A Phase II Study of Sequential Capecitabine Plus Oxaliplatin (XELOX) Followed by Docetaxel Plus Capecitabine (TX) in Patients With Unresectable Gastric
Gastric cancer is one of the most frequent cancer types in Taiwan. Advanced gastric cancer
is incurable. Although chemotherapy can improve survival and maintain quality of life for
patients with advanced gastric cancer, optimal chemotherapy for this disease has not been
Cytotoxic agents commonly used in this disease include platinum compounds, fluoropyrimidines
and taxanes. A phase III (V325) study showed that adding docetaxel to cisplatin and 5-FU
(TCF) improved response rates, progression-free survival (PFS), and overall survival (OS).
Although the TCF regimen improved clinical outcomes, it was associated with substantial
toxicity particularly that related to myelosuppression, with a 29% incidence of febrile
neutropenia or neutropenic infection1. Several modifications to the TCF regimen have been
made to maintain efficacy and reduce toxicity.
Cunningham et al. evaluated the impact of substituting oxaliplatin for cisplatin and
capecitabine for 5-FU in the epirubicin, cisplatin, and 5-FU (ECF) regimen. Oxaliplatin as
compared with cisplatin demonstrated comparable efficacy, with a lower incidence of
myelosuppression, thromboembolic complications, and nephrotoxicity. The combination of
docetaxel and oxaliplatin has been evaluated in gastric cancer with moderate activities in
four phase II trials.
A different way of including all active agents in the first line treatment of advanced
gastric cancer is to use them sequentially. Sequential schedules may maximize the
dose-intensity of each single agent and avoid the overlapping toxicity caused by the
concomitant administration of active drugs. Two studies using sequential strategy to treat
advanced gastric cancer were reported.7-8 One used docetaxel after PELF regimen, the other
used cisplatin plus 5-Fluorouracil / leucovorin (5-FU/LV) followed by irinotecan plus
5-FU/LV, followed by docetaxel plus 5-FU/LV. Both studies shown that sequential approach
produced a good treatment efficacy with manageable toxicities in the management of advanced
In our hospital, we had completed two phase II studies in advanced gastric cancer, including
XELOX (capecitabine plus oxaliplatin) and a modified TCF regimen (docetaxel plus cisplatin
and oral tegafur/uracil plus leucovorin). After analyzing these results, the median time to
response, time to progression and overall survival were around 3, 6, and 10 months,
respectively. Overall response rate was around 50% for each.
Based on the above considerations and our previous experiences, we hence initiate this phase
II study to evaluate the feasibility and the anti-tumor activity of a new strategy consists
of two sequential regimens involving XELOX and TX in unresectable gastric cancer.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
objective tumor response rate
Analysis for the objective response rate will be conducted on both the intention-to-treat (ITT) and evaluable data sets. Response will be assessed by Response Evaluation Criteria in Solid Tumor (RECIST 1.1).The analysis will be in descriptive statistics, presented by point estimate and 95% confidence interval for the efficacy variable (Objective tumor response rate)
Yee Chao, MD,PHD
attending physician, cancer center, Taipei Veterans General Hospital
Taiwan : Food and Drug Administration