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Recombinant human soluble thrombomodulin (thrombomodulin alfa) to treat disseminated intravascular coagulation in solid tumors: results of a one-arm prospective trial

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Abstract

Background

Disseminated intravascular coagulation (DIC) associated with solid tumors (DIC-ST) is often encountered in clinical practice. Patients with DIC-ST are usually in poor condition and have bleeding diathesis due to advanced or metastatic diseases. Although some affected patients are treated with heparin, this strategy has not been prospectively studied. Recombinant human soluble thrombomodulin (thrombomodulin alfa, TM-α) is a new anticoagulant developed in Japan. We conducted a prospective study that evaluated the efficacy and safety of TM-α in patients with DIC-ST.

Methods

A prospective one-arm study with TM-α was conducted for DIC-ST. TM-α (380 U/kg) was given for 30 min intravenously once daily for 6–14 days. The primary efficacy endpoint was the DIC resolution rate. Change in DIC scores and improvement in bleeding symptoms and outcomes were also evaluated. Safety endpoints included the incidence of bleeding-related adverse events.

Results

A total of 101 patients were treated with TM-α. The three main underlying malignant diseases were lung, stomach, and breast cancer, which accounted for 60 % of all patients. The DIC resolution rate was 34.0 % at the end of TM-α treatment. Improvement in DIC scores was seen in 55.2 % of patients, while only 22.9 % of patients had worsening of DIC scores. The overall survival rate was 55.4 % on day 28. The incidence of hemorrhage related to TM-α was 12.9 % until day 28. Cases of severe hemorrhage related to TM-α did not occur.

Conclusions

TM-α is effective and safe for DIC-ST. This agent is the treatment of choice for the management of DIC-ST.

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Acknowledgments

This work was supported by Asahi Kasei Pharma Corporation (AKP). In addition to the authors, 34 institutions participated in this study. The institutions and investigators are shown in Table 7. The authors have access to all primary data, which can be made available to the journal editors upon request.

Conflict of interest

K. Tamura, H. Saito and N. Aoki have received consultancy funding from AKP. H. Asakura and K. Okamoto have received lecture fees from AKP. J. Tagawa and T. Hayakawa are employees of AKP.

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Authors and Affiliations

  1. Division of Medical Oncology, Hematology and Infectious Diseases, Department of Medicine, Fukuoka University Hospital, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, Fukuoka, 814-0180, Japan

    Kazuo Tamura

  2. National Hospital Organization Nagoya Medical Center, 4-1-1, Sannomaru, Naka-ku, Nagoya, Aichi, 460-0001, Japan

    Hidehiko Saito

  3. Third Department of Internal Medicine, Kanazawa University Graduate School of Medical Science, 13-1, Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan

    Hidesaku Asakura

  4. Center for Gastroenterology and Liver Disease, Kitakyushu Municipal Yahata Hospital, 4-18-1, Nishihonmachi,Yahatahigashi-ku, Kitakyushu, Fukuoka, 805-0061, Japan

    Kohji Okamoto

  5. Clinical Development Center, Asahi Kasei Pharma Corporation, 1-105, Kanda Jinbocho, Chiyoda-ku, Tokyo, 101-8101, Japan

    Jun Tagawa & Toru Hayakawa

  6. Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Nobuo Aoki

Authors
  1. Kazuo Tamura
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  2. Hidehiko Saito
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  3. Hidesaku Asakura
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  4. Kohji Okamoto
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  5. Jun Tagawa
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  6. Toru Hayakawa
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  7. Nobuo Aoki
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Corresponding author

Correspondence to Kazuo Tamura.

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Tamura, K., Saito, H., Asakura, H. et al. Recombinant human soluble thrombomodulin (thrombomodulin alfa) to treat disseminated intravascular coagulation in solid tumors: results of a one-arm prospective trial. Int J Clin Oncol 20, 821–828 (2015). https://doi.org/10.1007/s10147-014-0768-1

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  • DOI: https://doi.org/10.1007/s10147-014-0768-1

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