INTRA-PERITONEAL PACLITAXEL IN COMBINATION WITH SYSTEMIC XELOX FOR GASTRIC CANCER WITH PERITONEAL METASTASES: RESULTS FROM A SINGAPOREAN PHASE II TRIAL
Daryl K. Chia*1, Raghav Sundhar2, Jia Jun Ang1, Guo Wei Kim1, Hon-Lyn Tan2, Cheng Ean Chee2, Asim Shabbir1, Wei Peng Yong2, Jimmy B. So1
1Department of Surgery, National University Health System (NUHS), Singapore, Singapore; 2Department of Haematology-Oncology, National University Health System (NUHS), Singapore, Singapore
Introduction.
Peritoneal metastasis (PM) is common in gastric cancer (GC) and carries a dismal prognosis. Promising results have been reported with intra-peritoneal (IP) chemotherapy, especially in patients with good response who could undergo conversion surgery. We conducted a phase II trial (NCT01739894) to assess the efficacy of combining systemic XELOX with IP paclitaxel (PTX) in GCPM patients.
Methods.
GC patients with PM and no extra-peritoneal disease were prospectively recruited and received IP paclitaxel with systemic XELOX. The primary endpoint was median overall survival and secondary endpoints included 1-year overall survival, surgical outcomes and safety data. Common Terminology Criteria for Adverse Events (CTCAE) v.4 was used to grade adverse events. Patients were considered eligible for conversion gastrectomy if they had no disease progression, negative cytology on 2 consecutive assessments and no PM on diagnostic laparoscopy. Outcomes was compared against a retrospective cohort of 32 GCPM patients who received oxaliplatin-based systemic chemotherapy.
Results.
Of 45 patients recruited for the trial, 84% (38) had newly diagnosed GCPM and 16% (7) had recurrent PM after prior gastrectomy. (Fig. 1) The median overall survival (OS) in GCPM patients receiving IP PTX with XELOX was not superior when compared against a retrospective cohort of GCPM patients with similar baseline demographic characteristics who received oxaliplatin-based systemic chemotherapy. (Figure 2, median OS (months, [IQR]), IP vs. oxaliplatin group, 14.9 [IQR: 11.0-24.3] vs. 13.5 [IQR: 6.0-25.2] months, p=0.799) The 1-year survival rate was higher in the IP group (IP vs. oxaliplatin, 60% vs. 34.4%, p<0.038). Of those who had newly diagnosed GCPM, 34% (13/38) underwent conversion gastrectomy with a 1-year survival rate of 76.9% (10/13) and had superior median OS (months, [IQR]) compared to inoperable GCPM patients. (Conversion gastrectomy vs. inoperable group, 24.3 [18.6-33.7] vs. 13.0 [7.1-15.2] months, p=0.018). 30.8% (4/13) of those who underwent conversion gastrectomy experienced major morbidity and 54% (7/13) had R0 margins while 46% (6/13) had microscopically positive (R1) margins. The 1-year survival rate was higher in the R0 group but did not reach statistical significance. (R0 vs. R1, 100% vs. 57%, p=0.192) A total of 594 cycles of IP chemotherapy were administered during the trial, with the incidence of CTCAE grade 3, 4 and 5 complications being 5.6% (33), 0.7% (4) and 0.4% (2) respectively.
Conclusion.
Combination IP paclitaxel and systemic XELOX is feasible, has a low rate of severe adverse events and improves 1-year survival rates when compared with systemic oxaliplatin-based chemotherapy. The greatest survival benefit was observed in patients who underwent conversion gastrectomy.
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