A phase I study to characterize the safety, tolerability, and pharmacokinetics of topotecan at 4 mg/m2 administered weekly as a 30-minute intravenous infusion in patients with cancer.
Topotecan pharmacokinetics at higher infusion rates (4 mg/m2 over 30 minutes) have not been studied. The authors report a pharmacokinetics and safety study of this dose in advanced cancer patients. Sixteen patients were given a 4-mg/m2 topotecan infusion intravenously (IV) over 30 minutes weekly for 3 weeks, repeated every 28 days. Pharmacokinetics were determined after the first dose. Plasma concentrations of total topotecan were measured to derive CL, V(ss), C(max), t(max), t(1/2), AUC(0-t), and AUC(0-infinity). Plasma total topotecan concentrations decreased biexponentially, with a mean CL value of 20.6 L/h, V(ss) value of 101 L, and t(1/2) value of 5.0 h. Nine significant adverse events (all hematologic) were topotecan related. Grade 3 or less adverse events included anemia, thrombocytopenia, leukopenia, and fatigue. Pharmacokinetics of the 4-mg/m2 infusion of topotecan over 30 minutes are comparable to findings from studies of lower and higher doses. Toxicities are similar to previous reports.
Curtis
Kelly K
KK
Division of Hematology/Oncology, Mayo Clinic, Scottsdale, Arizona 85259, USA.
Hartney
Jean T
JT
Jewell
Roxanne C
RC
Park
Jung W
JW
Lebowitz
Peter F
PF
Griffin
Pamela P
PP
Borad
Mitesh J
MJ
Fitch
Tom R
TR
Northfelt
Donald W
DW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D019772:Topotecan