title: HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with Stage IV Prostate Cancer and Extensive Lung and Bone Metastases.
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.
authors.affiliation: Dozono Medical House, Kagoshima, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Dozono
authors.affiliation: Department of Obstetrics and Gynecology, National Hospital Organization Kagoshima Medical Center, 8-1 Shiroyama, Kagoshima, 892-0853, Japan. s-yana@kagomc2.hosp.go.jp.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yanazume
authors.affiliation: Institute of Drug Delivery Science, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto, 860-0082, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Etrych
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Chytil
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences, Prague, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
authors.affiliation: Institute of Drug Delivery Science, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto, 860-0082, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.affiliation: Medipolis Proton Therapy and Research Center, Kagoshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arimura
authors.affiliation: Department of Obstetrics and Gynecology, Kagoshima University School of Medicine, Kagoshima, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Douchi
authors.affiliation: Department of Obstetrics and Gynecology, Kagoshima University School of Medicine, Kagoshima, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Ikoma Urology Clinic, Kagoshima, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Ikoma
authors.affiliation: Institute of Drug Delivery Science, Sojo University, Ikeda 4-22-1, Nishi-ku, Kumamoto, 860-0082, Japan. hirmaeda@ph.sojo-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D008689:Methacrylates / Q000737:chemistry*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D008689:Methacrylates; D004317:Doxorubicin; C027260:pirarubicin; C032802:hydroxypropyl methacrylate