Adjuvant albumin-bound paclitaxel combined with S-1 vs. oxaliplatin combined with capecitabine after D2 gastrectomy in patients with stage III gastric adenocarcinoma: a phase III multicenter, open-label, randomized controlled clinical trial protocol
Xiangdong Cheng, Dan Wu, Nong Xu, Luchuan Chen, Zhilong Yan, Ping Chen, Lei Zhou, Jianfa Yu, Jiuwei Cui, Wei Li, Chang Wang, Wenming Feng, Yunhai Wei, Pengfei Yu, Yian Du, Jieer Ying, Zhiyuan Xu, Litao Yang, Yunli Zhang, Xiangdong Cheng, Dan Wu, Nong Xu, Luchuan Chen, Zhilong Yan, Ping Chen, Lei Zhou, Jianfa Yu, Jiuwei Cui, Wei Li, Chang Wang, Wenming Feng, Yunhai Wei, Pengfei Yu, Yian Du, Jieer Ying, Zhiyuan Xu, Litao Yang, Yunli Zhang
Abstract
Background: Surgery is the only treatment option for operable gastric cancer. The CLASSIC and ACTS-GC studies showed that the 5-year overall survival (OS) of patients with stage III gastric cancer undergoing D2 gastrectomy is still very low. Whether adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined chemotherapy is more effective than the XELOX standard adjuvant chemotherapy in patients with stage III gastric cancer has not been confirmed.
Methods: This is a multicenter, open-label, phase III clinical study. In this trial, 616 patients with locally advanced stage III gastric cancer that underwent curative D2 radical surgery and achieved R0 are planned to be included. Patients will be randomized 1:1 to nab-paclitaxel combined with S-1 (AS) vs. oxaliplatin combined with capecitabine (XELOX). XELOX group: Patients assigned to the XELOX group received eight 3-week cycles of oral capecitabine (1000 mg/m2) twice daily on days 1-14 of each cycle plus intravenous oxaliplatin 130 mg/m2 on day 1 of each cycle. AS group: AS group received eight 3-week cycles of oral S-1 (80-120 mg) (< 1.25 m2, 40 mg; 1.25 to < 1.5 m2, 50 mg; and > 1.5 m2, 60 mg) twice daily on days 1-14 plus intravenous nab-paclitaxel 120 mg/m2 on days 1 and 8 of each cycle. The primary endpoint was the 3-year disease-free survival (3-year-DFS) defined as the time from randomisation to the time of recurrence of the original gastric cancer, development of a new gastric cancer, or death from any cause. The secondary endpoints were the overall survival, (defined as the time from the date of randomisation to date of death from any cause) and safety (any adverse event).
Discussion: Compared with previous studies, this study includes nab-paclitaxel based on S-1 adjuvant chemotherapy, which is expected to achieve better efficacy and lower toxicity than the standard treatment. This study is the first clinical study to evaluate the safety and efficacy of nab-paclitaxel combined with S-1 in patients with stage III gastric cancer after D2 radical resection.
Trial registration: This clinical trial has been registered with ClinicalTrials.gov, registration number: NCT04135781 , on October 20th, 2019.
Keywords: Adjuvant chemotherapy; Albumin-bound paclitaxel; Gastric cancer; S-1; Surgery; Survival.
Conflict of interest statement
The authors declare that they have no competing interests.
Figures
References
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
- Zuo TZR, Zeng H, Zhang S, Chen W. Epidemiology of stomach cancer in China. Chin J Clin Oncol. 2017;44:52–58.
- Infection with Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum. 1994;61:177–240. .
- Plummer M, Franceschi S, Vignat J, Forman D, de Martel C. Global burden of gastric cancer attributable to helicobacter pylori. Int J Cancer. 2015;136(2):487–490. doi: 10.1002/ijc.28999.
- Isobe Y, Nashimoto A, Akazawa K, Oda I, Hayashi K, Miyashiro I, Katai H, Tsujitani S, Kodera Y, Seto Y, et al. Gastric cancer treatment in Japan: 2008 annual report of the JGCA nationwide registry. Gastric Cancer. 2011;14(4):301–316. doi: 10.1007/s10120-011-0085-6.
- Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357(18):1810–1820. doi: 10.1056/NEJMoa072252.
- Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(12):1389–1396. doi: 10.1016/S1470-2045(14)70473-5.
- Shitara K, Chin K, Yoshikawa T, Katai H, Terashima M, Ito S, Hirao M, Yoshida K, Oki E, Sasako M, et al. Phase II study of adjuvant chemotherapy of S-1 plus oxaliplatin for patients with stage III gastric cancer after D2 gastrectomy. Gastric Cancer. 2017;20(1):175–181. doi: 10.1007/s10120-015-0581-1.
- Takahari D, Hamaguchi T, Yoshimura K, Katai H, Ito S, Fuse N, Kinoshita T, Yasui H, Terashima M, Goto M, et al. Feasibility study of adjuvant chemotherapy with S-1 plus cisplatin for gastric cancer. Cancer Chemother Pharmacol. 2011;67(6):1423–1428. doi: 10.1007/s00280-010-1432-8.
- He MM, Wang F, Jin Y, Yuan SQ, Ren C, Luo HY, Wang ZQ, Qiu MZ, Wang ZX, Zeng ZL, et al. Phase II clinical trial of S-1 plus nanoparticle albumin-bound paclitaxel in untreated patients with metastatic gastric cancer. Cancer Sci. 2018;109(11):3575–3582. doi: 10.1111/cas.13813.
- Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29(33):4387–4393. doi: 10.1200/JCO.2011.36.5908.
- Professional Committee of Gastric Cancer CSoCO . Guidelines of Chinese Society of Clinical Oncology (CSCO) Gastric Cancer. 2019.
- Yoshikawa T, Terashima M, Mizusawa J, Nunobe S, Nishida Y, Yamada T, Kaji M, Fukushima N, Hato S, Choda Y, et al. Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104 [OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol. 2019;4(3):208–216. doi: 10.1016/S2468-1253(18)30383-2.
- Park SHZD, Han B, Ji JH, Kim TG, Oh SY, Hwang IG, Kim JH, Shin DB, Lim DH, Kim KM, An JY, Choi MG, Lee JH, Sohn TS, Bae JM, Kim S, Kim ST, Lee J, Kang WK. 2019 ASCO annual meeting. 2019. ARTIST 2 : Interim results of a phase III trial involving adjuvant chemotherapy and/or chemoradiotherapy after D2-gastrectomy in stage II/III gastric cancer (GC)
- Yoshida K, Kodera Y, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Watanabe T, et al. Addition of docetaxel to oral fluoropyrimidine improves efficacy in patients with stage III gastric cancer: interim analysis of JACCRO GC-07, a randomized controlled trial. J Clin Oncol. 2019;37(15):1296–1304. doi: 10.1200/JCO.18.01138.
Source: PubMed