D. Cupissol et al., VALIDATION OF A NEW INTERACTIVE SOFTWARE MONITORING A CONTROLLED-FLOWINFUSION-PUMP FOR CISPLATIN DOSAGE REGIMEN ADJUSTMENT, Bulletin du cancer, 83(8), 1996, pp. 664-676
Adaptive dosing of cisplatin (CDDP) results in reduced haematological
and renal toxicity but it has never been clearly shown that it affects
the tumoral response rate. Before undertaking a clinical randomized s
tudy of CDDP monitoring versus standard dose, a comparative study was
performed between a new software dedicated to the interactive adjustme
nts - the AJI software - and the APIS software for clinical pharmacoki
netics which incorporates a bayesian procedure and a population inform
ation computed according to a three compartment model. CDDP was admini
stered by continuous infusion at variable rates with a controlled flow
pump during four days in order to reach the target of 1.3 mg/L at the
end of the first day, and to maintain this level during the whole tre
atment. This study was carried our on two groups of patients. Group I
(12 patients; 27 courses) received CDDP with sequential flow rates in
order to obtain a population information to be used with AJI. For pati
ents in group 2 (14 patients; 26 courses), doses (flows) were adapted
in a prospective study using the AJI software two to three times the f
irst day, then daily. They could have been adapted (retrospective stud
y) after platin pharmacokinetic parameters identification by APIS. The
dosage recommendations proposed by APIS the first day, from 12 hours
to 24 hours, to reach the target of 1.3 mg/L at 24 hours, and then dai
ly up to D4 (AAPT at Di) to maintain this level were compared to those
,which were really administered during the interactive treatment (DA a
t Di). There were no statistically significant difference for D2, D4 a
nd for the total dose (118.7 +/- 20.1 mg and 118.5 +/- 45.1 mg). The d
ifference war statistically significant for D1 and D3 (P < 0.05). The
inter-individual variability war less important with AJI (CV = 16.9% f
or DA total) than with APIS (CV = 38.0% for ADAPT total). The platin p
harmacokinetic parameters identified the first day by APIS were not st
atistically different from those identified from the whole treatment f
or clearance (5.92 and 5.63 l/d) and Vtotal 87.8 and 93.1 L); the diff
erence was statistically significant for Vinitial (34.7 and 42.5 L; P
< 0.05) and the terminal half-life (13.1 and 15.5 days; P < 0.05).