Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study

Wenhua Li, Xiaoying Zhao, Huijie Wang, Xin Liu, Xinmin Zhao, Mingzhu Huang, Lixin Qiu, Wen Zhang, Zhiyu Chen, Weijian Guo, Jin Li, Xiaodong Zhu, Wenhua Li, Xiaoying Zhao, Huijie Wang, Xin Liu, Xinmin Zhao, Mingzhu Huang, Lixin Qiu, Wen Zhang, Zhiyu Chen, Weijian Guo, Jin Li, Xiaodong Zhu

Abstract

Background: Maintenance therapy proves to be effective in advanced lung and breast cancer after initial chemotherapy. The purpose of this phase II study was to evaluate the efficacy and safety of Uracil and Tegafur (UFT) maintenance in metastatic gastric cancer patients following the first-line fluorouracil-based chemotherapy.

Methods: Metastatic gastric cancer patients with stable disease or a better response after the completion of first-line chemotherapy were randomized to oral UFT (360mg/m2 × 2 weeks) every 3 weeks until disease progression/intolerable toxicity or to observation (OBS). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS) and safety.

Results: The trial was closed after the interim analysis of the 58 enrolled (120 planned) patients. Median PFS was not improved in the UFT group compared with the OBS group (3.2 months versus 3.6 months, P = 0.752), as well as the median OS (14.2 months for both, P = 0.983). However, subgroup analysis showed that low baseline hemoglobin (< 120 g/L) was associated with poorer PFS with maintenance therapy (P = 0.032), while the normal hemoglobin patients benefit from the UFT treatment (P = 0.008). Grade 3 to 4 toxicities in the UFT group were anemia (3.4%), thrombocytopenia (3.4%) and diarrhea (6.9%).

Conclusions: This trial did not show superiority of UFT maintenance in non-selected patients responding to fluorouracil-based first-line chemotherapy. The normal hemoglobin level at baseline is a predictive biomarker for favorable patient subsets from the maintenance treatment.

Keywords: UFT; chemotherapy; gastric carcinoma; maintenance treatment.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no competing interests.

Figures

Figure 1. Kaplan-Meier estimates of progression-free survival…
Figure 1. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS)
A. Median PFS was 3.2 months in UFT group compared with 3.6 months in observation group. B. Median OS was 14.2 months in both UFT group and observation group.
Figure 2. Kaplan-Meier curves of progression-free survival…
Figure 2. Kaplan-Meier curves of progression-free survival (PFS) and overall survival (OS) by baseline hemoglobin subgroup
In patients with low hemoglobin level (A. median PFS was 1.9 months in UFT group compared with 3.6 months in observation group, and B. median OS was 14.0 months in UFT group compared with 21.2 months in observation group; In patients with normal hemoglobin level (≥ 120 g/L), C. median PFS was 7.1 months in UFT group compared with 2.4 months in observation group, and D. median OS was 23.6 months in UFT group compared with 10.5 months in observation group.

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