Advertisement

Randomised phase II trial comparing four front-line doublets in Asian patients with metastatic gastric cancer

  • Author Footnotes
    1 These authors equally contribute to this work.
    Chan Kim
    Footnotes
    1 These authors equally contribute to this work.
    Affiliations
    Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
    Search for articles by this author
  • Author Footnotes
    1 These authors equally contribute to this work.
    Hong Jae Chon
    Footnotes
    1 These authors equally contribute to this work.
    Affiliations
    Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
    Search for articles by this author
  • Author Footnotes
    1 These authors equally contribute to this work.
    Joo Hoon Kim
    Footnotes
    1 These authors equally contribute to this work.
    Affiliations
    Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea
    Search for articles by this author
  • Minkyu Jung
    Affiliations
    Department of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, South Korea
    Search for articles by this author
  • Chung Mo Nam
    Affiliations
    Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
    Search for articles by this author
  • Hyo Song Kim
    Affiliations
    Department of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, South Korea
    Search for articles by this author
  • Beodeul Kang
    Affiliations
    Department of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, South Korea
    Search for articles by this author
  • Hyun Cheol Chung
    Affiliations
    Department of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, South Korea

    Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea

    Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea
    Search for articles by this author
  • Sun Young Rha
    Correspondence
    Corresponding author: Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-Ku, Seoul, 03722, South Korea. Fax: +82 2 362 5592.
    Affiliations
    Department of Medical Oncology, Yonsei Cancer Center, Yonsei University Health System, South Korea

    Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea

    Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea
    Search for articles by this author
  • Author Footnotes
    1 These authors equally contribute to this work.
Published:March 19, 2019DOI:https://doi.org/10.1016/j.ejca.2018.11.029

      Highlights

      • S-1 and cisplatin showed the most favourable results in progression-free survival (PFS).
      • Overall survival was similar among the four regimens.
      • All regimens were generally well-tolerated.
      • First-line platinum resulted in better PFS than first-line taxane.

      Abstract

      Introduction

      Consensus has not been reached regarding the standard regimen for front-line chemotherapy of recurrent/metastatic gastric cancer. In this randomised phase II study, we compared four doublet regimens: S-1 and cisplatin (SP); oxaliplatin and 5-FU (FOLFOX); docetaxel and 5-FU (DF) and paclitaxel and 5-FU (PF).

      Patients and methods

      Patients without prior history of chemotherapy for recurrent/metastatic gastric cancer were randomised evenly to each regimen. The primary end-point was progression-free survival (PFS). The secondary end-points were overall survival (OS), response rate (RR) and safety profile.

      Results

      A total of 179 Korean patients were enrolled from March 2010 to May 2015. The study was prematurely terminated because of slow accrual. At data cut-off, the median PFS was 8.4 months for SP, 5.8 months for FOLFOX, 5.7 months for DF and 4.2 months for PF (P = 0.023). The median OS was 14.7 months for SP, 11.3 months for FOLFOX, 11.7 months for DF and 10.8 months for PF (P = 0.143). RR was 18%, 23%, 16% and 32% for SP, FOLFOX, DF and PF, respectively. The platinum group displayed a longer PFS trend than the taxane group (7.2 versus 4.9 months, P = 0.058), but no significant difference in OS was found. Notably, 105 patients were exposed to all three drugs (platinum, taxane and fluoropyrimidine) throughout the treatment course, and OS was identical whether starting with platinum or taxane (13.3 versus 13.3 months, P = 0.997). All regimens were well tolerated.

