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Cancer Chemotherapy and Pharmacology

, Volume 83, Issue 1, pp 145–150 | Cite as

Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial

  • Koji MuronoEmail author
  • Hiroshi Nagata
  • Kazuhiro Ishimaru
  • Shigenobu Emoto
  • Manabu Kaneko
  • Masaya Hiyoshi
  • Kazuhito Sasaki
  • Kensuke Otani
  • Yasutaka Shuno
  • Takeshi Nishikawa
  • Toshiaki Tanaka
  • Keisuke Hata
  • Kazushige Kawai
  • Hiroaki Nozawa
  • Kei Muro
  • Soichiro Ishihara
Original Article
  • 213 Downloads

Abstract

Purpose

Peritoneal carcinomatosis of colorectal cancer origin is associated with poor prognosis. With regard to ovarian, gastric, and pancreatic cancer, the safety and efficacy of intraperitoneal administration of paclitaxel (ip PTX) has been demonstrated. This drug can be administered easily and repeatedly through a catheter into the peritoneal cavity. In this phase I study, we evaluated the safety of ip PTX combined with 5-fluorouracil, folinic acid, oxaliplatin, and bevacizumab (mFOLFOX6-bevacizumab) or capecitabine, oxaliplatin, and bevacizumab (CapeOX-bevacizumab) for colorectal cancer with peritoneal metastasis.

Methods

Colorectal cancer patients with histologically confirmed peritoneal carcinomatosis were enrolled. After the implantation of a peritoneal access port, 20 mg/m2 of ip PTX was administered weekly, in combination with mFOLFOX6-bevacizumab or CapeOX-bevacizumab. Primary endpoint was the safety of the combination chemotherapy.

Results

Among the six patients enrolled, three received the mFOLFOX6-bevacizumab plus ip PTX regimen and three received the CapeOX-bevacizumab plus ip PTX regimen. Dose-limiting toxicity was not observed. Overall, grade 3 adverse events, such as leukopenia and neutropenia, were observed in two of three patients (66.7%) for each chemotherapeutic regimen, but no grade 4 adverse events were observed. Moreover, adverse events associated with the peritoneal access port, such as infection or occlusion of the catheter, were not observed.

Conclusions

The adverse events of mFOLFOX6-bevacizumab or CapeOX-bevacizumab in combination with ip PTX were considered similar to those described in previous studies of oxaliplatin-based treatment alone. 1 year after the start of chemotherapy, the efficacy of ip PTX will be evaluated as a secondary outcome.

Keywords

Phase I trial Intraperitoneal paclitaxel Colorectal cancer Peritoneal carcinomatosis 

Notes

Acknowledgements

This research is supported by Grants-in-Aid for Scientific Research (C: Grant number; 16K07143, C: Grant number; 16K07161, C: Grant number; 17K10620, C: Grant number; 17K10621, C: Grant number; 17K10623 and C: Grant number; 18K07194) from Japan Society for the promotion of Science. This research is supported by the Project for Cancer Research and Therapeutic Evolution (P-CREATE, grant number: 18 cm0106502h0003 from the Japan Agency for Medical Research and Development (AMED).

Compliance with ethical standards

Conflict of interest

K. Muro is on the advisory board meeting for Bristol-Myers Squibb and Nippon Kayaku Co, Ltd. All remaining authors have declared no conflicts of interest.

Ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee of the University of Tokyo (P2015038-11X) and with the 1964 Helsinki declaration and its later amendments. The study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) (UNIN000022924).

