title: Phase II study of oral bis (aceto) ammine dichloro (cyclohexamine) platinum (IV) (JM-216, BMS-182751) given daily x 5 in hormone refractory prostate cancer (HRPC).
abstract: JM-216 is an orally bioavailable platinum compound with activity against many tumor models. The objective of this study was to determine the safety profile and anti-tumor activity of JM-216 in patients with hormone refractory prostate cancer (HRPC) when given orally daily x 5 days. In this open label phase II study JM-216 was administered orally at the dose of 120 mg/m2/d for 5 days every 4 weeks. Patients continued on the therapy until evidence of disease progression or intolerable toxicity developed. Dose escalation and de-escalation were allowed according to patient's tolerance. Thirty-nine patients were enrolled onto the study and received a total of 155 courses (median 2, range 1-16) of JM-216. Dose delays (77% of courses) and dose reductions (31% of courses) were common and were mainly due to myelosupression. Treatment was discontinued in 5 patients due to treatment related toxicities. One patient developed myelodysplastic syndrome 11 months after the start of treatment. The most frequent grade III or higher adverse events included thrombocytopenia (54%), neutropenia (52%), anemia (24%) nausea (13%), vomiting (16%) and diarrhea (28%). PSA response was assessed in 32 patients, 10 (26%) had partial response, 14 (36%) had stable disease while PSA progression was seen in 8 (21%) patients. Of 20 (54%) patients with measurable disease two patients had a documented partial response. Although JM-216 had moderate activity in HRPC when given on daily basis for 5 days, it is associated with significant treatment related toxicities in this patient population.
authors.affiliation: Department of Hematology and Medical Oncology, Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland OH 44195, USA.
authors.forename: Tahir
authors.initials: T
authors.lastname: Latif
authors.forename: Laura
authors.initials: L
authors.lastname: Wood
authors.forename: Cindy
authors.initials: C
authors.lastname: Connell
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Vaughn
authors.forename: David
authors.initials: D
authors.lastname: Lebwohl
authors.forename: David
authors.initials: D
authors.lastname: Peereboom
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012449:Safety; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C081294:satraplatin; D017430:Prostate-Specific Antigen