High-pressure intrapleural chemotherapy: feasibility in the pig model.
BACKGROUND
The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model.


METHODS
Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure.


RESULTS
The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min.


CONCLUSIONS
High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura.
INSERM Unit 866, Equipe Avenir, Dijon, France. olivier.facy@chu-dijon.fr
Olivier
O
Facy
Pierre-Benoit
PB
Pages
Pablo
P
Ortega-Deballon
Guy
G
Magnin
Sylvain
S
Ladoire
Bernard
B
Royer
Bruno
B
Chauffert
Alain
A
Bernard
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011312:Pressure; D013552:Swine; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine