A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support.
A series of 33 patients were treated with a four-day continuous infusion of carboplatin in a phase I study to determine the maximum-tolerated dose (MTD) of this agent when used with autologous bone marrow reinfusion. Doses were escalated from 375 to 2,400 mg/m2; autologous bone marrow reinfusion was added to the regimen at doses of 1,600 mg/m2 and above. The MTD was determined to be 2,000 mg/m2. Dose-limiting toxicity consisting of reversible hepatotoxicity, renal dysfunction, and moderate to severe ototoxicity was observed with a dose of 2,400 mg/m2. There were ten responses in 31 heavily pretreated patients, including six responses in 11 patients with recurrent ovarian cancer. Pharmacokinetic studies revealed a systemic clearance (Clss) of 4.5 L/m2/h. This value is consistent with clearances reported for carboplatin administered at lower doses and by different schedules. No evidence for saturation of systemic clearance at higher doses was observed. Carboplatin appears to be an active drug that can undergo considerable dose escalation when used in conjunction with autologous bone marrow support.
Shea
T C
TC
Solid Tumor Autologous Marrow Program, Dana-Farber Cancer Institute, Boston.
Flaherty
M
M
Elias
A
A
Eder
J P
JP
Antman
K
K
Begg
C
C
Schnipper
L
L
Frei
E
E
Henner
W D
WD
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D016026:Bone Marrow Transplantation; D016190:Carboplatin; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D010984:Platinum / Q000097:blood / Q000652:urine
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D010984:Platinum; D016190:Carboplatin