Abstract/References

Short-term outcomes of neoadjuvant chemotherapy with capecitabine plus oxaliplatin for patients with locally advanced rectal cancer followed by total or tumor-specific mesorectal excision with or without lateral pelvic lymph node dissection

Wataru Sakamoto, Yasuyuki Kanke, Hisashi Onozawa, Hirokazu Okayama, Hisahito Endo, Shotaro Fujita, Motonobu Saito, Zenichiro Saze, Tomoyuki Momma, Koji Kono

Abstract

Background:The standard strategy in Japan for locally advanced rectal cancer is total mesorectal excision plus adjuvant chemotherapy. However, large tumors significantly restrict pelvic manipulation of the distal side of the tumor during surgery;therefore, from an oncological point of view, it is better to shrink the tumor as much as possible preoperatively to optimize the circumferential resection margin. In recent years, advances in systemic chemotherapy have significantly improved the tumor reduction effect, enabling such drug therapy prior to surgery for locally advanced rectal cancer. We herein retrospectively evaluated the clinical, short-term outcomes of patients treated by neoadjuvant chemotherapy (NAC) using capecitabin and oxaliplatin (CAPOX), focusing on overall safety as well as clinical and pathological staging responses to NAC.

Methods:We applied the preoperative chemotherapy protocol to T3-4, any N, M0 or M1a (with resectable metastases) (UICC 8th) Ra/Rb rectal cancers. The chemotherapy regimen consisted of four cycles of CAPOX. After NAC, curative intent surgery with total mesorectal excision/tumor-specific mesorectal excision with/without metastasectomy was performed. Adverse effects (AEs) and compliance with NAC, surgical complications, clinical and pathological staging were evaluated. All patients undergoing the protocol between January 2017 and June 2021 at Fukushima Medical University were enrolled.

Results:Twenty cases were enrolled. No severe AEs were observed either preoperatively or perioperatively. Preoperative assessment of NAC showed no cases of progressive disease (PD). Radical resection was achieved in all cases. Histological therapeutic grading after NAC revealed one grade 3, four grade 2, three grade 1b, eleven grade 1a and one grade 0 among all cases.

Conclusion:This study suggests that NAC for locally advanced rectal cancer is likely to be acceptable because there were no severe AEs pre- or perioperatively, radical resection was achieved in all cases, and there were no cases of PD.

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References

1. 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, 68(6):394-424, 2018.
2. Heald RJ. A new approach to rectal cancer. Br J Hosp Med, 22(3):277-281, 1979.
3. Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N, et al. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med, 336(14):980-987 1997.
4. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med, 351(17):1731-1740, 2004.
5. Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, et al. The TME trial after a median follow-up of 6 years:increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg, 246(5):693-701, 2007.
6. van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer:12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol, 12(6):575-582, 2011.
7. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med, 345(9):638-646, 2001.
8. Fernandez-Martos C, Garcia-Albeniz X, Pericay C, Maurel J, Aparicio J, Montagut C, et al. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery:long-term results of the Spanish GCR-3 phase II randomized trial†. Ann Oncol, 26(8):1722-1728, 2015.
9. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figure A, Wong R, et al. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol, 26(12):2006-2012, 2008.
10. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figure A, Wong R, et al. XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer:NO16966 updated results. Br J Cancer, 105(1):58-64, 2011.
11. Rectum. JSfCotCa. Japanese Classification of Colorectal Carcinoma, 2nd edition. Tokyo, Japan:Kanehara;2009.
12. Loos M, Quentmeier P, Schuster T, Nitsche U, Gertler R, Keerl A, et al. Effect of preoperative radio (chemo) therapy on long-term functional outcome in rectal cancer patients:a systematic review and meta-analysis. Ann Surg Oncol, 20(6):1816-1828, 2013.
13. Cercek A, Goodman KA, Hajj C, Weisberger E, Segal NH, Reidy-Lagunes DL, et al. Neoadjuvant chemotherapy first, followed by chemoradiation and then surgery, in the management of locally advanced rectal cancer. J Natl Compr Canc Netw, 12(4):513-519, 2014.
14. Goodman KA. Total neoadjuvant therapy for rectal cancer. Cancer Radiother, 22(5):459-465, 2018.
15. Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, et al. NCCN Guidelines Insights:Rectal Cancer, Version 6.2020. J Natl Compr Canc Netw, 18(7):806-815, 2020.
16. Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rödel C, Cervantes A, et al. Rectal cancer:ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 29 (Suppl 4):iv22-iv40, 2018.
17. Hata T, Takahashi H, Sakai D, Haraguchi N, Nishimura J, Kudo T, et al. Neoadjuvant CapeOx therapy followed by sphincter-preserving surgery for lower rectal cancer. Surg Today, 47(11):1372-1377, 2017.
18. Okuyama T, Sameshima S, Takeshita E, Yoshioka R, Yamagata Y, Ono Y, et al. Therapeutic effects of oxaliplatin-based neoadjuvant chemotherapy and chemoradiotherapy in patients with locally advanced rectal cancer:a single-center, retrospective cohort study. World J Surg Oncol, 16(1):105, 2018.
19. Miwa K, Oki E, Enomoto M, Ihara K, Ando K, Fujita F, et al. Randomized phase II study comparing the efficacy and safety of SOX versus mFOLFOX6 as neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer (KSCC1301). BMC Cancer, 21(1):23, 2021.
20. Matsumoto T, Hasegawa S, Zaima M, Inoue N, Sakai Y. Outcomes of Neoadjuvant Chemotherapy without Radiation for Rectal Cancer. Dig Surg, 32(4):275-283, 2015.
21. Hasegawa J, Nishimura J, Mizushima T, Miyake Y, Kim HM, Takemoto H, et al. Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer. Cancer Chemother Pharmacol, 73(5):1079-1087, 2014.
22. Schrag D, Weiser MR, Goodman KA, Gonen M, Hollywood E, Cercek A, et al. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer:a pilot trial. J Clin Oncol, 32(6):513-518, 2014.
23. Uehara K, Hiramatsu K, Maeda A, Sakamoto E, Inoue M, Kobayashi S, et al. Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer:N-SOG 03 Phase II trial. Jpn J Clin Oncol, 43(10):964-971, 2013.

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