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Interim analysis of a phase II trial evaluating the safety and efficacy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer

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Abstract

Purpose

Adjuvant oxaliplatin plus oral capecitabine (XELOX) is recommended for patients with curatively resected colon cancer. However, its safety and tolerability in Asian patients is unclear; therefore, we evaluated the safety and efficacy of adjuvant XELOX in Japanese patients with curatively resected stage III colon cancer (MCSCO-1024) and present the interim safety data.

Methods

This prospective, multi-center, open-label, single-arm phase II study recruited patients with curatively resected stage III colon cancer. The protocol was a 120-min intravenous infusion of oxaliplatin (130 mg/m2) on day 1 and oral capecitabine (2000 mg/m2/day) in two divided doses for 14 days of a 3-week cycle, for a total of eight cycles (24 weeks). The primary endpoint was the 3-year disease-free survival, and secondary endpoints were the treatment completion rate, safety profile (rate and severity of adverse events), and correlation of adverse events, such as peripheral sensory neuropathy (PSN), with the administration period of oxaliplatin, etc.

Results

From November 2011 to August 2014 (34 months), 196 patients were enrolled. Safety was analyzed in 190 patients. The median total doses of capecitabine and oxaliplatin were 215,586.9 and 777.2 mg/m2, respectively, while the median relative dose intensities were 82.5 and 76.0%, respectively. The overall treatment completion rate was 73.7%. The most frequent treatment-related adverse event was PSN (88.4%), while the most frequent grade ≥3 treatment-related adverse events were neutropenia (12.6%), PSN (6.3%), diarrhea (4.2%), and thrombocytopenia (4.2%). There were no treatment-related deaths.

Conclusions

Adjuvant XELOX is tolerable for Japanese patients with Stage III colon cancer.

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References

  1. Kidani Y, Inagaki K, Iigo M, Hoshi A, Kuretani K (1978) Antitumor activity of 1, 2-diaminocyclohexane–platinum complexes against sarcoma-180 ascites form. J Med Chem 21:1315–1318. doi:10.1021/jm00210a029

    Article  CAS  PubMed  Google Scholar 

  2. Colvin H, Mizushima T, Eguchi H, Takiguchi S, Doki Y, Mori M (2017) Gastroenterological surgery in Japan: the past, the present and the future. Ann Gastroenterol Surg 1:5–10. doi:10.1002/ags3.12008

    Article  Google Scholar 

  3. NCCN clinical practice guideline: colon cancer. ver. 2 (2017). http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. Accessed 3 Apr 2017

  4. Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, Van de Velde CJ, Balmana J, Regula J (2012) ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 23:2479–2516. doi:10.1093/annonc/mds236

    Article  CAS  PubMed  Google Scholar 

  5. André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351. doi:10.1056/NEJMoa032709

    Article  PubMed  Google Scholar 

  6. Kuebler JP, Wieand HS, O’Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN (2007) Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 25:2198–2204. doi:10.1200/JCO.2006.08.2974

    Article  CAS  PubMed  Google Scholar 

  7. André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F (2009) Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27:3109–3116. doi:10.1200/JCO.2008.20.6771

    Article  PubMed  Google Scholar 

  8. Haller DG, Tabernero J, Maroun J, De Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ (2011) Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 29:1465–1471. doi:10.1200/JCO.2010.33.6297

    Article  CAS  PubMed  Google Scholar 

  9. Watanabe T, Itabashi M, Shimada Y, Tanaka S, Ito Y, Ajioka Y, Hamaguchi T, Hyodo I, Igarashi M, Ishida H (2012) Japanese society for cancer of the colon and rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol 17:1–29. doi:10.1007/s10147-011-0315-2

    Article  PubMed  Google Scholar 

  10. Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, De Braud F, Hill M, Sirzén F, Haller DG (2007) Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1864 patients. J Clin Oncol 25:102–109. doi:10.1200/JCO.2006.08.1075

