Clinical pharmacokinetics of cumulative very high dose of cisplatin in chemotherapy resistant solid tumors.
Cisplatin was administered to seven patients with advanced cancer in divided doses of 40 mg/m2 body surface daily for 5 consecutive days. The pharmacokinetics of total Pt was studied on the days 1, 3 and 5 of infusion. The renal function was assessed through the parameters usually applied in the clinical practice (serum creatinine level, creatinine clearance, urinary volume). Pt pharmacokinetics and the renal function did not show modifications outside the normal range. However, on day 5 of treatment patients showed increased alpha-half life and AUC of plasma Pt, as well as decreased Pt total body clearance and Pt renal clearance, associated to a significant (although still within normal range) increase in serum creatinine and a decrease in urinary volume. Moreover, a correlation between Pt pharmacokinetics and renal parameters (measured as the difference between the values of days 1 and 5 of treatment) was also found: the increase in creatinine was directly related to a decrease in Pt renal clearance and inversely related to Pt peak level in urine, while the latter was inversely related to a reduction of Pt renal clearance. It was concluded that very high doses of cisplatin are well tolerated in patients, although some parameters might suggest early impairment of the renal function.
Tebano
M T
MT
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Rome, Italy.
Carlini
P
P
Loizzo
A
A
Luzi
M
M
Petrucci
F
F
Alimonti
A
A
Caroli
S
S
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy
D000970:Antineoplastic Agents; D002945:Cisplatin