Informed consent

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

References

  1. 1.
    Jayne DG, Fook S, Loi C, Seow-Choen F (2002) Peritoneal carcinomatosis from colorectal cancer. Br J Surg 89:1545–1550CrossRefGoogle Scholar
  2. 2.
    Watanabe T, Muro K, Ajioka Y et al (2018) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23:1–34CrossRefGoogle Scholar
  3. 3.
    Franko J, Shi Q, Goldman CD et al (2012) Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol 30:263–267CrossRefGoogle Scholar
  4. 4.
    Franko J, Shi Q, Meyers JP et al (2016) Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol 17:1709–1719CrossRefGoogle Scholar
  5. 5.
    Murono K, Kawai K, Hata K et al (2018) Regimens of intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal cancer. Anticancer Res 38:15–22Google Scholar
  6. 6.
    Huang CQ, Min Y, Wang SY et al (2017) Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for peritoneal carcinomatosis from colorectal cancer: a systematic review and meta-analysis of current evidence. Oncotarget 8:55657–55683Google Scholar
  7. 7.
    Verwaal VJ, van Ruth S, de Bree E et al (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 21:3737–3743CrossRefGoogle Scholar
  8. 8.
    Elias D, Gilly F, Boutitie F et al (2010) Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol 28:63–68CrossRefGoogle Scholar
  9. 9.
    Quenet F, Goere D, Mehta SS et al (2011) Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis. Ann Surg 254:294–301CrossRefGoogle Scholar
  10. 10.
    Cashin PH, Mahteme H, Spang N et al (2016) Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: a randomised trial. Eur J Cancer 53:155–162CrossRefGoogle Scholar
  11. 11.
    Markman M, Rowinsky E, Hakes T et al (1992) Phase I trial of intraperitoneal taxol: a gynecologic oncology group study. J Clin Oncol 10:1485–1491CrossRefGoogle Scholar
  12. 12.
    Ishigami H, Kitayama J, Otani K et al (2009) Phase I pharmacokinetic study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer. Oncology 76:311–314CrossRefGoogle Scholar
  13. 13.
    Yamaguchi H, Kitayama J, Ishigami H, Emoto S, Yamashita H, Watanabe T (2013) A phase 2 trial of intravenous and intraperitoneal paclitaxel combined with S-1 for treatment of gastric cancer with macroscopic peritoneal metastasis. Cancer 119:3354–3358CrossRefGoogle Scholar
  14. 14.
    Takahara N, Isayama H, Nakai Y et al (2016) Intravenous and intraperitoneal paclitaxel with S-1 for treatment of refractory pancreatic cancer with malignant ascites. Investig New Drugs 34:636–642CrossRefGoogle Scholar
  15. 15.
    Satoi S, Fujii T, Yanagimoto H et al (2017) Multicenter phase II study of intravenous and intraperitoneal paclitaxel with S-1 for pancreatic ductal adenocarcinoma patients with peritoneal metastasis. Ann Surg 265:397–401CrossRefGoogle Scholar
  16. 16.
    Ishigami H, Fujiwara Y, Fukushima R et al (2018) Phase III Trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC Trial. J Clin Oncol 36(19):1922–1929CrossRefGoogle Scholar
  17. 17.
    Hribaschek A, Meyer F, Schneider-Stock R, Pross M, Ridwelski K, Lippert H (2007) Comparison of intraperitoneal with intravenous administration of taxol in experimental peritoneal carcinomatosis. Chemotherapy 53:410–417CrossRefGoogle Scholar
  18. 18.
    Jacquet P, Sugarbaker PH (1996) Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res 82:359–374CrossRefGoogle Scholar
  19. 19.
    Saltz LB, Clarke S, Diaz-Rubio E et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019CrossRefGoogle Scholar
  20. 20.
    Doi T, Boku N, Kato K et al (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 40:913–920CrossRefGoogle Scholar
  21. 21.
    Andre T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351CrossRefGoogle Scholar
  22. 22.
    Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544CrossRefGoogle Scholar
  23. 23.
    Cassidy J, Clarke S, Diaz-Rubio E et al (2011) XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cancer 105:58–64CrossRefGoogle Scholar
  24. 24.
    de Gramont A, Van Cutsem E, Schmoll HJ et al (2012) Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 13:1225–1233CrossRefGoogle Scholar
  25. 25.
    Yamada Y, Takahari D, Matsumoto H et al (2013) Leucovorin, fluorouracil, and oxaliplatin plus bevacizumab versus S-1 and oxaliplatin plus bevacizumab in patients with metastatic colorectal cancer (SOFT): an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 14:1278–1286CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Koji Murono
    • 1
    Email author
  • Hiroshi Nagata
    • 1
  • Kazuhiro Ishimaru
    • 1
  • Shigenobu Emoto
    • 1
  • Manabu Kaneko
    • 1
  • Masaya Hiyoshi
    • 1
  • Kazuhito Sasaki
    • 1
  • Kensuke Otani
    • 1
  • Yasutaka Shuno
    • 1
  • Takeshi Nishikawa
    • 1
  • Toshiaki Tanaka
    • 1
  • Keisuke Hata
    • 1
  • Kazushige Kawai
    • 1
  • Hiroaki Nozawa
    • 1
  • Kei Muro
    • 2
  • Soichiro Ishihara
    • 1
  1. 1.Division of Surgical Oncology, Department of Surgery, Faculty of MedicineThe University of TokyoTokyoJapan
  2. 2.Department of Clinical OncologyAichi Cancer Center HospitalNagoyaJapan

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