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Second-line chemotherapy in patients with advanced or recurrent biliary tract cancer: a single center, retrospective analysis of 294 cases

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Summary

Purpose The survival benefit of first-line chemotherapy (CT1) for biliary tract cancer (BTC) is now established but the role of second-line chemotherapy (CT2) has not been fully elucidated yet. Methods Consecutive advanced BTC patients receiving CT1 between 2000 and 2016 were retrospectively studied. We investigated the safety and efficacy of CT2, prognostic factors for residual survival after CT1, and explored subgroups who would benefit from CT2. Results Among 294 patients receiving CT1 for advanced BTC, CT2 was given in 139 patients (47%). CT2 provided a response rate of 4%, a disease control rate of 52%, a median progression-free survival of 2.8 and overall survival of 7.7 months, respectively. CT2 was associated with longer residual survival after CT1 (hazard ratio [HR] 0.61, p < 0.01), as well as PS of 0–1 (HR 0.53, p < 0.01), best response to CT1 of PD (HR 1.46, p = 0.01), and CEA ≥5.0 ng/mL (HR 1.69, p < 0.01). The effects of CT2 were homogeneous across almost all subgroups but were more prominent in patients with age ≥ 70 years (HR 0.32, p for interaction =0.02), CA19–9 ≥ 200 IU/mL (HR 0.41, p for interaction = 0.08) and CEA ≥5.0 ng/mL (HR 0.41, p for interaction = 0.06). Conclusions The introduction rate of CT2 was 47%. Although the efficacy of CT2 was modest in terms of tumor response, it was associated with better survival. Further investigations are necessary both to develop more effective regimens and to select patients who will benefit from CT2.

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Acknowledgments

N.T.: conception and design of the study; collection, analysis, and interpretation of data; drafting of the article. Y.N. and H.I.: conception and design of the study; collection, analysis, and interpretation of data; critical revision of the article for important intellectual content. K.S., H.O., S.K., T.S., T.S., R.H., K.I., T.T., and T.S.: conception and design of the study; collection, analysis, and interpretation of data. T.S., S.M., H.K. and M. T.: critical revision of the article for important intellectual content. K.K.: critical revision of the article for important intellectual content, and supervision of the study. All authors: final approval of the article.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan

    Naminatsu Takahara, Yousuke Nakai, Kei Saito, Hiroki Oyama, Sachiko Kanai, Tatsunori Suzuki, Tatsuya Sato, Ryunosuke Hakuta, Kazunaga Ishigaki, Tsuyoshi Takeda, Tomotaka Saito, Suguru Mizuno, Hirofumi Kogure, Minoru Tada & Kazuhiko Koike

  2. Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan

    Hiroyuki Isayama

  3. Division of Hepatobiliary and Pancreatic Medicine, Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Takashi Sasaki

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  1. Naminatsu Takahara
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  2. Yousuke Nakai
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  3. Hiroyuki Isayama
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Correspondence to Yousuke Nakai.

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The study was approved by the Ethical Committee of the University of Tokyo Hospital.

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Informed consent was obtained from all individual participants included in the study.

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Takahara, N., Nakai, Y., Isayama, H. et al. Second-line chemotherapy in patients with advanced or recurrent biliary tract cancer: a single center, retrospective analysis of 294 cases. Invest New Drugs 36, 1093–1102 (2018). https://doi.org/10.1007/s10637-018-0670-1

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