Biweekly oxaliplatin plus S1 for Chinese elderly patients with advanced gastric or gastroesophageal junction cancer as the first-line therapy: a single-arm, phase 2 study

Zhichao Jiang, Aiping Zhou, Yongkun Sun, Wen Zhang, Zhichao Jiang, Aiping Zhou, Yongkun Sun, Wen Zhang

Abstract

Background: SOX (oxaliplatin and S1, every 3 weeks) is one of the most common first-line chemotherapy for advanced or metastatic G/GEJ (gastric or gastroesophageal junction) cancer in Asia, but it has noticeable hematological and neurological toxicity. In China, the majority of gastric cancer patients are middle-aged and elderly with poor tolerance to 3-weekly chemotherapy. Therefore, we aimed to assess efficacy and safety of biweekly SOX for Chinese advanced G/GEJ cancer patients aged ≥ 60 years as the first-line treatment in a single arm phase 2 study.

Methods: Oxaliplatin was administered intravenously on day 1 at 85 mg/m2. S-1 was given at 80, 100 or 120 mg/day, depending on the body surface area (< 1.25 m2, 1.25 to < 1.5 m2, or ≥ 1.5 m2), twice daily, on day 1-10, every 2 weeks. The primary endpoint was objective response rate (ORR), and the secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety.

Results: Between May 2016 and Sep 2018, 42 patients were enrolled. The median follow-up was 43.6 months. The ORR and DCR were 52.4% and 85.7%, respectively. The median PFS was 4.6 months (95%CI 2.486-6.714), and the median OS was 11.1 months (95%CI 8.001-14.199). The most common treatment-related adverse events (TRAEs) of any grade included thrombocytopenia (59.5%), neutropenia (57.1%), appetite loss (57.1%) and nausea (54.8%). Only two patients suffered from grade 3 TRAEs (4.8%), including neutropenia (1 patient, [2.4%]) and diarrhea (1 patient, [2.4%]). No ≥ grade 4 TRAEs occurred.

Conclusions: Biweekly SOX seemed to have favorable tolerance without compromising the efficacy as the first-line therapy in Chinese elderly patients aged ≥ 60 years with advanced G/GEJ cancer.

Trial registration: ClinicalTrials.gov ID: NCT04694404 (5/1/2021). This study was approved by the Ethical Committee of National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, (17-048/1303).

Keywords: Advanced G/GEJ adenocarcinoma; Objective response rate; Oxaliplatin; S1.

Conflict of interest statement

None of the authors declare any conflicts of interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Kaplan–Meier estimates of PFS of advanced G/GEJ cancer patients treated with biweekly SOX. PFS, progression free survival; G/GEJ cancer, gastric or gastroesophageal junction caner
Fig. 2
Fig. 2
Kaplan–Meier estimates of OS of advanced G/GEJ cancer patients treated with biweekly SOX. OS, overall survival; G/GEJ, gastric or gastroesophageal junction

