title: Phase I study of spiroplatin.
abstract: Spiroplatin was investigated in a multicentre phase I study. 67 patients with advanced solid tumours received 151 cycles either by short-term or prolonged infusion, repeated every 3 weeks, at 2.5-40 mg/m2. Myelosuppression and renal toxicity were dose-limiting. Proteinuria, which was dose- and schedule-dependent, indicated glomerular and tubular damage. The maximum tolerated doses (MTD) for poor-risk and good-risk patients were 35 and 40 mg/m2, respectively. The area under the curve (AUC) at the MTD did not correspond with the AUC at the LD10 in mice with ratios of 0.3 for free platinum and 2.6 for total platinum; these were not suitable for predicting the MTD. 1 complete response was observed in a patient with breast cancer and lung metastases and 1 partial response in a patient with adenocarcinoma of the lung. The recommended dose for phase II studies was 30 mg/m2 by 4 h infusion every 3 weeks.
authors.affiliation: Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: B C
authors.initials: BC
authors.lastname: Tanis
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: W W
authors.initials: WW
authors.lastname: ten Bokkel Huinink
authors.forename: I
authors.initials: I
authors.lastname: Klein
authors.forename: H
authors.initials: H
authors.lastname: Gall
authors.forename: A T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: G
authors.initials: G
authors.lastname: Simonetti
authors.forename: J G
authors.initials: JG
authors.lastname: McVie
authors.forename: W J
authors.initials: WJ
authors.lastname: van der Vijgh
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C040757:spiroplatin