Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
권호 표지
DOI QR코드

DOI QR Code

Intraperitoneal Paclitaxel Combined with S-1 Plus Oxaliplatin for Advanced Gastric Cancer with Peritoneal Metastasis: a Phase I Study

  • Kim, Dong-Wook (Department of Surgery, Dankook University College of Medicine) ;
  • Seo, Won Jun (Division of Foregut Surgery, Department of Surgery, Korea University College of Medicine) ;
  • Youn, Sang Il (Department of Surgery, Dankook University College of Medicine) ;
  • Jee, Ye Seob (Department of Surgery, Dankook University College of Medicine) ;
  • Jang, You-Jin (Division of Foregut Surgery, Department of Surgery, Korea University College of Medicine) ;
  • Kim, Jong-Han (Division of Foregut Surgery, Department of Surgery, Korea University College of Medicine)
  • Received : 2021.09.09
  • Accepted : 2021.12.17
  • Published : 2021.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: We designed a new regimen by combining intraperitoneal (IP) paclitaxel (PTX) with systemic S-1 plus oxaliplatin (SOX) for the treatment of advanced gastric cancer with peritoneal metastasis. This dose-escalation study aimed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of IP PTX administered weekly to patients. Materials and Methods: Eight cycles of IP PTX plus SOX regimen were administered to the patients. S-1 was administered orally twice daily at a dose of 80 mg/m2/day for 14 consecutive days, followed by 7 days of rest. Intravenous oxaliplatin was administered at a fixed dose of 100 mg/m2 on day 1, while IP PTX was administered on days 1 and 8. The initial dose of IP PTX was 40 mg/m2, and the dose escalation was set in units of 20 mg/m2 up to 80 mg/m2. Dose-limiting toxicities (DLTs) were defined as grade 3 non-hematologic toxicities, grade 4 leukopenia, grade 3 febrile neutropenia, and grade 3 thrombocytopenia. Results: Nine patients were included in the study. No DLTs were observed in any of the enrolled patients. Therefore, the MTD was not reached, and the RD of IP PTX was determined to be 80 mg/m2. Four patients (44%) showed a decreased peritoneal cancer index score on second-look laparoscopic examination. Conclusions: The present study determined the dose for further clinical trials of IP PTX to be 80 mg/m2, when combined with a systemic SOX regimen.

Keywords

Acknowledgement

We especially appreciate the enthusiasm and dedication of the PIPS-GC study group.

References

  1. Lee JH, Son SY, Lee CM, Ahn SH, Park DJ, Kim HH. Factors predicting peritoneal recurrence in advanced gastric cancer: implication for adjuvant intraperitoneal chemotherapy. Gastric Cancer 2014;17:529-536. https://doi.org/10.1007/s10120-013-0306-2
  2. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 2008;9:215-221. https://doi.org/10.1016/S1470-2045(08)70035-4
  3. Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol 2009;20:666-673. https://doi.org/10.1093/annonc/mdn717
  4. Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 2014;15:1224-1235. https://doi.org/10.1016/S1470-2045(14)70420-6
  5. Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687-697. https://doi.org/10.1016/S0140-6736(10)61121-X
  6. Kobayashi D, Kodera Y. Intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Gastric Cancer 2017;20:111-121. https://doi.org/10.1007/s10120-016-0662-9
  7. Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, 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: PHOENIXGC trial. J Clin Oncol 2018;36:1922-1929. https://doi.org/10.1200/JCO.2018.77.8613
  8. Chia DKA, So JBY. Recent advances in intra-peritoneal chemotherapy for gastric cancer. J Gastric Cancer 2020;20:115-126. https://doi.org/10.5230/jgc.2020.20.e15
  9. Takahashi N, Kanda M, Yoshikawa T, Takiguchi N, Fujitani K, Miyamoto K, et al. A randomized phase II multicenter trial to explore efficacy of weekly intraperitoneal in comparison with intravenous paclitaxel administered immediately after gastrectomy to the patients with high risk of peritoneal recurrence: final results of the INPACT trial. Gastric Cancer 2018;21:1014-1023. https://doi.org/10.1007/s10120-018-0817-y
  10. Imano M, Imamoto H, Itoh T, Satou T, Peng YF, Yasuda A, et al. Safety of intraperitoneal administration of paclitaxel after gastrectomy with en-bloc D2 lymph node dissection. J Surg Oncol 2012;105:43-47. https://doi.org/10.1002/jso.22065
  11. Esquivel J, Chua TC, Stojadinovic A, Melero JT, Levine EA, Gutman M, et al. Accuracy and clinical relevance of computed tomography scan interpretation of peritoneal cancer index in colorectal cancer peritoneal carcinomatosis: a multi-institutional study. J Surg Oncol 2010;102:565-570. https://doi.org/10.1002/jso.21601
  12. Kim DW, Jee YS, Kim CH, Kim JJ, Park S, Choi SI, et al. Multicenter retrospective analysis of intraperitoneal paclitaxel and systemic chemotherapy for advanced gastric cancer with peritoneal metastasis. J Gastric Cancer 2020;20:50-59. https://doi.org/10.5230/jgc.2020.20.e6
  13. Guideline Committee of the Korean Gastric Cancer Association (KGCA), Development Working Group & Review Panel. Korean Practice Guideline for Gastric Cancer 2018: an evidence-based, multi-disciplinary approach. J Gastric Cancer 2019;19:1-48. https://doi.org/10.5230/jgc.2019.19.e8
  14. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer 2021;24:1-21. https://doi.org/10.1007/s10120-020-01042-y
  15. Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res 1996;82:359-374. https://doi.org/10.1007/978-1-4613-1247-5_23
  16. Mohamed F, Sugarbaker PH. Intraperitoneal taxanes. Surg Oncol Clin N Am 2003;12:825-833. https://doi.org/10.1016/S1055-3207(03)00038-3
  17. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205-216. https://doi.org/10.1093/jnci/92.3.205
  18. Tan HL, Chia CS, Tan GH, Choo SP, Tai DW, Chua CW, et al. Gastric peritoneal carcinomatosis - a retrospective review. World J Gastrointest Oncol 2017;9:121-128. https://doi.org/10.4251/wjgo.v9.i3.121