Neoadjuvant Chemotherapy With Xeloda in Combination With Paclitaxel in Gastric Cancer With Liver Metastasis
Patients with advanced or metastatic gastric cancer have a poor prognosis. The optimal
treatment of gastric cancer with liver metastases without other distant metastases remains a
matter for debate and there are few prospective clinical trials to explore this area. The
aim of this prospective phase II study is to evaluate the optimal treatment of gastric
cancer with liver metastases.
In preclinical xenograft models, capecitabine was highly active against several tumors,
including breast, colorectal, gastric, and cervical tumors, and against both 5-FU-sensitive
and 5-FU-resistant tumors. Intermittent capecitabine (1250 mg/m2 daily dose for 14 days,
followed by a 7-day rest period) was shown to be active as a single agent in previously
untreated AGC patients, with a response rate of 28.2% in 39 patients. The combination of
capecitabine with other drugs, such as cisplatin, oxaliplatin, epirubicin, and docetaxel,
had an objective response rate of 40-68% as first-line treatment in patients with AGC.
In human colon cancer xenograft model, thymidine phosphorylase is upregulated and synergy
between paclitaxel and capecitabine has been observed. The activity of capecitabine in
patients with breast cancer refractory to paclitaxel and anthracyclines suggests that the
combination of capecitabine and paclitaxel may be effective in treating patients with
advanced breast cancer. Doses recommended are capecitabine 1650 mg/m2 per day orally for 14
days and paclitaxel 175 mg/m2 i.v. every 3 weeks.
In a phase II trial with 45 patients involved, 2 patients showed complete response and 20
showed partial response making the overall response rate 48.9% (95%CI:30.3-63.5%). There was
no neutropaenic fever or treatment-related deaths. That study demonstrated that paclitaxel
and capecitabine combination chemotherapy was active and highly tolerable.
The rationale of this study was to find out if outcome could be improved after neoadjuvant
chemotherapy with paclitaxel and capecitabine with or without local treatment for patients
without other distant metastasis than liver metastasis.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Tumor response will be evaluated using RECIST criteria. Survival data will be analyzed by Kaplan Meier method. 95% CI will be provided
Primary Endpoint is PFS (progression free survival), tumor response will be evaluated using RECIST criteria. Survival data will be analyzed by Kaplan Meier method. 95% CI will be provided.
3 years from last patient enrolled
Jiafu Ji, Post-Doctor
Beijing Cancer Hospital
China: Food and Drug Administration