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Evaluation of the safety and pathological effects of neoadjuvant full-dose gemcitabine combination radiation therapy in patients with biliary tract cancer

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Abstract

Purpose

This study aimed to evaluate the safety of neoadjuvant gemcitabine combination radiation therapy in the treatment of biliary tract cancer and to investigate the pathological effects of chemoradiation therapy and its impact on survival.

Methods

Chemoradiation therapy entailed three cycles of full dose of gemcitabine (1000 mg/m2 at days 1, 8, and 15, every 4 weeks) with 50–60 Gy radiation (2 Gy/day) at the main tumor and the regional and para-aortic lymph nodes. The present study included 25 patients.

Results

All of the patients were pathologically diagnosed before treatment. The relative dose intensity of gemcitabine was 84 %. The average dose of radiation was 53.8 Gy. Sixty percent of the patients underwent pancreatoduodenectomy, and 32 % underwent hemi-hepatectomy due to bile duct cancer (n = 24) or gall bladder cancer (n = 1). During neoadjuvant therapy, 21 patients (84 %) suffered from adverse events. The common hematological adverse events were leukopenia (44 %) and thrombocytopenia (32 %). It was necessary to exchange the plastic biliary stent in 11 patients (44 %). An R0 resection was achieved in 96 % of the patients, with pathological lymph node metastasis noted in 16 %. Moderate or marked histological changes were noted in 32 % of the patients. The 3-year overall survival rate after the first treatment was 74.6 %, with a 3.2-year observation period.

Conclusions

Neoadjuvant therapy was feasible and is expected to improve survival by controlling regional extension.

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Abbreviations

BTC:

Biliary tract cancer

CA19-9:

Carbohydrate antigen 19-9

CEA:

Carcinoembryonic antigen

CTCAE:

Common toxicity criteria adverse events

OS:

Overall survival

PVE:

Portal vein embolization

RFS:

Recurrence-free survival

UICC:

International Union Against Cancer

ULN:

Upper limit of normal

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Authors’ contributions

Shogo Kobayashi, Kunihito Gotoh, Terumasa Yamada, Hiroaki Ohigashi, Osamu Ishikawa, and Kinji Nishiyama involved in the study conception and design. Shogo Kobayashi, Kunihito Gotoh, Hidenori Takahashi, Hirofumi Akita, Shigeru Marubashi, Terumasa Yamada, Teruki Teshima, and Kinji Nishiyama involved in data acquisition. Shogo Kobayashi, Akira Tomokuni, Kunihito Gotoh, Hidenori Takahashi, Hirofumi Akita, Masahiko Yano, Hiroaki Ohigashi, Osamu Ishikawa, and Masato Sakon involved in data analysis and interpretation. Shogo Kobayashi drafted the manuscript. Teruki Teshima, Hiroaki Ohigashi, Osamu Ishikawa, and Masato Sakon critically revised the paper.

Funding

This study was funded by a Grant-in-Aid for Scientific Research (C, 15K10202).

Author information

Authors and Affiliations

  1. Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamichi 1-3-3, Higashinari-ku, Osaka City, Osaka, 537-8511, Japan

    Shogo Kobayashi, Akira Tomokuni, Kunihito Gotoh, Hidenori Takahashi, Hirofumi Akita, Shigeru Marubashi, Terumasa Yamada, Masahiko Yano, Hiroaki Ohigashi, Osamu Ishikawa & Masato Sakon

  2. Department of Surgery and Radiation Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Teruki Teshima & Kinji Nishiyama

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  1. Shogo Kobayashi
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  2. Akira Tomokuni
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Corresponding author

Correspondence to Shogo Kobayashi.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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

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Kobayashi, S., Tomokuni, A., Gotoh, K. et al. Evaluation of the safety and pathological effects of neoadjuvant full-dose gemcitabine combination radiation therapy in patients with biliary tract cancer. Cancer Chemother Pharmacol 76, 1191–1198 (2015). https://doi.org/10.1007/s00280-015-2908-3

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  • DOI: https://doi.org/10.1007/s00280-015-2908-3

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