Skip to main content

Advertisement

Log in

Cytoreduction and Hyperthermic Intraperitoneal Paclitaxel and Cisplatin for Gastric Cancer with Peritoneal Metastasis

  • Peritoneal Surface Malignancy
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Peritoneal metastasis (PM) is the most common site of dissemination of gastric cancer (GC) and is associated with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for GC with PM remains controversial due to modest survival and significant morbidity.

Methods

We conducted a retrospective analysis of patients with GC and PM treated with CRS and HIPEC with cisplatin and paclitaxel for 90 min from June 2019 to December 2022.

Results

Twenty-two patients were included and received a median of 7 (interquartile range [IQR] 4–8) cycles of neoadjuvant systemic therapy. Seventeen patients (77%) underwent a single neoadjuvant laparoscopic HIPEC, and six (27%) patients received chemoradiation. The median Peritoneal Carcinomatosis Index at the time of CRS was 1 (IQR 0–4), and 21 patients (95%) underwent complete cytoreduction (CC-0). An R0 resection was achieved in 20 (91%) patients, and the median length of stay was 5.5 (IQR 4–7.5) days. There were six (27%) 90-day major complications (Clavien–Dindo grade ≥ 3), one (4%) Common Terminology Classification for Adverse Events (CTCAE) grade 4 cytopenia, and one (4%) acute kidney injury. The rate of anastomotic leak (all grades) was 14%, the 30-day readmission rate was 18%, and the 90-day mortality rate was 0%. At a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 1-, 2-, and 3-year PFS rates were 65%, 56%, and 40%, respectively, and the 1-, 2-, and 3-year OS rates were 96%, 78%, and 55%, respectively.

Conclusions

CRS and HIPEC with paclitaxel and cisplatin is well tolerated and is associated with favorable oncologic and perioperative outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ikoma N, Blum M, Chiang YJ, et al. Yield of staging laparoscopy and lavage cytology for radiologically occult peritoneal carcinomatosis of gastric cancer. Ann Surg Oncol. 2016;23(13):4332–7. https://doi.org/10.1245/s10434-016-5409-7.

    Article  PubMed  Google Scholar 

  2. Ikoma N, Chen HC, Wang X, et al. Patterns of initial recurrence in gastric adenocarcinoma in the era of preoperative therapy. Ann Surg Oncol. 2017;24(9):2679–87. https://doi.org/10.1245/s10434-017-5838-y.

    Article  PubMed  Google Scholar 

  3. Thomassen I, van Gestel YR, van Ramshorst B, et al. Peritoneal carcinomatosis of gastric origin: a population-based study on incidence, survival and risk factors. Int J Cancer. 2014;134(3):622–8. https://doi.org/10.1002/ijc.28373.

    Article  CAS  PubMed  Google Scholar 

  4. Sirody J, Kaji AH, Hari DM, Chen KT. Patterns of gastric cancer metastasis in the United States. Am J Surg. 2022;224(1 Pt B):445–8. https://doi.org/10.1016/j.amjsurg.2022.01.024.

    Article  PubMed  Google Scholar 

  5. Kang YK, Chen LT, Ryu MH, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(2):234–47. https://doi.org/10.1016/s1470-2045(21)00692-6.

    Article  CAS  PubMed  Google Scholar 

  6. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27–40. https://doi.org/10.1016/s0140-6736(21)00797-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Takahashi Y, Sunakawa Y, Inoue E, et al. Real-world effectiveness of nivolumab in advanced gastric cancer: the DELIVER trial (JACCRO GC-08). Gastric Cancer. 2022;25(1):235–44. https://doi.org/10.1007/s10120-021-01237-x.

    Article  CAS  PubMed  Google Scholar 

  8. Rudloff U, Langan RC, Mullinax JE, et al. Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial. J Surg Oncol. 2014;110(3):275–84. https://doi.org/10.1002/jso.23633.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yang XJ, Huang CQ, Suo T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18(6):1575–81. https://doi.org/10.1245/s10434-011-1631-5.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Green BL, Blumenthaler AN, Gamble LA, et al. Cytoreduction and HIPEC for gastric carcinomatosis: multi-institutional analysis of two phase II clinical trials. Ann Surg Oncol. 2023;30(3):1852–60. https://doi.org/10.1245/s10434-022-12761-0.

    Article  PubMed  Google Scholar 

  11. Ishigami H, Fujiwara Y, Fukushima R, et al. 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. 2018;36(19):1922–9. https://doi.org/10.1200/jco.2018.77.8613.