References

    1. Chen WQ, Sun KX, Zheng RS, Zeng HM, Zhang SW, Xia CF, Yang ZX, Li H, Zou XN, He J. Cancer incidence and mortality in China 2014. Clin J Cancer Res. 2018;30(1):1–12. doi: 10.21147/j.issn.1000-9604.2018.01.01.
    1. Cao MM, Chen WQ. Epidemiology of cancer in China and the current status of prevention and control. Chin J Clin Oncol. 2019;46(3):145–149. doi: 10.3969/j.issn.1000-8179.2019.03.283.
    1. Zhou JC, Zheng RS, Zhuang GH, Zhang SW, Zeng HM, Chen R, Wang SM, Sun KX, Zou XN, Wei WQ, He J. Analysis on the trend of gastric cancer incidence and age change in cancer registration regions of China, 2000 to 2015. Pract Oncol J. 2020;34(1):1–5. doi: 10.11904/j.issn.1002-3070.2020.01.001.
    1. Law of the People's Republic of China on the Protection of the Rights and Interests of Elderly People. Chapter 1, Item 2.
    1. Xu RH, Wang AQ, Shen L, et al. 2019ASCO Abstract 4017.
    1. Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hamada C, Hyodo I. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naive patients with advanced gastric cancer. Ann Oncol. 2015;26(1):141–148. doi: 10.1093/annonc/mdu472.
    1. Kim GM, Jeung HC, Rha SY, Kim HS, Jung I, Nam BH, Lee KH, Chung HC. A randomized phase II trial of S-1-oxaliplatin versus capecitabine–oxaliplatin in advanced gastric cancer. Eur J Cancer. 2012;48(4):518–526. doi: 10.1016/j.ejca.2011.12.017.
    1. Lee KW, Chung IJ, Ryu MH, Park YI, Nam BH, Oh HS, Lee KH, Han HS, Seo BG, Jo JC, Lee HR, Kim JW, Park SR, Cho SH, Kang YK, SOPP study investigators Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial) Gastric Cancer. 2021;24(1):156–167. doi: 10.1007/s10120-020-01101-4.
    1. Lu YM, Liu ZC, Zhang J. S-1 plus oxaliplatin vs. S-1 as first-line treatment in patients with previously untreated advanced gastric cancer: a randomized phase II study. J Chemother. 2014;26(3):159–164. doi: 10.1179/1973947813Y.0000000128.
    1. Kashiwada T, Shinozaki K, Ueno S, Kawanaka H, Uno F, Okita Y, Fukahori M, Matsushita H, Emi Y, Shimokawa M, Makiyama A, Saeki H, Oki E, Maehara Y, Mori M, Baba E, Kyushu Study Group of Clinical Cancer (KSCC) Safety and efficacy of S-1 plus oxaliplatin 130 mg/m2 combination therapy in patients with previously untreated HER2-negative unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: a phase II trial (KSCC1501A) Int J Clin Oncol. 2021;26(2):345–354. doi: 10.1007/s10147-020-01803-w.
    1. Di Bisceglie, G. Di Maggio, F. Giuliani, V. Lorusso, S. Cinieri, G. Colucci, E. Maiello. Bi-weekly administration of capecitabine-oxaliplatin (XELOX-2) in first line treatment of advanced colorectal cancer (ACRC): preliminary results. EJC Supplements. 2008;6(14):120–120. 10.1016/j.ejcsup.2008.06.040.
    1. Grande C, Quintero G, Candamio S, Bouzas LP, Villanueva MJ, Campos B, Gallardo E, Alvarez E, Casal J, Mel JR, GrupoGallego de InvestigacionesOncológicas (GGIO) Biwekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer. J Geriatr Oncol. 2013;4(2):114–121. doi: 10.1016/j.jgo.2013.01.001.
    1. S Hall Peter, Swinson Daniel, A Cairns David, S Waters Justin, Petty Russell, Allmark Christine, Ruddock Sharon, Falk Stephen, Wadsley Jonathan, Rajarshi Roy, Tillett Tania, Nicoll Jonathan, Cummins Sebastian, Mano Joseph, Grumett Simon, Stokes Zuzana, Kamposioras Konstantinos-Velios, Chatterjee Anirban, Garcia Angel, Waddell Tom, Guptal Kamalnayan, Maisey Nick, Khan Mohammed, Dent Jo, Lord Simon, Crossley Ann, Katona Eszter, Marshall Helen, Grabsch Heike, Velikova Galina, Ow Pei Loo, Handforth Catherine, Howard Helen, Seymour Matthew, GO2 Trial Investigators Efficacy of reduced-intensity chemotherapy with oxaliplatin and capecitabine on quality of life and cancer control among older and frail patients with advanced gastroesophageal cancer: The GO2 phase 3 randomized clinical trial. JAMA Oncol. 2021;7(6):869–877. doi: 10.1001/jamaoncol.2021.0848.
