Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 83, Issue 5, pp 867–874 | Cite as

A study of second-line irinotecan plus cisplatin vs. irinotecan alone in platinum-naïve patients with early relapse of gastric cancer refractory to adjuvant S-1 monotherapy: exploratory subgroup analysis of the randomized phase III TRICS trial

  • Kazuhiro NishikawaEmail author
  • Kenta Murotani
  • Kazumasa Fujitani
  • Hitoshi Inagaki
  • Yusuke Akamaru
  • Shinya Tokunaga
  • Masakazu Takagi
  • Shigeyuki Tamura
  • Naotoshi Sugimoto
  • Tadashi Shigematsu
  • Takaki Yoshikawa
  • Tohru Ishiguro
  • Masato Nakamura
  • Hiroko Hasegawa
  • Satoshi Morita
  • Yumi Miyashita
  • Akira Tsuburaya
  • Junichi Sakamoto
  • Toshimasa Tsujinaka
Original Article
  • 120 Downloads

Abstract

Backgrounds

Many patients with gastric cancer relapse during or early after adjuvant chemotherapy. The standard treatment for early relapse patients is a second-line chemotherapy (SLC) based on irinotecan, taxanes, or a platinum-based chemotherapy. The platinum-containing biweekly irinotecan plus cisplatin (IRI/CDDP) combination was assumed to be promising in several reports of clinical trials as SLC. TRICS trial, a randomized phase III study of IRI/CDDP vs. IRI in platinum-naïve gastric cancers refractory to S-1 monotherapy, revealed that both irinotecan-based chemotherapies were effective and well tolerated.

Methods

This study analyzed 108 patients in the TRICS trial who experienced early relapse. Patients receiving IRI/CDDP (IRI, 60 mg/m2; CDDP, 30 mg/m2, q2w) versus IRI (150 mg/m2, q2w) were compared regarding overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and safety.

Results

The OS was 14.0 (95% confidence interval [CI]: 11.0–21.2) and 14.0 (95% CI: 10.7–16.5) months for IRI/CDDP and IRI, respectively (hazard ratio [HR]: 0.782; 95% CI: 0.515–1.188, P = 0.249). No significant differences were observed for PFS (5.0 vs. 4.5 months, respectively; HR: 0.802; 95% CI: 0.543–1.185, P = 0.268) or ORR (19.6% [95% CI: 9.4–33.9%] vs. 23.3% [95% CI: 11.8–38.6%], respectively). The incidence of grade 3–4 anemia was higher for IRI/CDDP than for IRI (20% vs. 0%, respectively; P = 0.0006).

Conclusion

Our study showed no significant survival differences between IRI/CDDP and IRI in platinum-naïve patients who relapsed during or within 6 months after S-1 adjuvant therapy; therefore, IRI may be a good option in this population.

Clinical trial information

UMIN 000002571.

Keywords

Advanced gastric cancer Second-line chemotherapy Biweekly irinotecan plus cisplatin (IRI/CDDP) Early relapse S-1 adjuvant therapy 

Notes

Acknowledgements

We thank the investigators who enrolled patients in this trial. Furthermore, we deeply appreciate all patients who participated in the trial. This work was supported in part by the non-profit organization Epidemiological & Clinical Research Information Network (ECRIN).

Funding

This work was supported, in part, by the non-profit organization Epidemiological & Clinical Research Information Network (ECRIN). [No grant numbers apply].

Compliance with ethical standards

Conflict of interest

Kazuhiro Nishikawa has received honoraria from Chugai, Taiho, Yakult, Eli Lilly, Tsumura, and EA Pharma, and research funding from Yakult and Taiho, outside the submitted work. Takaki Yoshikawa has received lecture fees from Chugai, Taiho, Yakult, Eli Lilly and Ono, and for advisory work for Ono and MSD, outside the submitted work. Masato Nakamura has received honoraria from Chugai, Taiho, Merk, Takeda, Yakult, Eli Lilly, Bayer, Ono, and Otsuka Pharma, outside the submitted work. Satoshi Morita has received honoraria from Chugai and Taiho, outside the submitted work. Junichi Sakamoto has received consultant fee from Takeda, and Honoraria from Tsumura, Nihon Kayaku, and Chugai, outside the submitted work. All remaining authors have declared no conflicts of interest to declare.

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.

