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HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with Stage IV Prostate Cancer and Extensive Lung and Bone Metastases

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Abstract

Nanomedicine allows achievement of tumor-selective drug delivery because of the enhanced permeability and retention (EPR) effect of solid tumors. We report here the first clinical application of a new agent—HPMA copolymer-conjugated pirarubicin (P-THP)—with a molecular size of about 8 nm, or 38.5 kDa. A patient had advanced prostate cancer with multiple metastases in the lung, pelvis, femur, and perhaps the sacrum. In April 2013, this 60-year-old patient started treatment with leuprorelin and estradiol, which continued until July 2014, but the patient became refractory to this treatment. So the patient underwent proton beam radiotherapy targeted to the primary prostate cancer, and P-THP was administered for numerous metastatic tumor nodules concomitantly with radiotherapy. This combination therapy had remarkable results, with complete remission of multiple metastases in the lung and bone. The prostate-specific antigen (PSA) value was decreased from about 1000 ng/mL on April 30, 2013, to about 100 ng/mL on June 24, 2013, with hormone therapy, but rose again to 964.2 ng/mL and then to 1472 ng/mL in July 2013, during leuprorelin administration. P-THP treatment administered concomitantly with proton beam irradiation was started in August 2013. The PSA value was decreased to 102 ng/mL on August 26, 2013, and then to 0.971 ng/mL on October 8, 2013, and 0.277 ng/mL on January 15, 2015. The P-THP doses ranged from 30 to 75 mg of free THP equivalent/patient every 2–3 weeks without signs of serious toxicity, such as cardiovascular side effects or a reduction in quality of life. No evidence of relapse was found more than 20 months after P-THP administration. This case demonstrates the value of hydrazone-bonded polymeric drugs in multimodal therapy.

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Notes

  1. EPR-effect: The enhanced permeability and retention (EPR) effect of solid tumors is a unique vascular pathophysiology observed in most solid tumors. It is due to defective vascular architecture and extensive production of vascular permeability factors in tumor tissues, such as nitric oxide, bradykinin, etc. See references [3–6].

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Acknowledgments

The authors thank Phillip Allen Suzuki for critical comments, A. Kovalik for technical assistance, and Judith B. Gandy for editing this paper. Thanks are also due for support from the Adaptable & Seamless Technology Transfer Program through Target-Driven R&D (A-STEP) Research Grants from the Government of Japan, a Grant-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science & Technology (MEXT; No. AS242Z01542Q), a Cancer Specialty Grant from the Japanese Ministry of Health, Welfare and Labor (MHWL), the H23-3rd Cancer Project-General-001 for HM, the Grant Agency of the Czech Republic (grant no. P207/12/J030), and the Ministry of Education, Youth and Sports of the Czech Republic (grant no. EE2.3.30.0029).

Conflict of Interest

None of the authors declared any conflict of interest.

Author information

Authors and Affiliations

  1. Dozono Medical House, Kagoshima, Japan

    Haruhiko Dozono

  2. Department of Obstetrics and Gynecology, National Hospital Organization Kagoshima Medical Center, 8-1 Shiroyama, Kagoshima, 892-0853, Japan

    Shintaro Yanazume

  3. Institute of Drug Delivery Science, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto, 860-0082, Japan

    Hideaki Nakamura, Jun Fang & Hiroshi Maeda

  4. Institute of Macromolecular Chemistry, Academy of Sciences, Prague, Czech Republic

    Tomáš Etrych, Petr Chytil & Karel Ulbrich

  5. Medipolis Proton Therapy and Research Center, Kagoshima, Japan

    Takeshi Arimura

  6. Department of Obstetrics and Gynecology, Kagoshima University School of Medicine, Kagoshima, Japan

    Tsutomu Douchi & Hiroaki Kobayashi

  7. Ikoma Urology Clinic, Kagoshima, Japan

    Michiaki Ikoma

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  1. Haruhiko Dozono
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  2. Shintaro Yanazume
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  3. Hideaki Nakamura
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  7. Jun Fang
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  12. Hiroshi Maeda
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Correspondence to Shintaro Yanazume or Hiroshi Maeda.

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Dozono, H., Yanazume, S., Nakamura, H. et al. HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with Stage IV Prostate Cancer and Extensive Lung and Bone Metastases. Targ Oncol 11, 101–106 (2016). https://doi.org/10.1007/s11523-015-0379-4

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  • DOI: https://doi.org/10.1007/s11523-015-0379-4

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