Evaluation of an alternate dosing strategy for cisplatin in patients with extreme body surface area values.
OBJECTIVE
The majority of cytotoxic drugs for adults are dosed based on body surface area (BSA), aiming to reduce interpatient variability in drug exposure. We prospectively studied the usefulness of BSA-based dosing of cisplatin in patients at extremes of BSA values.


METHODS
Patients were randomly assigned to receive a fixed dose of cisplatin in course 1, and a BSA-adjusted dose in course 2, or vice versa. The fixed dose was based on the average BSA for males and females, while extremes were set at BSA values exceeding the average +/- 1 standard deviation. Subsequently, we retrospectively analyzed data from a normal population.


RESULTS
In 25 patients assessable for both courses, the use of a fixed dose of cisplatin resulted in reduced exposure to unbound platinum in patients at the upper extremes of BSA (P = .003) and higher exposures in patients at the lower extremes (P = .009), as compared with exposures following the BSA-adjusted dose. Although clearance was related to BSA (R2 = 0.44; P < .001), only a small reduction in interpatient variability in clearance after correction for BSA was achieved (20.8% v 17.1%). In the retrospective analysis, compared with the average patient, the clearance of unbound platinum in patients with a BSA value < or = 1.65 m2 was 16% slower (P < .001), while an 18% faster clearance (P < .001) was observed in patients with a BSA value > or = 2.05 m2. CONCLUSION Unless better predictors for platinum clearance are identified, fixed-dose regimens per BSA cluster (< or = 1.65 m2; 1.66 m2 to 2.04 m2; > or = 2.05 m2) are recommended.
Department of Medical Oncology, Erasmus MC, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. w.loos@erasmusmc.nl
Walter J
WJ
Loos
Felix E
FE
de Jongh
Alex
A
Sparreboom
Ronald
R
de Wit
Desiree M
DM
van Boven-van Zomeren
Gerrit
G
Stoter
Kees
K
Nooter
Jaap
J
Verweij
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001830:Body Surface Area; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010984:Platinum / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D010984:Platinum; D002945:Cisplatin