References

  1. 1.
    Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Furukawa H, Yamaguchi T et al (2007) Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 357:1810–1820CrossRefGoogle Scholar
  2. 2.
    Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T et al (2011) 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 29:4387–4393CrossRefGoogle Scholar
  3. 3.
    Ito S, Ohashi Y, Sasako M (2018) Survival after recurrence in patients with gastric cancer who receive S-1 adjuvant chemotherapy: exploratory analysis of the ACTS-GC trial. BMC Cancer 18(1):449. [Epub ahead of print]CrossRefGoogle Scholar
  4. 4.
    Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T et al (2013) Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol 31:4438–4444CrossRefGoogle Scholar
  5. 5.
    Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N et al (2014) Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer 50:1437–1445CrossRefGoogle Scholar
  6. 6.
    Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J et al (2014) Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol 15:78–86CrossRefGoogle Scholar
  7. 7.
    Kang HJ, Chang HM, Kim TW, Ryu MH, Sohn HJ, Yook JH et al (2005) Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy. Br J Cancer 92:246–251CrossRefGoogle Scholar
  8. 8.
    Park YH, Kim BS, Ryoo BY, Yang SH (2006) A phase II study of capecitabine plus 3-weekly oxaliplatin as first-line therapy for patients with advanced gastric cancer. Br J Cancer 94:959–963CrossRefGoogle Scholar
  9. 9.
    De Vita F, Orditura M, Matano E, Bianco R, Carlomagno C, Infusino S et al (2005) A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients. Br J Cancer 92:1644–1649CrossRefGoogle Scholar
  10. 10.
    Nishikawa K, Fujitani K, Inagaki H, Akamaru Y, Tokunaga S, Takagi M et al (2015) Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial. Eur J Cancer 51:808–816CrossRefGoogle Scholar
  11. 11.
    Sato A, Kurihara M, Matsukawa M, Shimada K, Yamazaki T, Nakamachi M et al (2001) Preliminary study of fortnightly irinotecan hydrochloride plus cisplatin therapy in patients with advanced gastric and colorectal cancer. Cancer Chemother Pharmacol 47:380–384CrossRefGoogle Scholar
  12. 12.
    Koizumi W, Kurihara M, Satoh A, Takiuchi H, Tanabe S, Shimada K et al (2005) Phase I/II study of bi-weekly irinotecan plus cisplatin in the treatment of advavced gastric cancer. Anticancer Res 25:1257–1262Google Scholar
  13. 13.
    Shitara K, Morita S, Fujitani K, Kadowaki S, Takiguchi N, Hirabayashi N et al (2012) Combination chemotherapy with S-1 plus cisplatin for gastric cancer that recurs after adjuvant chemotherapy with S-1: multi-institutional retrospective analysis. Gastric Cancer 15:245–251CrossRefGoogle Scholar
  14. 14.
    Nishikawa K, Tsuburaya A, Yoshikawa T, Takahashi M, Tanabe K, Yamaguchi K et al (2018) A phase II trial of capecitabine plus cisplatin (XP) for patients with advanced gastric cancer with early relapse after S-1 adjuvant therapy: XParTS-I trial. Gastric Cancer 21:811–818CrossRefGoogle Scholar
  15. 15.
    Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y 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 15:1224–1235CrossRefGoogle Scholar
  16. 16.
    Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH et al (2011) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379:315–321CrossRefGoogle Scholar
  17. 17.
    Fuse N, Bando H, Chin K, Ito S, Yoshikawa T, Tsuburaya A et al (2017) Adjuvant capecitabine plus oxaliplatin after D2 gastrectomy in Japanese patients with gastric cancer: a phase II study. Gastric Cancer 20:332–340CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Kazuhiro Nishikawa
    • 1
    Email author
  • Kenta Murotani
    • 2
  • Kazumasa Fujitani
    • 3
  • Hitoshi Inagaki
    • 4
  • Yusuke Akamaru
    • 5
  • Shinya Tokunaga
    • 6
  • Masakazu Takagi
    • 7
  • Shigeyuki Tamura
    • 8
  • Naotoshi Sugimoto
    • 9
  • Tadashi Shigematsu
    • 10
  • Takaki Yoshikawa
    • 11
  • Tohru Ishiguro
    • 12
  • Masato Nakamura
    • 13
  • Hiroko Hasegawa
    • 14
  • Satoshi Morita
    • 15
  • Yumi Miyashita
    • 16
  • Akira Tsuburaya
    • 17
  • Junichi Sakamoto
    • 18
  • Toshimasa Tsujinaka
    • 19
  1. 1.Department of SurgeryNational Hospital Organization Osaka National HospitalOsakaJapan
  2. 2.Biostatistics Center, Graduate School of MedicineKurume UniversityKurumeJapan
  3. 3.Department of SurgeryOsaka General Medical CenterOsakaJapan
  4. 4.Department of SurgeryInagaki ClinicOwariasahiJapan
  5. 5.Department of SurgeryIkeda Municipal HospitalIkedaJapan
  6. 6.Department of Medical OncologyOsaka City General HospitalOsakaJapan
  7. 7.Department of SurgeryShizuoka General HospitalShizuokaJapan
  8. 8.Department of SurgeryYao Municipal HospitalYaoJapan
  9. 9.Department of Medical OncologyOsaka International Cancer InstituteOsakaJapan
  10. 10.Department of GastroenterologySaiseikai Shiga Prefectural HospitalRittoJapan
  11. 11.Department of Gastric SurgeryThe National Hospital Organization National Cancer Center HospitalTokyoJapan
  12. 12.Department of Digestive Tract and General SurgerySaitama Medical CenterKawagoeJapan
  13. 13.Comprehensive Cancer CenterAizawa HospitalMatsumotoJapan
  14. 14.Department of GastroenterologyNational Hospital Organization Osaka National HospitalOsakaJapan
  15. 15.Department of Biomedical Statistics and BioinformaticsKyoto University Graduate School of MedicineKyotoJapan
  16. 16.Data Center, Epidemiological and Clinical Research Information NetworkKyotoJapan
  17. 17.Department of SurgeryOzawa HospitalOdawaraJapan
  18. 18.Tokai Central HospitalKakamigaharaJapan
  19. 19.Kaizuka City HospitalKaizukaJapan

Personalised recommendations