Conversion Surgery Post-Intraperitoneal Paclitaxel and Systemic Chemotherapy for Gastric Cancer Carcinomatosis Peritonei. Are We Ready?

Abstract

Peritoneal metastasis is common in gastric cancer. It is difficult to treat and carries a poor prognosis. Intraperitoneal (IP) delivery of chemotherapy can attain a higher drug exposure in the peritoneal cavity but with reduced systemic toxicity. Therefore, we hypothesized that IP paclitaxel with systemic chemotherapy would be clinically beneficial for gastric cancer with peritoneal metastases. Patients with unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology were recruited. They underwent eight cycles of IP paclitaxel and systemic XELOX. The primary endpoint was 1-year overall survival rate and secondary endpoints were safety, response rate, and peritoneal cytological response. Patients who subsequently had no distant metastases and two consecutive negative peritoneal cytologies underwent conversion gastrectomy if there was no macroscopic evidence of peritoneal disease at diagnostic laparoscopy. Twenty-two patients were enrolled, receiving at least one cycle of IP paclitaxel at the time of reporting (data cutoff-March 11, 2016). The median number of cycles was 7.5. The median overall survival was 18.8 months, and the 1-year survival rate was 72.2%. One patient died of neutropenic sepsis. Of 19 evaluable patients with measurable disease, 7 (36.8%) achieved PR, 8 (42.1%) achieved SD, and 4 (21.1%) experienced PD. Peritoneal cytology turned negative in 11 of 17 (64.7%) patients. Six patients underwent conversion gastrectomy (4 R0, 2 R1) with a median survival of 21.6 months (range = 8.7-29.9 months). XELOX and IP paclitaxel appears to be an effective regimen in gastric cancer with peritoneal metastases. Conversion gastrectomy may be considered in patients with a favorable response.

Metastatic gastric cancer: Does the site of metastasis make a difference?

“…Several retrospective and prospective series have demonstrated the efficacy of the upfront use of these therapies in the management of isolated gastric peritoneal metastasis, achieving median survival of up to 24.6 months and 1‐year overall survival rates as high as 91% . Recognizing that such treatment approaches come with their attendant morbidities, in an attempt to refine the selection of patients who may best benefit from aggressive locoregional therapies, another related investigational staged treatment approach, conversion surgery, is currently being explored . This approach subjects patients to concomitant systemic and intraperitoneal chemotherapy upfront before selecting the subgroup with complete peritoneal metastatic remission to undergo subsequent “conversion gastrectomy,” achieving median survival rates of 21.6 months in a small prospective series .…”

“…Recognizing that such treatment approaches come with their attendant morbidities, in an attempt to refine the selection of patients who may best benefit from aggressive locoregional therapies, another related investigational staged treatment approach, conversion surgery, is currently being explored . This approach subjects patients to concomitant systemic and intraperitoneal chemotherapy upfront before selecting the subgroup with complete peritoneal metastatic remission to undergo subsequent “conversion gastrectomy,” achieving median survival rates of 21.6 months in a small prospective series . In addition, in the specific patient subgroup with CY+P0 metastatic disease, EIPL has been studied as a promising and effective strategy in improving long‐term overall survival …”

“…In the field of metastatic gastric cancer, prospective series examining patients with isolated peritoneal metastasis have demonstrated efficacy of similar multimodality treatment approaches, yielding median overall survival in the range of 14.4–24.6 months . In addition, in the case of gastric cancer with positive peritoneal cytology but without overt peritoneal metastases (CY+P0), extensive intraoperative peritoneal lavage (EIPL) has been studied with promising results .…”

“…In addition, in the case of gastric cancer with positive peritoneal cytology but without overt peritoneal metastases (CY+P0), extensive intraoperative peritoneal lavage (EIPL) has been studied with promising results . Apart from offering the possibility of prolonged survival, these modalities may offer palliation from peritoneal metastases that we postulate would result in significant symptoms if treated with systemic chemotherapy or best supportive care alone …”

Clinical significance of conversion surgery for gastric cancer with peritoneal dissemination: A retrospective study

“…To date, several investigators have reported the clinical utility of conversion surgery after chemotherapy among patients with colorectal, pancreatic, esophageal, and gastric cancer [10][11][12][13]. Unfortunately, only a few studies have been conducted on conversion surgery among responders with P1 gastric cancer after chemotherapy [14][15][16]. Hence, the clinical impact of conversion surgery remains unclear among patients with peritoneal dissemination of gastric cancer.…”