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Multicenter, randomized study of genetically modified recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in cancer patients receiving chemotherapy

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Abstract

Purpose

The aim of this study is to evaluate the efficacy and safety of genetically modified recombinant human IL-11 (mIL-11), using original IL-11 as an active control, in a multicenter randomized trial involving 88 cancer patients undergoing chemotherapy

Methods

Eighty-eight subjects who had platelets ≦75 × 109/L during the prior chemotherapy were randomized to the MR or RM group. Cohort MR consists of subcutaneous injection of mIL-11 (7.5 μg/kg/day) for 10 days, beginning 72 h after chemotherapy for a 21-day chemotherapy cycle (cycle-1) followed by that of recombinant human interleukin-11 (rhIL-11) (25 μg/kg/day) for another 10 days (cycle-2). Cohort RM represents the reverse sequence. Intent-to-treat populations of mIL-11 (n = 73) or rhIL-11 (n = 80) were analyzed to evaluate the safety.

Results

The incidence of drug-related adverse events of mIL-11 (32.9%) was lower than that of rhIL-11 (51.3%) (p = 0.033). There were no unexpected ≥grade-3 adverse events, and no subject developed antibodies to the mIL-11 protein. Sixty-two subjects were analyzed for efficacy by measuring average platelet levels. Both mIL-11 and rhIL-11 increased nadir platelet levels (62.6 ± 34.9 × 109/L for mIL-11 vs. 60.2 ± 31.7 × 109/L for rhIL-11) as compared with the untreated control group (41.2 ± 17.7 × 109/L) (p < 0.0001). There was no statistical difference in average platelet levels and platelet recovery rate between mIL-11 and rhIL-11.

Conclusions

This study shows that mIL-11 is well tolerated and has thrombopoietic activity equivalent to one third of the clinical dose of rhIL-11, indicating the potential of mIL-11 for use in the treatment of CIT.

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Conflict of interest

Seong-Hyun Ho, Jong-Mook Kim, Seung Shin Yu, and Sunyoung Kim are employees or shareholders of ViroMed Co., Ltd., and Shanshan Ma is an employee of Northland Biotech. The other authors declare no competing financial interests.

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Authors and Affiliations

  1. Cancer Center, 307 Hospital of PLA, No. 8 Dongda Street, Fengtai District, Beijing, China, 100071

    Shikai Wu & Santai Song

  2. The Oncology Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China

    Yang Zhang

  3. The Oncology Department, Beijing Chest Hospital, Beijing, China

    Liyan Xu

  4. The Oncology Department, The First Affiliated Hospital of Soochow University, Suzhou, China

    Yun Dai

  5. Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China

    Yuee Teng

  6. Beijing Northland Biotech. Co., Ltd, Beijing, China

    Shanshan Ma

  7. ViroMed Co. Ltd, Seoul, Republic of Korea

    Seong-Hyun Ho, Jong-Mook Kim, Seung Shin Yu & Sunyoung Kim

  8. School of Biological Sciences, Seoul National University, Seoul, Republic of Korea

    Seong-Hyun Ho & Sunyoung Kim

Authors
  1. Shikai Wu
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  2. Yang Zhang
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  3. Liyan Xu
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  4. Yun Dai
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  5. Yuee Teng
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  6. Shanshan Ma
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  7. Seong-Hyun Ho
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  8. Jong-Mook Kim
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  9. Seung Shin Yu
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  10. Sunyoung Kim
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  11. Santai Song
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Correspondence to Santai Song.

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Wu, S., Zhang, Y., Xu, L. et al. Multicenter, randomized study of genetically modified recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in cancer patients receiving chemotherapy. Support Care Cancer 20, 1875–1884 (2012). https://doi.org/10.1007/s00520-011-1290-x

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  • DOI: https://doi.org/10.1007/s00520-011-1290-x

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