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Phase II trial of gemcitabine plus UFT as salvage treatment in oxaliplatin, irinotecan and fluoropyrimidine-refractory metastatic colorectal cancer

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Abstract

Purpose

To investigate the efficacy of gemcitabine plus uracil–tegafur (UFT) combination chemotherapy as a salvage treatment in patients with metastatic colorectal cancer (MCRC).

Methods

This single-arm phase II study was conducted at three institutions in Korea. Patients with MCRC refractory to fluoropyrimidine, oxaliplatin and irinotecan were enrolled. Gemcitabine 800 mg/m2 was administered intravenously on days 1, 8 and 15. UFT 200 mg/m2/day was taken orally in three divided doses on days 1–21. Cycles were repeated every 4 weeks, and tumor evaluation was carried out every 8 weeks. The primary endpoint of this study was 8-week progression-free survival (PFS) rate.

Results

Forty-one patients were enrolled. Fourteen patients received gemcitabine/UFT as a third-line treatment and 37 patients as a fourth-line or later-line therapy. Toxicities were easily manageable, and non-hematologic toxicities of ≥grade 3 were rare. The most common toxicity of ≥grade 3 was neutropenia (20.0 %). One patient showed partial response (response rate, 2.4 %) and 14 (34.1 %) showed stable disease. The 8-week PFS rate was 42.3 %. The median PFS was 1.7 months [95 % confidence interval (CI) 1.6–1.8 months], and the median overall survival was 9.2 months (95 % CI 5.8–12.6 months).

Conclusions

Overall efficacy of gemcitabine/UFT in refractory MCRC was unsatisfactory. However, we could find a minor proportion of patients who showed prolonged tumor stabilization to gemcitabine/UFT. Further studies are warranted to identify a patient subgroup that might have benefits from gemcitabine/UFT therapy.

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Acknowledgments

This study was supported in part by grants from Yuhan Cooporation (Seoul, Korea). Gemcitabine and UFT were provided by Yuhan Corporation and Jeil Pharmaceutical (Seoul, Korea), respectively. We thank Medical Research Collaborating Center at Seoul National University Hospital for statistical assistance. We are also grateful to Yong Min Shin and Eun-Kyung Kim (Seoul National University Bundang Hospital) for their supports as clinical research coordinators.

Conflict of interest

We declare that we have no conflicts of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-Ro 173 Beon-Gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 463-707, Republic of Korea

    Keun-Wook Lee, Yu Jung Kim & Jee Hyun Kim

  2. Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

    Kyung-Hun Lee, Sae-Won Han, Tae-Yong Kim, Do-Youn Oh, Seock-Ah Im, Tae-You Kim & Yung-Jue Bang

  3. Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea

    In Sil Choi

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  1. Keun-Wook Lee
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Correspondence to Jee Hyun Kim.

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Lee, KW., Kim, Y.J., Lee, KH. et al. Phase II trial of gemcitabine plus UFT as salvage treatment in oxaliplatin, irinotecan and fluoropyrimidine-refractory metastatic colorectal cancer. Cancer Chemother Pharmacol 74, 447–455 (2014). https://doi.org/10.1007/s00280-014-2515-8

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