    Article  CAS  PubMed  Google Scholar 

  12. Paredes AZ, Guzman-Pruneda FA, Abdel-Misih S, et al. Perioperative morbidity of gastrectomy during CRS-HIPEC: an ACS-NSQIP analysis. J Surg Res. 2019;241:31–9. https://doi.org/10.1016/j.jss.2019.03.036.

    Article  PubMed  Google Scholar 

  13. Blum Murphy M, Ikoma N, Wang X, et al. Phase I trial of hyperthermic intraperitoneal chemoperfusion (HIPEC) with cisplatin, mitomycin, and paclitaxel in patients with gastric adenocarcinoma and associated carcinomatosis or positive cytology. Ann Surg Oncol. 2020;27(8):2806–11. https://doi.org/10.1245/s10434-020-08226-x.

    Article  PubMed  Google Scholar 

  14. Cullinan SA, Moertel CG, Fleming TR, et al. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985;253(14):2061–7.

    Article  CAS  PubMed  Google Scholar 

  15. Hartmann JT, Quietzsch D, Daikeler T, et al. Mitomycin C continuous infusion as salvage chemotherapy in pretreated patients with advanced gastric cancer. Anticancer Drugs. 1999;10(8):729–33. https://doi.org/10.1097/00001813-199909000-00006.

    Article  CAS  PubMed  Google Scholar 

  16. Kim NK, Park YS, Heo DS, et al. A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer. 1993;71(12):3813–8. https://doi.org/10.1002/1097-0142(19930615)71:12%3c3813::aid-cncr2820711205%3e3.0.co;2-5.

    Article  CAS  PubMed  Google Scholar 

  17. Tebbutt NC, Norman A, Cunningham D, et al. A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer. Ann Oncol. 2002;13(10):1568–75. https://doi.org/10.1093/annonc/mdf273.

    Article  CAS  PubMed  Google Scholar 

  18. Saikawa Y, Kubota T, Kuo TH, et al. Synergistic antitumor activity of mitomycin C and cisplatin against gastric cancer cells in vitro. J Surg Oncol. 1993;54(2):98–102. https://doi.org/10.1002/jso.2930540209.

    Article  CAS  PubMed  Google Scholar 

  19. Saikawa Y, Kubota T, Kuo TH, et al. Synergistic antitumor activity of combination chemotherapy with mitomycin C and cisplatin against human gastric cancer xenografts in nude mice. J Surg Oncol. 1994;56(4):242–5. https://doi.org/10.1002/jso.2930560408.

    Article  CAS  PubMed  Google Scholar 

  20. Kano Y, Akutsu M, Tsunoda S, Suzuki K, Yazawa Y. In vitro schedule-dependent interaction between paclitaxel and cisplatin in human carcinoma cell lines. Cancer Chemother Pharmacol. 1996;37(6):525–30. https://doi.org/10.1007/s002800050424.

    Article  CAS  PubMed  Google Scholar 

  21. Tanaka R, Ariyama H, Qin B, et al. In vitro schedule-dependent interaction between paclitaxel and oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol. 2005;55(6):595–601. https://doi.org/10.1007/s00280-004-0966-z.

    Article  CAS  PubMed  Google Scholar 

  22. de Bree E, Rosing H, Filis D, et al. Cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy with paclitaxel: a clinical and pharmacokinetic study. Ann Surg Oncol. 2008;15(4):1183–92. https://doi.org/10.1245/s10434-007-9792-y.

    Article  PubMed  Google Scholar 

  23. Leunig M, Goetz AE, Dellian M, et al. Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response. Cancer Res. 1992;52(2):487–90.

    CAS  PubMed  Google Scholar 

  24. Hettinga JV, Konings AW, Kampinga HH. Reduction of cellular cisplatin resistance by hyperthermia–a review. Int J Hyperthermia Sep-Oct. 1997;13(5):439–57. https://doi.org/10.3109/02656739709023545.

    Article  CAS  Google Scholar 

  25. Hettinga JV, Lemstra W, Meijer C, et al. Mechanism of hyperthermic potentiation of cisplatin action in cisplatin-sensitive and -resistant tumour cells. Br J Cancer. 1997;75(12):1735–43. https://doi.org/10.1038/bjc.1997.297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hettinga JVE. Reduction of cisplatin resistance by hyperthermia [thesis]. University of Groningen; 1996.

  27. Ansaloni L, Coccolini F, Morosi L, et al. Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer. Br J Cancer. 2015;112(2):306–12. https://doi.org/10.1038/bjc.2014.602.

