title: Neoadjuvant doxil chemotherapy prior to androgen ablation plus radiotherapy for high-risk localized prostate cancer: feasibility and toxicity.
abstract: Patients with clinical T3 or T4 prostate cancer or with elevated serum prostate-specific antigen (PSA) levels greater than 40 ng/ml are at high risk of failure with primary treatment. Chemotherapy administered at the time of diagnosis may decrease the risk of recurrence. Patients with high risk localized prostate cancer were treated with two cycles of liposomal doxorubicin (Doxil) at 50 mg/m2 every 28 days. Patients were assessed for response by digital rectal examination (DRE), PSA, and endorectal magnetic resonance imaging (MRI) (erMRI). Patients were then treated with androgen ablative therapy and prostate radiotherapy. Seven patients were treated. Three patients had T3 disease, and 4 patients had T2b disease with either PSA greater than 40 ng/ml or erMRI evidence of seminal vesicle involvement or extracapsular disease. Median PSA was 29.4 ng/ml. None of the seven patients experienced a significant response, as measured by changes in DRE, PSA, or erMRI. Toxicity was significant, with 4 of 7 patients developing skin toxicity. All seven patients responded to androgen ablative therapy and prostate irradiation. Neoadjuvant liposomal doxorubicin demonstrates no apparent activity and significant toxicity. New strategies are needed to improve outcomes in high-risk prostate cancer.
authors.affiliation: Lank Center for Genitourinary Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.forename: Irving D
authors.initials: ID
authors.lastname: Kaplan
authors.forename: Philip
authors.initials: P
authors.lastname: Febbo
authors.forename: Judith
authors.initials: J
authors.lastname: Prisby
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.forename: Donald S
authors.initials: DS
authors.lastname: Kaufman
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy; D000726:Androgen Antagonists / Q000627:therapeutic use; D000813:Anilides / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000532:radiotherapy; D014105:Tosyl Compounds
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D000903:Antibiotics, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D004317:Doxorubicin; C053541:bicalutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide