A phase I study of lobaplatin (D-19466) administered by 72 h continuous infusion.
A phase I trial with continuous intravenous infusion of lobaplatin (D-19466; 1,2-diamminomethyl-cyclobutane-platinum (II)-lactate) for 72 h was performed to determine the maximum tolerated dose (MTD). Each patient received a single dose level, the total dose of lobaplatin ranged from 30 to 60 mg/m2/72 h every 4 weeks. Eleven patients enroled in this study and received a total of 30 courses of lobaplatin (median 2; range 1-6). Thrombocytopenia was the dose-limiting toxicity, it reached WHO grade III in three out of six patients at 45 mg/m2/72 h, and WHO grade IV in two out of two patients at 60 mg/m2/72 h. Leucocytopenia was mild, as was nausea and vomiting. Phlebitis at the infusion site was found in three patients. During this trial there were no signs of renal, neuro- or ototoxicity. One patient with ovarian cancer, pretreated with three different platinum complexes, achieved a partial response now lasting for longer than 6 months. In conclusion, thrombocytopenia is the dose-limiting toxicity of lobaplatin administered by 72 h continuous infusion. The recommended phase II dose for this regimen is 45 mg/m2/72 h every 4 weeks.
Gietema
J A
JA
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
Guchelaar
H J
HJ
de Vries
E G
EG
Aulenbacher
P
P
Sleijfer
D T
DT
Mulder
N H
NH
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003503:Cyclobutanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010689:Phlebitis / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D003503:Cyclobutanes; D009944:Organoplatinum Compounds; C066228:lobaplatin