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)

• Published in: Investigational new drugs Vol. 23; no. 1; pp. 79 - 84
• Main Authors: Latif, Tahir, Wood, Laura, Connell, Cindy, Smith, David C, Vaughn, David, Lebwohl, David, Peereboom, David
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01-01-2005
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; Androgens; Antigens; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Cancer therapies; Chemotherapy; Creatinine; Cytotoxicity; Drug Administration Schedule; Hematology; Humans; Male; Maximum Tolerated Dose; Medical prognosis; Metastasis; Middle Aged; Neoplasms, Hormone-Dependent - drug therapy; Oncology; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Patients; Prostate cancer; Prostate-Specific Antigen - metabolism; Prostatic Neoplasms - drug therapy; Response rates; Safety; Thrombocytopenia; Treatment Outcome; Urinalysis; X-rays
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1023/b:drug.0000047109.76766.84

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.