    Article  CAS  PubMed  Google Scholar 

  11. Osawa H, Handa N, Minakata K (2014) Efficacy and safety of capecitabine and oxaliplatin (CapOX) as an adjuvant therapy in japanese for stage II/III colon cancer in a group at high risk of recurrence in retrospective study. Oncol Res 22:325–331. doi:10.3727/096504015X14410238486522

    Article  PubMed  Google Scholar 

  12. Chiu J, Tang V, Leung R, Wong H, Chu KW, Poon J, Epstein RJ, Yau T (2014) Efficacy and tolerability of adjuvant oral capecitabine plus intravenous oxaliplatin (XELOX) in Asian patients with colorectal cancer: 4-year analysis. Asian Pac J Cancer Prev 14:6585–6590. doi:10.7314/APJCP.2013.14.11.6585

    Article  PubMed  Google Scholar 

  13. Japanese Society for Cancer of the Colon and Rectum (2009) Japanese classification of colorectal carcinoma, Second English edn. Kanehara Shuppan, Tokyo

    Google Scholar 

  14. Sobin LH, Gospodarowicz MKWC (eds) (2009) Union against cancer (UICC) TNM classification of malignant tumours, 7th edn. Wiley, Oxford

    Google Scholar 

  15. Kotaka M, Yoshino T, Oba K, Shinozaki K, Touyama T, Manaka D, Matsui T, Ishigure K, Hasegawa J, Inoue K, Goto K, Sakamoto J, Saji S, Ohtsu A, Watanabe T (2015) Initial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy in patients with curatively resected stage II or III colon cancer (JFMC41-1001-C2: JOIN trial). Cancer Chemother Pharmacol 76:75–84. doi:10.1007/s00280-015-2757-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Allegra CJ, Yothers G, O’Connell MJ, Sharif S, Colangelo LH, Lopa SH, Petrelli NJ, Goldberg RM, Atkins JN, Seay TE (2009) Initial safety report of NSABP C-08: a randomized phase III study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage II or III colon cancer. J Clin Oncol 27:3385–3390. doi:10.1200/JCO.2009.21.9220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Doi T, Boku N, Kato K, Komatsu Y, Yamaguchi K, Muro K, Hamamoto Y, Sato A, Koizumi W, Mizunuma N, Takiuchi H (2010) Phase I/II study of capecitabine plus oxaliplatin (XELOX) plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer. Jpn J Clin Oncol 40:913–920. doi:10.1093/jjco/hyq069

    Article  PubMed  PubMed Central  Google Scholar 

  18. Uchima Y, Nishii T, Iseki Y, Ishii M, Hiramatsu S, Iwauchi T, Morimoto J, Kosaka K, Tei S, Takeuchi K (2014) Retrospective analysis of capecitabine and oxaliplatin (XELOX) plus bevacizumab as a first-line treatment for Japanese patients with metastatic colorectal cancer. Mol Clin Oncol 2:134–138. doi:10.3892/mco.2013.205

    Article  CAS  PubMed  Google Scholar 

  19. Haller DG, Cassidy J, Clarke SJ, Cunningham D, Van Cutsem E, Hoff PM, Rothenberg ML, Saltz LB, Schmoll HJ, Allegra C, Bertino JR, Douillard JY, Gustavsson BG, Milano G, O’Connell M, Rustum Y, Tabernero J, Gilberg F, Sirzén F, Twelves C (2008) Potential regional differences for the tolerability profiles of fluoropyrimidines. J Clin Oncol 26:2118–2123. doi:10.1200/JCO.2007.15.2090

    Article  CAS  PubMed  Google Scholar 

  20. Loprinzi CL, Qin R, Dakhil SR, Fehrenbacher L, Flynn KA, Atherton P, Seisler D, Qamar R, Lewis GC, Grothey A (2013) Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol 32:997–1005. doi:10.1200/JCO.2013.52.0536

    Article  PubMed  PubMed Central  Google Scholar 

  21. Oki E, Emi Y, Kojima H, Higashijima J, Kato T, Miyake Y, Kon M, Ogata Y, Takahashi K, Ishida H (2015) Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study. Int J Clin Oncol 20:767–775. doi:10.1007/s10147-015-0784-9

