Neoadjuvant treatment of gastric cancer with peritoneal dissemination

https://doi.org/10.1016/j.ejso.2006.03.007Get rights and content

Abstract

Aims

To report our experience of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for patients having a complete resection of the primary gastric cancer and peritoneal carcinomatosis (PC).

Patients and methods

Patients with advanced peritoneal dissemination of primary gastric cancer had the placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5-fluorouracil were infused via a peripheral vein. A minimum of two cycles and up to six cycles of NIPS were used prior to cancer resection. At surgery a complete removal of the primary gastric cancer and the peritoneal implants by peritonectomy was attempted.

Results

Sixty-one patients were enrolled in the study. Thirty-nine had positive intraperitoneal cytology which reverted to negative cytology after treatment in 22. Thirty-eight showed a partial response. Thirty patients came to resection and 14 patients could be made disease-free. Median survival time of all patients was 14.4 months. Patients who received a complete resection had a median survival time of 20.4 months. Grade III/IV toxicities were not found after two courses of NIPS, but did develop in seven patients after more than three courses of NIPS.

Conclusion

NIPS can downstage large volume peritoneal dissemination of gastric cancer. When combined with gastrectomy including peritonectomy a complete surgical resection was possible in one-quarter of the patients and resulted in a prolonged survival. This combined intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of consideration for phase III clinical investigations.

Introduction

In all studies that address the treatment of carcinomatosis for gastric cancer, complete cytoreduction is a requirement for prolonged survival in the management of this condition.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 For gastric cancer the proportion of patients who receive a complete cytoreduction is small; even in selected patients less than one-third of patients have resection of all visible cancer.7, 8 Neoadjuvant chemotherapy has been proposed as a treatment modality that would increase the proportion of gastric cancer patients with peritoneal seeding who could receive a complete clearing of the cancer.12, 13 Unfortunately, systemic neoadjuvant chemotherapy has never significantly downstaged peritoneal seeding and the presence of carcinomatosis is considered by many a contraindication to the neoadjuvant treatment strategy.

We report a new neoadjuvant treatment modality for gastric cancer with peritoneal seeding; it combines intraperitoneal with systemic chemotherapy in an attempt to eradicate disease on visceral peritoneal surfaces and thereby increase the proportion of patients who may receive complete cytoreduction. It is an attempt to eradicate cancer nodules by multimodality chemotherapy that would enter the cancer nodule from the systemic circulation but also diffuse into the nodule from a chemotherapy solution in the peritoneal cavity. A prospective phase II study was initiated to demonstrate the efficacy of this treatment in the palliation of patients with gastric cancer and carcinomatosis and further explore its toxicities.

Section snippets

Patients

Patients were enrolled between April, 2001 and December, 2003. PC was diagnosed by biopsy using laparotomy, laparoscopy, or by the cytologic examination of ascites. The eligibility criteria included: (1) histologically or cytologically proven PC from gastric adenocarcinoma; (2) absence of hematogenous metastasis and remote lymph node metastasis; (3) age 65 years or younger; (4) Eastern Clinical Oncology Group scale of performance status 2 or less; (5) adequate bone marrow, liver, cardiac, and

Results

Clinical characteristics of the 61 patients are listed in Table 1. The average age was 45.6 years. All 61 patients had P3 dissemination. Ascites was present in 33 patients. Twenty-eight patients had primary gastric cancer and the remaining 33 patients had recurrent PC.

Prior to NIPS chemotherapy, peritoneal fluid cytology was positive in 39 patients and reverted to negative cytology after treatment in 22. In 33 patients with ascites, all peritoneal fluid disappeared in 12 patients after NIPS

Chemotherapy for PC

In the treatment of cancer arising from gastrointestinal tract, PC has long been considered as a fatal disease, and most surgeons have considered PC as a non-surgical condition. Recently, some investigators have reported limited success with new treatment strategies which include intraperitoneal chemo-hyperthermia, early postoperative intraperitoneal chemotherapy and peritonectomy.3, 4, 5, 6, 7, 8, 9 These studies suggest that intraperitoneal chemotherapy can deliver a high dose intensity into

References (31)

  • K. Hirose et al.

    Efficacy of continuous hyperthermic peritoneal perfusion for the prophylaxis and treatment of peritoneal metastasis of advanced gastric cancer

    Oncology

    (1999)
  • O. Glehen et al.

    Surgery combined with peritonectomy procedures and intraperitoneal chemohyperthermia in abdominal cancers with peritoneal carcinomatosis: A phase II study

    J Clin Oncol

    (2003)
  • P.H. Sugarbaker

    Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy

    Ann Surg Oncol

    (1999)
  • Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Patient registry of combined treatment for colorectal carcinomatosis. J...
  • H. Wilke et al.

    Preoperative chemotherapy in locally advanced and nonresectable gastric cancer: a phase II study with etoposide, doxorubicin, and cisplatin

    J Clin Oncol

    (1989)
  • Cited by (125)

    • Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable peritoneal metastasis from gastric cancer

      2021, European Journal of Surgical Oncology
      Citation Excerpt :

      Finally, in our study, all patients had systemic chemotherapy alternating with PIPAC. They were restarted on systemic chemotherapy after PIPAC within a median delay of 14 [4–28] days. Our treatment schedule proposing alternating systemic chemotherapy and PIPAC procedure as previously described by our group [31–34] seemed feasible and did not delayed the systemic treatment scheduled.

    • The role of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in ovarian cancer

      2024, Ovarian Cancer: The "Gynaecological Challenge? From Diagnostic Work-Up to Cytoreduction and Chemotherapy
    • Japanese practice of comprehensive treatment for peritoneal metastasis of gastric cancer

      2023, Chinese Journal of Gastrointestinal Surgery / Zhonghua Wei Chang Wai Ke Za Zhi
    View all citing articles on Scopus
    View full text