Pharmacokinetics of intrapleural cisplatin for the treatment of malignant pleural effusions.
We determined the toxicity and pharmacokinetics of high-dose intrapleural cisplatin (CDDP) as a treatment of malignant pleural effusions (MPE). Fourteen patients with MPE were enrolled in this study. After complete drainage of the fluid, a catheter was inserted into the pleural cavity during a thoracoscopy. CDDP (300 mg) was administered via the catheter in a 6-h infusion. Peak levels, the areas under the concentration curve (AUC), and drug half-lives were measured in pleural fluid and plasma samples collected at 0 (baseline), 6, and 24 h as well as 4, 14, and 21 days after intrapleural administration. The dosage of CDDP ranged from 153 to 203 mg/m2. The time interval between infusion was prolonged until a maximum of 109 days. Only 7/40 infusions were associated with adverse effects in 4 patients (18%). Residual concentrations in pleural fluid (0.66+/-0.07 microgram /ml) were three-fold higher than in plasma (0.13+/-0.07 microgram/ml). In pleural fluid, maximal concentration (Cmax) varied from 19 to 900 microgram/ml and in plasma from 0.34 to 3.65 microgram/ml. AUC in plasma during the three courses was 112+/-49 microgram/ml/d. The T1/2 was 31+/-33 days higher than that previously reported after intravenous administration (8-15 days). Although intrapleural CDDP has the potential advantage of treating the underlying malignancy in addition to controlling the malignant effusion with a good tolerance, it cannot be recommended for the standard control of malignant pleural effusion. Indeed we observed a great variability of intrapleural CDDP concentration depending on the extent of pleural invasion and plasma diffusion. Further studies are needed to determine the value of high-dose intrapleural CDDP for the treatment of MPE.
Monjanel-Mouterde
S
S
Laboratory of pharmacokinetics, Hopital de la Timone, Marseille, France.
Frenay
C
C
Catalin
J
J
Boutin
C
C
Durand
A
A
Astoul
P
P
D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy*; D008875:Middle Aged; D010994:Pleura / Q000378:metabolism*; D010996:Pleural Effusion / Q000188:drug therapy*; D010997:Pleural Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D002945:Cisplatin