    Article  CAS  PubMed  Google Scholar 

  28. Fugazzola P, Coccolini F, Montori G, et al. Overall and disease-free survival in patients treated with CRS + HIPEC with cisplatin and paclitaxel for gastric cancer with peritoneal carcinomatosis. J Gastrointest Oncol. 2017;8(3):572–82. https://doi.org/10.21037/jgo.2017.03.11.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Schwartz LH, Litière S, de Vries E, et al. RECIST 1.1-Update and clarification: from the RECIST committee. Eur J Cancer. 2016;62:132–7. https://doi.org/10.1016/j.ejca.2016.03.081.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Jh O, Lodge MA, Wahl RL. Practical PERCIST: a simplified guide to PET response criteria in solid tumors 1.0. Radiology. 2016;280(2):576–84. https://doi.org/10.1148/radiol.2016142043.

    Article  Google Scholar 

  31. Venkataraman R, Kellum JA. Defining acute renal failure: the RIFLE criteria. J Intensive Care Med. 2007;22(4):187–93. https://doi.org/10.1177/0885066607299510.

    Article  PubMed  Google Scholar 

  32. Ryan R, Gibbons D, Hyland JM, et al. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology. 2005;47(2):141–6. https://doi.org/10.1111/j.1365-2559.2005.02176.x.

    Article  CAS  PubMed  Google Scholar 

  33. The Chicago Consensus on Peritoneal Surface Malignancies: Management of Gastric Metastases. Ann Surg Oncol. 2020;27(6):1768-1773. https://doi.org/10.1245/s10434-020-08320-0.

  34. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20(2):167–92. https://doi.org/10.6004/jnccn.2022.0008.

    Article  CAS  PubMed  Google Scholar 

  35. Bonnot PE, Piessen G, Kepenekian V, et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastases (CYTO-CHIP study): a propensity score analysis. J Clin Oncol. 2019;37(23):2028–40. https://doi.org/10.1200/jco.18.01688.

    Article  CAS  PubMed  Google Scholar 

  36. Seretis C, Youssef H. Quality of life after cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies: a systematic review. Eur J Surg Oncol. 2014;40(12):1605–13. https://doi.org/10.1016/j.ejso.2014.08.477.

    Article  CAS  PubMed  Google Scholar 

  37. Papenfuss WA, Kukar M, Oxenberg J, et al. Morbidity and mortality associated with gastrectomy for gastric cancer. Ann Surg Oncol. 2014;21(9):3008–14. https://doi.org/10.1245/s10434-014-3664-z.

    Article  PubMed  Google Scholar 

  38. Ikoma N, Agnes A, Chen HC, et al. Linitis plastica: a distinct type of gastric cancer. J Gastrointest Surg. 2020;24(5):1018–25. https://doi.org/10.1007/s11605-019-04422-7.

    Article  PubMed  Google Scholar 

  39. Khan N, Donohoe CL, Phillips AW, Griffin SM, Reynolds JV. Signet ring gastric and esophageal adenocarcinomas: characteristics and prognostic implications. Dis Esophagus. 2020. https://doi.org/10.1093/dote/doaa016.

    Article  PubMed  Google Scholar 

  40. Pereira MA, Ramos M, Dias AR, et al. Lymph node regression after neoadjuvant chemotherapy: a predictor of survival in gastric cancer. J Surg Oncol. 2020;121(5):795–803. https://doi.org/10.1002/jso.25785.

    Article  CAS  PubMed  Google Scholar 

  41. Su P, Zhang Y, Yu T, et al. Comparison of the predictive value of pathological response at primary tumor and lymph node status after neoadjuvant chemotherapy in locally advanced gastric cancer. Clin Transl Oncol. 2023;25(8):2462–71. https://doi.org/10.1007/s12094-023-03130-8.

    Article  CAS  PubMed  Google Scholar 

  42. Badgwell B, Ikoma N, Murphy MB, et al. A phase II trial of cytoreduction, gastrectomy, and hyperthermic intraperitoneal perfusion with chemotherapy for patients with gastric cancer and carcinomatosis or positive cytology. Ann Surg Oncol. 2021;28(1):258–64. https://doi.org/10.1245/s10434-020-08739-5.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Travis E. Grotz MD.

Ethics declarations

Disclosures

EeeLN Buckarma, Cornelius Thiels, Zhaohui Jin, and Travis E. Grotz have no conflicts of interest to declare.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Buckarma, E., Thiels, C.A., Jin, Z. et al. Cytoreduction and Hyperthermic Intraperitoneal Paclitaxel and Cisplatin for Gastric Cancer with Peritoneal Metastasis. Ann Surg Oncol 31, 622–629 (2024). https://doi.org/10.1245/s10434-023-14379-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-023-14379-2

Keywords

Navigation