title: [Phase I study of a new platinum complex 254-S, cis-diammine (glycolato)-platinum (II)].
abstract: A new platinum complex 254-S had a superior preclinical therapeutic indices compared to cisplatin, showing decreased renal and gastrointestinal toxicities. Phase I clinical study with a single dose schedule was conducted to investigate the safety, toxicity, pharmacokinetics and possible efficacy against various advanced cancers by a cooperative study of 10 institutions. The drug was administered by i.v. infusion for 60 min dissolved in 250 ml of 5% xylitol solution, without the use of hydration and antiemetics. At least 3 patients at each dose level of 10, 20, 40, 80, 100 and 120 mg/m2 were tested and 28 patients were entered into this study. Myelosuppression, especially thrombocytopenia, appeared strongly at dose level of 80 mg/m2 and dose limiting thrombocytopenia was found in 2 of 5 patients. Leukocytopenia was also dose-related but moderate. Platelet and WBC nadirs occurred around 3 weeks after administration with recovery in about one week. Although slight elevation of BUN and creatinine were temporarily observed in a few cases, no significant renal toxicity was observed. Anorexia, nausea and vomiting were observed in the majority of patients, but milder than cisplatin. In conclusion, 254-S has demonstrated reduced non-hematologic toxicities as compared to cisplatin. This drug appears to be well tolerated and 120 mg/m2 was maximum tolerated dose. The recommended dose for phase II studies was thought to be 100 mg/m2 by i.v. infusion every 4 weeks.
authors.affiliation: Dept. of Internal Medicine, Aichi Cancer Center, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ota
authors.forename: A
authors.initials: A
authors.lastname: Wakui
authors.forename: H
authors.initials: H
authors.lastname: Majima
authors.forename: H
authors.initials: H
authors.lastname: Niitani
authors.forename: Y
authors.initials: Y
authors.lastname: Inuyama
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ariyoshi
authors.forename: O
authors.initials: O
authors.lastname: Yoshida
authors.forename: T
authors.initials: T
authors.lastname: Taguchi
authors.forename: I
authors.initials: I
authors.lastname: Kimura
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C053989:nedaplatin