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Outcomes of Intraperitoneal and Systemic Chemotherapy for Patients with Peritoneal Metastases from Gastric Cancer: Is Conversion Surgery Possible?
Dexter Y. Chan*1, Nicholas L. Syn2,3, Rachel Yap2, Janelle N. Phua1, Amy Yuh Ling Tay1, Asim Shabbir1, Thomas I. Soh2,3, Jimmy B. So1, Wei-Peng Yong2,3
1Division of General Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore, Singapore; 2Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore; 3Cancer Science Institute of Singapore, National University of Singapore Centre for Translational Medicine, Singapore, Singapore

Aim: Peritoneal metastasis is common in gastric cancer. It is difficult to treat medically and is associated with grave prognosis. Studies have shown increased drug concentration in the peritoneal cavity when chemotherapy is administered via the intraperitoneal (IP) route. We therefore hypothesized that IP paclitaxel plus XELOX may yield clinical benefit in gastric cancer with peritoneal metastases.
Methods: Patients with histologically-confirmed, unresectable and/or recurrent gastric adenocarcinoma with peritoneal dissemination and/or positive peritoneal washing cytology, not previously-treated or received prior systemic therapy > 180 days ago, and ECOG ≤ 2 are eligible. Patients were treated with paclitaxel 40 mg/m2 IP on days 1 and 8, oxaliplatin 100 mg/m2 IV over 2 hours on day 1, and capecitabine 1000 mg/m2 b.i.d. PO for 2 weeks followed by 1 week of rest. This was repeated for 8 cycles. The primary endpoint is 1-year overall survival rate and the secondary endpoints are safety, response rate and peritoneal cytological response. Pre-planned target sample size is 20. Patients who subsequently have no distant metastases, with stable or reduced peritoneal disease and 2 consecutive negative peritoneal cytologies would then be eligible for conversion gastrectomy.
Results: Table 1 shows key clinicopathological characteristics at baseline. 22 patients have been enrolled, received at least one cycle at the time of reporting (data cutoff: 14 Nov 2015) and are eligible for analysis. Median no. of cycles is 5 (range: 1 - 8). Median OS is 557 days and 1-year survival rate is 69.2%. (Fig.1) Of 16 evaluable pts with measurable disease, 6 (37.5%) achieved PR, 7 (43.8%) achieved SD and 3 (18.8%) experienced PD. Peritoneal cytology turned negative in 12 of 15 (80%) pts. Severe (grade ≥ 3) AEs were primarily limited to leukopenia (N = 2; 10%), neutropenia (N = 4; 20%), thrombocytopenia (N = 2), hand-foot syndrome (N = 2), bacterial peritonitis (N = 2) and hypokalaemia (N = 4). Complications seen were neutropenic sepsis (N = 2) which led to 1 death, tumor perforation (N = 1) and infection at the port-site (N = 1). Frequent mild AEs seen were fatigue, nausea, diarrhoea, anorexia and sensory neuropathy. Five patients underwent conversion gastrectomy (3 R0, 2 R1) with no additional morbidity. All of these patients lived past 1 year
Conclusions: XELOX + IP paclitaxel appears to be a well-tolerated and active regimen in gastric cancer with peritoneal metastases, and may offer survival benefits. Finally, conversion gastrectomy may be considered in patients with favourable response.
Table 1. Patient characteristics (N = 22)
Age (years) 
Median61
Range45-75
Gender 
Female9 (40.9%)
Male13 (59.1%)
Performance status (ECOG) 
011 (50%)
19 (40.9%)
22 (9.1%)
Histological Subtype 
Diffuse13 (59.1%)
Intestinal4 (18.2%)
Mixed5 (22.7%)
Degree of peritoneal metastasis 
P14 (18.2%)
P24 (18.2%)
P314 (63.6%)
Other metastatic sites 
Ovary1 (4.5%)
Bowel serosa4 (18.2%)
Omentum14 (63.6%)
Lymph node18 (81.8%)
Baseline cytology 
Positive19 (86.4%)
Ascites 
Present14 (63.4%)
Prior treatment 
Chemotherapy (> 180d)2 (9.1%)
Gastrectomy5 (22.7%)

Figure 1. Kaplan-Meier plot for 1-year overall survival (n = 13 )


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