    Article  CAS  PubMed  Google Scholar 

  22. de Gramont AD, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947. doi:10.1200/JCO.2000.18.16.2938

    Article  PubMed  Google Scholar 

  23. André T, Iveson T, Labianca R, Meyerhardt JA, Souglakos I, Yoshino T, Paul J, Sobrero A, Taieb J, Shields AF (2013) The IDEA (international duration evaluation of adjuvant chemotherapy) collaboration: prospective combined analysis of phase III trials investigating duration of adjuvant therapy with the FOLFOX (FOLFOX4 or modified FOLFOX6) or XELOX (3 versus 6 months) re. Curr Colorectal Cancer Rep 9:261–269. doi:10.1007/s11888-013-0181-6

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ogata Y, Shimokawa M, Tanaka T, Emi Y, Oki E, Saeki H, Sadanaga N, Kusumoto T, Touyama T, Kimura M, Baba H, Akagi Y, Shirouzu K, Maehara Y (2016) A prospective study of XELOX plus bevacizumab as first-line therapy in Japanese patients with metastatic colorectal cancer (KSCC 0902). Int J Clin Oncol 21:335–343. doi:10.1007/s10147-015-0895-3

    Article  CAS  PubMed  Google Scholar 

  25. Emi Y, Kakeji Y, Oki E, Saeki H, Ando K, Kitazono M, Sakaguchi Y, Morita M, Samura H, Ogata Y, Akagi Y, Natsugoe S, Shirouzu K, Tokunaga S, Sirzen F, Maehara Y (2013) Initial report of KSCC0803: feasibility study of capecitabine as adjuvant chemotherapy for stage III colon cancer in Japanese patients. Int J Clin Oncol 18:254–259. doi:10.1007/s10147-011-0371-7

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Osaka General Medical Center, Sumiyoshi-ku, Osaka, Japan

    Katsuki Danno

  2. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Taishi Hata, Koki Tamai, Junichi Nishimura, Chu Matsuda, Tsunekazu Mizushima, Yuichiro Doki & Masaki Mori

  3. Department of Gastroenterological Surgery, NTT West Osaka Hospital, Tennouji-ku, Osaka, Japan

    Yujiro Fujie & Tadashi Ohnishi

  4. Department of Surgery, Yao Municipal Hospital, Yao, Osaka, Japan

    Yoshihito Ide

  5. Department of Surgery, Rinku General Medical Center, Izumisano, Osaka, Japan

    Ho Min Kim

  6. Department of Surgery, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan

    Shunji Morita

  7. Department of Surgery, Nishonomiya Municipal Central Hospital, Nishinomiya, Hyogo, Japan

    Shinichi Yoshioka & Riichiro Nezu

  8. Department of Frontier-Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan

    Toshihiro Kudo

  9. Department of Surgery, Osaka Police Hospital, Tennouji-ku, Osaka, Japan

    Hiroki Akamatsu

Authors
  1. Katsuki Danno
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  2. Taishi Hata
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  3. Koki Tamai
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  11. Junichi Nishimura
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  12. Chu Matsuda
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  14. Tsunekazu Mizushima
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  15. Riichiro Nezu
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  16. Yuichiro Doki
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  17. Masaki Mori
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Consortia

Multi-Center Clinical Study Group of Osaka

Colorectal Cancer Treatment Group (MCSGO)

Corresponding author

Correspondence to Taishi Hata.

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All authors declare that they have no conflict of interest.

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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.

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Informed consent was obtained from all individual participants included in the study.

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Danno, K., Hata, T., Tamai, K. et al. Interim analysis of a phase II trial evaluating the safety and efficacy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer. Cancer Chemother Pharmacol 80, 777–785 (2017). https://doi.org/10.1007/s00280-017-3419-1

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  • DOI: https://doi.org/10.1007/s00280-017-3419-1

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