Feasibility Study of Intraperitoneal Paclitaxel With Oxaliplatin and Capecitabine in Patients With Advanced Gastric Cancer
The median survival of patients with unresectable gastric cancer treated with systemic
chemotherapy is about 12 months. In patients with histologically proven unresectable or
recurrent gastric cancer limited to the peritoneum and/or cancer cells in peritoneal
cytology, the combination of i.p. paclitaxel with systemic chemotherapy reported a median
survival time of 23.6 months. The peritoneal cytology turned negative for 86% of patients.
In an updated report, gastrectomy was performed on 52 patients after disappearance or
obvious shrinkage of peritoneal metastasis. In this cohort, the median survival time (MST)
was 34.9 months. A phase III trial (PHOENIX-GC trial (Phase III study of S-1 plus
intravenous and intraperitoneal paclitaxel versus S-1 plus cisplatin for gastric cancer with
peritoneal metastasis )) comparing intraperitoneal(IP) regimen with systemic chemotherapy
versus systemic therapy alone is currently opened for recruitment in Japan.
The multidisciplinary treatment combining IP-containing chemotherapy and surgery was found
to be safe and effective for gastric cancer patients with peritoneal metastasis. A phase I
study combining i.p. paclitaxel with oxaliplatin and S-1, found no dose limiting toxicity in
all dose levels. Grade 3 neutropenia was observed in one patient at recommended phase 2 dose
(RP2D) of i.p. paclitaxel of 40 mg/m2. In addition, grade 2 non-hematological toxicities
observed were anorexia (n=6/12), fatigue (n=4/12) and nausea (n=2/12).
Both S-1 and capecitabine are orally available fluoropyrimidine. When combined with
oxaliplatin, both S-1 and capecitabine were found to be equally active and well tolerated in
advanced gastric cancer patients. As S-1 is not yet widely available worldwide, the
combination of capecitabine and a platinum chemotherapy is still one of the most commonly
adopted chemotherapy regimen for patients with advanced gastric cancer. In this study, we
intend to assess the efficacy and feasibility of combining weekly i.p. paclitaxel with
oxaliplatin and capecitabine.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall survival (OS) rate
The primary end point is 1-year survival because most patients may not have measurable disease, hence response rate and progression free survival are less easy to assess.
Wei Peng Yong, MBBS
National University Hospital, Singapore
Singapore: Domain Specific Review Boards