Efficacy of intraperitoneally administered paclitaxel for colorectal cancer with peritoneal metastases

Abstract

Purpose

Prognosis after peritoneal metastases in colorectal cancer is worse than that after lung or liver metastases. Previously, we demonstrated the safety of intraperitoneal (ip) administration of paclitaxel (PTX) combined with mFOLFOX6/CapeOX plus bevacizumab for colorectal cancer with peritoneal metastasis in a phase-I trial. Here, we evaluated the efficacy of this chemotherapy.

Methods

We enrolled six patients with histologically confirmed peritoneal metastases secondary to colorectal cancer. PTX was administered through a peritoneal access port, in combination with oxaliplatin-based systematic chemotherapy. Response rate, progression-free survival, 1-year survival rate, frequency of improvement in peritoneal cancer index (PCI), and cytology in peritoneal lavage were evaluated. This study was registered in the University Hospital Medical Information Network Clinical Trial Registry on July 1, 2016 (UNIN000022924).

Results

Three patients received the mFOLFOX6–bevacizumab regimen, whereas the other three received the CapeOX–bevacizumab regimen. The response rate was 25%. PCI score improved in 50% of the cases. Peritoneal lavage cytology that was positive in five patients before initiating the chemotherapy turned negative during chemotherapy in all patients. One-year survival rate was 100%, progression-free survival was 8.8 months (range, 6.8–12 months), and median survival time was 29.3 months.

Conclusion

The ip administration of PTX with systemic chemotherapy can potentially control peritoneal metastases in colorectal cancer.

This is a preview of subscription content, access via your institution.

Fig. 1

References

  1. 1.

    Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, Hasegawa K, Hotta K, Ishida H, Ishiguro M, Ishihara S, Kanemitsu Y, Kinugasa Y, Murofushi K, Nakajima TE, Oka S, Tanaka T, Taniguchi H, Tsuji A, Uehara K, Ueno H, Yamanaka T, Yamazaki K, Yoshida M, Yoshino T, Itabashi M, Sakamaki K, Sano K, Shimada Y, Tanaka S, Uetake H, Yamaguchi S, Yamaguchi N, Kobayashi H, Matsuda K, Kotake K, Sugihara K (2020) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol 25(1):1–42. https://doi.org/10.1007/s10147-019-01485-z

    Article  PubMed  Google Scholar 

  2. 2.

    Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, Pitot HC, Grothey A, Alberts SR, Sargent DJ (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(3):263–267. https://doi.org/10.1200/JCO.2011.37.1039

    Article  PubMed  Google Scholar 

  3. 3.

    Franko J, Shi Q, Meyers JP, Maughan TS, Adams RA, Seymour MT, Saltz L, Punt CJ, Koopman M, Tournigand C, Tebbutt NC, Diaz-Rubio E, Souglakos J, Falcone A, Chibaudel B, Heinemann V, Moen J, De Gramont A, Sargent DJ, Grothey A (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(12):1709–1719. https://doi.org/10.1016/S1470-2045(16)30500-9

    Article  PubMed  Google Scholar 

  4. 4.

    Hentzen J, Rovers KP, Kuipers H, van der Plas WY, Been LB, Hoogwater FJH, van Ginkel RJ, Hemmer PHJ, van Dam GM, de Hingh I, Kruijff S (2019) Impact of synchronous versus metachronous onset of colorectal peritoneal metastases on survival outcomes after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC): a multicenter, retrospective, observational study. Ann Surg Oncol 26(7):2210–2221. https://doi.org/10.1245/s10434-019-07294-y

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Gamboa AC, Zaidi MY, Lee RM, Speegle S, Switchenko JM, Lipscomb J, Cloyd JM, Ahmed A, Grotz T, Leiting J, Fournier K, Lee AJ, Dineen S, Powers BD, Lowy AM, Kotha NV, Clarke C, Gamblin TC, Patel SH, Lee TC, Lambert L, Hendrix RJ, Abbott DE, Vande Walle K, Lafaro K, Lee B, Johnston FM, Greer J, Russell MC, Staley CA, Maithel SK (2019) Optimal surveillance frequency after CRS/HIPEC for appendiceal and colorectal neoplasms: a multi-institutional analysis of the US HIPEC collaborative. Ann Surg Oncol. https://doi.org/10.1245/s10434-019-07526-1

  6. 6.

    Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, Lorimier G, Dube P, Glehen O (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(1):63–68. https://doi.org/10.1200/JCO.2009.23.9285

    Article  Google Scholar 

  7. 7.

    Baratti D, Kusamura S, Azmi N, Guaglio M, Montenovo M, Deraco M (2019) Colorectal peritoneal metastases treated by perioperative systemic chemotherapy and cytoreductive surgery with or without mitomycin C-based HIPEC: a comparative study using the peritoneal surface disease severity score (PSDSS). Ann Surg Oncol 27:98–106. https://doi.org/10.1245/s10434-019-07935-2

    Article  PubMed  Google Scholar 

  8. 8.

    Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J (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:Jco2018778613. https://doi.org/10.1200/jco.2018.77.8613

  9. 9.

    Takahara N, Isayama H, Nakai Y, Ishigami H, Satoi S, Mizuno S, Kogure H, Matsubara S, Yamamoto N, Yamaguchi H, Tada M, Kitayama J, Watanabe T, Koike K (2016) Intravenous and intraperitoneal paclitaxel with S-1 for treatment of refractory pancreatic cancer with malignant ascites. Investig New Drugs 34(5):636–642. https://doi.org/10.1007/s10637-016-0369-0

    CAS  Article  Google Scholar 

  10. 10.

    Murono K, Nagata H, Ishimaru K, Emoto S, Kaneko M, Hiyoshi M, Sasaki K, Otani K, Shuno Y, Nishikawa T, Tanaka T, Hata K, Kawai K, Nozawa H, Muro K, Ishihara S (2019) Safety of intraperitoneal paclitaxel combined with conventional chemotherapy for colorectal cancer with peritoneal carcinomatosis: a phase I trial. Cancer Chemother Pharmacol 83(1):145–150. https://doi.org/10.1007/s00280-018-3714-5

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Cassidy J (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(12):2013–2019. https://doi.org/10.1200/jco.2007.14.9930

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    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(18):3354–3358. https://doi.org/10.1002/cncr.28204

    CAS  Article  PubMed  Google Scholar 

Download references

Funding

This study is supported by Grants-in-Aid for Scientific Research (C: grant number 18K07194, C: grant number 19K09114, C: grant number 19K09115) from the Japan Society for the Promotion of Science.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Koji Murono.

Ethics declarations

Conflict of interest

K. Muro is on the advisory board meeting for Bristol-Myers Squibb and Nippon Kayaku Co, Ltd.

Ethical approval

This study was approved by the ethics committee of the University of Tokyo (P2015038-11X).

Statement of informed consent

Written informed consent was obtained from all patients.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1
figure2

Kaplan–Meier curves for a) progression-free survival and b) overall survival. The median progression-free survival was 8.8 months, and the median overall survival was 29.3 months. (PNG 280 kb)

ESM 2
figure3

(PNG 250 kb).

High resolution image (TIF 81 kb).

High resolution image (TIF 77 kb).

ESM 3

(DOCX 27 kb).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Murono, K., Nozawa, H., Nagata, H. et al. Efficacy of intraperitoneally administered paclitaxel for colorectal cancer with peritoneal metastases. Int J Colorectal Dis 35, 1945–1949 (2020). https://doi.org/10.1007/s00384-020-03649-0

Download citation

Keywords

  • Phase 1 trial
  • Intraperitoneal administration of paclitaxel
  • Colorectal cancer
  • Peritoneal metastases