      Conclusion

      SP showed the most favourable results in PFS, whereas a significant difference in OS was not observed among the four regimens.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ohtsu A.
        • Yoshida S.
        • Saijo N.
        Disparities in gastric cancer chemotherapy between the East and West.
        J Clin Oncol. 2006; 24: 2188-2196
        • Lordick F.
        • Lorenzen S.
        • Yamada Y.
        • Ilson D.
        Optimal chemotherapy for advanced gastric cancer: is there a global consensus?.
        Gastric Cancer. 2014; 17: 213-225
        • Bilici A.
        Treatment options in patients with metastatic gastric cancer: current status and future perspectives.
        World J Gastroenterol. 2014; 20: 3905-3915
        • Cunningham D.
        • Starling N.
        • Rao S.
        • Iveson T.
        • Nicolson M.
        • Coxon F.
        • et al.
        Capecitabine and oxaliplatin for advanced esophagogastric cancer.
        N Engl J Med. 2008; 358: 36-46
        • Yamada Y.
        • Higuchi K.
        • Nishikawa K.
        • Gotoh M.
        • Fuse N.
        • Sugimoto N.
        • et al.
        Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer.
        Ann Oncol. 2014; 26: 141-148
        • Van Cutsem E.
        • Moiseyenko V.M.
        • Tjulandin S.
        • Majlis A.
        • Constenla M.
        • Boni C.
        • et al.
        Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group.
        J Clin Oncol. 2006; 24: 4991-4997
        • Al-Batran S.-E.
        • Hartmann J.
        • Hofheinz R.
        • Homann N.
        • Rethwisch V.
        • Probst S.
        • et al.
        Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie.
        Ann Oncol. 2008; 19: 1882-1887
        • Al-Batran S.-E.
        • Homann N.
        • Schmalenberg H.
        • Kopp H.-G.
        • Haag G.M.
        • Luley K.B.
        • et al.
        Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial.
        J Clin Oncol. 2017; 35: 4004
        • Van Cutsem E.
        • Boni C.
        • Tabernero J.
        • Massuti B.
        • Middleton G.
        • Dane F.
        • et al.
        Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study.
        Ann Oncol. 2014; 26: 149-156
        • Yoshida K.
        • Ninomiya M.
        • Takakura N.
        • Hirabayashi N.
        • Takiyama W.
        • Sato Y.
        • et al.
        Phase II study of docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer.
        Clin Cancer Res. 2006; 12: 3402-3407
        • Park S.H.
        • Lee W.K.
        • Chung M.
        • Lee Y.
        • Han S.H.
        • Bang S.-M.
        • et al.
        Paclitaxel versus docetaxel for advanced gastric cancer: a randomized phase II trial in combination with infusional 5-fluorouracil.
        Anti Cancer Drugs. 2006; 17: 225-229
        • Chon H.J.
        • Rha S.Y.
        • Im C.K.
        • Kim C.
        • Hong M.H.
        • Kim H.R.
        • et al.
        Docetaxel versus paclitaxel combined with 5-FU and leucovorin in advanced gastric cancer: combined analysis of two phase II trials.
        Cancer Res Treat. 2009; 41: 196-204
        • Guo Z.
        • Wang X.
        • Lin R.
        • Chen L.
        • Fan N.
        • Chen Y.
        • et al.
        Paclitaxel-based regimens as first-line treatment in advanced gastric cancer.
        J Chemother. 2015; 27: 94-98
        • Shi C.
        • Chen Q.
        • Shen S.
        • Wu R.
        • Yang B.
        • Liu Q.
        • et al.
        Paclitaxel combined with oxaliplatin as first-line chemotherapy for locally advanced or metastatic gastric cancer.
        Expert Rev Anticancer Ther. 2015; 15: 595-601
        • Kim C.
        • Lee C.-K.
        • Chon H.J.
        • Kim J.H.
        • Park H.S.
        • Heo S.J.
        • et al.
        PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer.
        Oncotarget. 2017; 8: 113494-113501
        • Liu P.
        • Dahlberg S.
        • Crowley J.
        Selection designs for pilot studies based on survival.
        Biometrics. 1993; : 391-398
        • Mandrekar S.J.
        • Sargent D.J.
        Pick the winner designs in phase II cancer clinical trials.
        J Thoracic Oncol. 2006; 1: 5-6
        • Liang K.-Y.
        • Zeger S.L.
        Longitudinal data analysis using generalized linear models.
        Biometrika. 1986; 73: 13-22
        • Koizumi W.
        • Narahara H.
        • Hara T.
        • Takagane A.
        • Akiya T.
        • Takagi M.