    1. Shirasaka T. Development history and concept of an oral anticancer agent S-1 (TS-1): its clinical usefulness and future vistas. Jpn J Clin Oncol. 2009;39(1):2–15. doi: 10.1093/jjco/hyn127.
    1. Hamada C, Yamada Y, Azuma M, Nishikawa K, Gotoh M, Bando H, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hyodo I. Meta-analysis supporting noninferiority of oxaliplatin plus S-1 to cisplatin plus S-1 in first-line treatment of advanced gastric cancer (G-SOX study): indirect comparison with S-1 alone. Int J Clin Oncol. 2016;21(4):668–675. doi: 10.1007/s10147-015-0938-9.
    1. Montagnani M, Turrisi G, Marinozzi C, Aliberti C, Fiorentini G. Effectiveness and safety of oxaliplatin compared to cisplatin for advanced, unresectable gastric cancer: a systematic review and meta-analysis. Gastric Cancer. 2011;14(1):50–55. doi: 10.1007/s10120-011-0007-7.
    1. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. 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(3):215–221. doi: 10.1016/S1470-2045(08)70035-4.
    1. Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A. Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009;10(11):1063–1069. doi: 10.1016/S1470-2045(09)70259-1.
    1. Jin M, Lu H, Li J, Shen L, Chen Z, Shi Y, Song SZ, Qin S, Liu JR, Ouyang X. Randomized 3-armed phase III study of S-1 monotherapy versus S-1/CDDP (SP) versus 5-FU/CDDP (FP) in patients (pts) with advanced gastric cancer (AGC): SC-101 study. J Clin Oncol. 2008;26(15):4533–4533. doi: 10.1200/jco.2008.26.15_suppl.4533.
    1. Xiao C, Qian J, Zheng YL, Song F, Wang QF, Jiang HP, Mao CY, Xu N. A phase II study of biweekly oxaliplatin plus S-1 combination chemotherapy as a first-line treatment for patients with metastatic or advanced gastric cancer in China. Medicine. 2019;98(20):e15696. doi: 10.1097/MD.0000000000015696.
    1. Yang H, Xia L, Chen J, Zhang SQ, Martin V, Li QQ, Lin SQ, Chen JF, Calmette J, Lu M, Fu LY, Yang J, Pan ZZ, Yu K, He JJ, Morand E, Schlecht-Louf G, Krzysiek R, Zitvogel L, Kang BX, Zhang ZM, Leader A, Zhou PH, Lanfumey L, Shi MX, Kroemer G, Ma YT. Stress-glucocorticoid-TSC22D3 axis compromises therapy-induced antitumor immunity. Nat Med. 2019;25(9):1428–1441. doi: 10.1038/s41591-019-0566-4.
    1. Zitvogel L, Pietrocola F, Kroemer G. Nutrition, inflammation and cancer. Nat Immunol. 2017;18(8):843–850. doi: 10.1038/ni.3754.
    1. Zhi CY, Peng LQ, Zhang ZD, Ling N, Liu HX, Hua YW. Correlation between prognostic nutritional index and pathologic complete response after neoadjuvant chemotherapy in gastric cancer patients by propensity score matching. J China Med Univ. 2019;48(3):245–249. doi: 10.12007/j.issn.0258-4646.2019.03.011.
    1. Ye X, Yu JC, Kang WM, Ma ZQ, Meng QB, Cao ZJ, Tian SB. Correlation analysis between prognostic nutritional index and clinicopathological features and long-term prognosis of resectable gastric cancer. Chinese Journal of General Surgery. 2014;29(2):93–97. doi: 10.3760/cma.j.issn.1007-631X.2014.02.004.
    1. Zhang LX, Han WX, Wei ZJ, Xu Am. The evaluation of immune and nutrition-based prognostic index for gastric cancer. Chinese J Gen Surg. 2018;33(1):16–19. doi: 10.3760/cma.j.issn.1007-631X.2018.01.005.
    1. Hong SD, Zhou T, Fang WF, Xue C, Hu ZH, Qin T, Tang YN, Chen Y, Ma YX, Yang YP, Hou X, Huang Y, Zhao HY, Zhao YY, Zhang L. The prognostic nutritional index (PNI) predicts overall survival of small -cell lung cancer patients. Tumour Biol. 2015;36(5):3389–3397. doi: 10.1007/s13277-014-2973-y.
    1. Zhang D, Zhang L, Lu HW, Ji H, Lu L, Zhang Y, Li YM. Effects of enteral nutritional support on postoperative nutrition and chemotherapy tolerance of advanced gastric cancer. China J Mod Med. 2018;28(28):122–126. doi: 10.3969/j.issn.1005-8982.2018.28.022.

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