression free survival (PFS) was 52 days (95% CI:42–74), and the median overall survival was 117 days (95% CI: 94–154). no unexpected adverse events have been observed. A longer PFS and OS were observed in patients who had achieved PFS ≥ 3 months during prior ramucirumab treatment. Conclusions Our findings suggest a poor efficacy of the FOLFIRI regimen in metastatic gastric or gastroesophageal junction cancer patients whose disease progressed during a ramucirumab-based second line of treatment. However, FOLFIRI could be an option for patients who responded to prior ramucirumab.
KeywordsGastric cancer Irinotecan Ramucirumab Third line
Compliance with ethical standards
Conflict of interest
Roviello G declares that he has no conflict of interest. Petrioli R declares that he has no conflict of interest. Multari AG declares that he has no conflict of interest. Conca R declares that he has no conflict of interest. Paganini G declares that he has no conflict of interest. Chiariacò G declares that he has no conflict of interest. Aieta M declares that he has no conflict of interest.
Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 2.Marano L, Polom K, Patriti A, Roviello G, Falco G, Stracqualursi A, et al (2015) Surgical management of advanced gastric cancer: An evolving issue. Eur J Surg Oncol. Nov 14.Google Scholar
- 4.Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J (2014) REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. Jan 4 383(9911):31–39CrossRefGoogle Scholar
- 5.Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D et al (2014) Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15(11):1224–1235CrossRefGoogle Scholar
- 7.Kang EJ, Im SA, Oh DY, Han SW, Kim JS, Choi IS et al (2013) Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy afterfailure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival. Gastric Cancer 16(4):581–589CrossRefGoogle Scholar
- 12.Petrioli R, Roviello G, Zanotti L, Roviello F, Polom K, Bottini A, Marano L, Francini E, Marrelli D, Generali D (2016 Jun) Epirubicin-based compared with docetaxel-based chemotherapy for advanced gastric carcinoma: a systematic review and meta-analysis. Crit Rev Oncol Hematol 102:82–88CrossRefGoogle Scholar
- 13.Takahari D (2017 May) Second-line chemotherapy for patients with advanced gastric cancer. Gastric Cancer 20(3):395–406. https://doi.org/10.1007/s10120-017-0707-8 Epub 2017 Mar 4
- 14.De Vita F, Di Martino N, Fabozzi A, Laterza MM, Ventriglia J, Savastano B, Petrillo A, Gambardella V, Sforza V, Marano L, Auricchio A, Galizia G, Ciardiello F, Orditura M (2014 Oct 28) Clinical management of advanced gastric cancer: the role of new molecular drugs. World J Gastroenterol 20(40):14537–14558CrossRefGoogle Scholar
- 16.Yu Zheng MM, Xu-Qing Zhu BM, XiaoGang Ren MM (2017) Third-line chemotherapy in advanced gastric cancer A systematic review and meta-analysis. Medicine 96:24(e6884)Google Scholar
- 17.Erdem GU, Bozkaya Y, Ozdemir NY, Demirci NS, Yazici O, Zengin N (2018) 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as a third-line chemotherapy treatment in metastatic gastric cancer, after failure of fluoropyrimidine, platinum, anthracycline, and taxane. Bosn J Basic Med Sci 20;18(2):170–177Google Scholar
- 18.Roviello G, Ravelli A, Fiaschi AI et al (2016) Apatinib for the treatment of gastric cancer. Expert Review of Gastroenterology & Hepatology 10(8):887–892Google Scholar
- 21.Pavlakis N, Sjoquist KM, Tsobanis E, Martin AJ, Kang Y-K, Bang J, et al (2015) INTEGRATE: a randomized, phase II, double-blind, placebo-controlled study ofregorafenib in refractory advanced oesophagogastric cancer (AOGC): a studyby the Australasian Gastrointestinal Trials Group (AGITG)-final overall andsubgroup results. J. Clin. Oncol., Conference: 2015 Annual Meeting of theAmerican Society of Clinical Oncology, ASCO Chicago, IL United States. Conference Start: 20150529 Conference End: 20150602. ConferencePublication: (var.pagings). 33 (15 SUPPL. 1) (no pagination), 2015. Date ofPublication: 20 May 2015Google Scholar