        • et al.
        S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial.
        Lancet Oncol. 2008; 9: 215-221
        • Ryu M.-H.
        • Baba E.
        • Lee K.
        • Park Y.
        • Boku N.
        • Hyodo I.
        • et al.
        Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS).
        Ann Oncol. 2015; 26: 2097-2101
        • Chu Q.S.-C.
        • Hammond L.A.
        • Schwartz G.
        • Ochoa L.
        • Rha S.-Y.
        • Denis L.
        • et al.
        Phase I and pharmacokinetic study of the oral fluoropyrimidine S-1 on a once-daily-for-28-day schedule in patients with advanced malignancies.
        Clin Cancer Res. 2004; 10: 4913-4921
        • Ajani J.
        • Buyse M.
        • Lichinitser M.
        • Gorbunova V.
        • Bodoky G.
        • Douillard J.
        • et al.
        Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study.
        Eur J Cancer. 2013; 49: 3616-3624
        • Han S.
        • Oh D.
        • Im S.
        • Park S.
        • Lee K.
        • Song H.
        • et al.
        Phase II study and biomarker analysis of cetuximab combined with modified FOLFOX6 in advanced gastric cancer.
        Br J Cancer. 2009; 100: 298
        • Keam B.
        • Im S.-A.
        • Han S.-W.
        • Ham H.S.
        • Kim M.A.
        • Oh D.-Y.
        • et al.
        Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker.
        BMC Canc. 2008; 8: 148
        • Koizumi W.
        • Kim Y.H.
        • Fujii M.
        • Kim H.K.
        • Imamura H.
        • Lee K.H.
        • et al.
        Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START).
        J Cancer Res Clin Oncol. 2014; 140: 319-328
        • Kenmotsu H.
        • Tanigawara Y.
        Pharmacokinetics, dynamics and toxicity of docetaxel: why the Japanese dose differs from the Western dose.
        Cancer Sci. 2015; 106: 497-504
        • Ma J.
        • Shen H.
        • Kapesa L.
        • Zeng S.
        Lauren classification and individualized chemotherapy in gastric cancer.
        Oncol Lett. 2016; 11: 2959-2964
        • Lemoine N.
        • Adenis A.
        • Bouche O.
        • Duhamel A.
        • Heurgue A.
        • Leteurtre E.
        • et al.
        Signet ring cells and efficacy of first-line chemotherapy in advanced gastric or oesogastric junction adenocarcinoma.
        Anticancer Res. 2016; 36: 5543-5549
        • Chon H.J.
        • Hyung W.J.
        • Kim C.
        • Park S.
        • Kim J.-H.
        • Park C.H.
        • et al.
        Differential prognostic implications of gastric signet ring cell carcinoma: stage adjusted analysis from a single high-volume center in Asia.
        Ann Surg. 2017; 265: 946-953
        • Sun L.-B.
        • Zhao G.-J.
        • Ding D.-Y.
        • Song B.
        • Hou R.-Z.
        • Li Y.-C.
        Comparison between better and poorly differentiated locally advanced gastric cancer in preoperative chemotherapy: a retrospective, comparative study at a single tertiary care institute.
        World J Surg Oncol. 2014; 12: 280
        • Chon H.J.
        • Kim C.
        • Cho A.
        • Kim Y.M.
        • Jang S.J.
        • Kim B.O.
        • et al.
        The clinical implications of FDG-PET/CT differ according to histology in advanced gastric cancer.
        Gastric Cancer. 2018; : 1-10
        • Boku N.
        • Yamamoto S.
        • Fukuda H.
        • Shirao K.
        • Doi T.
        • Sawaki A.
        • et al.
        Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study.
        Lancet Oncol. 2009; 10: 1063-1069
        • Yamaguchi K.
        • Tada M.
        • Horikoshi N.
        • Otani T.
        • Takiuchi H.
        • Saitoh S.
        • et al.
        Phase II study of paclitaxel with 3-h infusion in patients with advanced gastric cancer.
        Gastric Cancer. 2002; 5: 90-95
        • Kawakami H.
        • Okamoto I.
        • Hayashi H.
        • Taguri M.
        • Morita S.
        • Nakagawa K.
        Postprogression survival for first-line chemotherapy in patients with advanced gastric cancer.
        Eur J Cancer. 2013; 49: 3003-3009
        • Wilke H.
        • Muro K.
        • Van Cutsem E.
        • Oh S.-C.
        • Bodoky G.
        • Shimada Y.
        • et al.
        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. 2014; 15: 1224-1235
        • Lordick F.
        • Janjigian Y.Y.
        Clinical impact of tumour biology in the management of gastroesophageal cancer.
        Nat Rev Clin Oncol. 2016; 13: 348-360