Pharmacokinetics of cisplatin in semi-closed hyperthermic peritoneal perfusion (HPP) for treatment of peritoneal carcinomatosis.
BACKGROUND
This study investigates the pharmacokinetics and toxicity of cisplatin, admininistered by a new semi-closed hyperthermic peritoneal perfusion (HPP) technique to patients with peritoneal carcinomatosis.


METHODS
After surgical cytoreduction, 12 patients were given cisplatin 100 mg/m2 (CDDP), introduced into the HPP circuit for 60 min at 41.7 degrees C and 1200 ml/min flow rate. Perfusate and blood samples were obtained during/after perfusion, plus normal and tumor tissues samples before/after perfusion.


RESULTS
Total and ultrafiltrate (UF) CDDP had similar patterns: monophasic in peritoneum, biphasic in plasma. At the end of perfusion, total/UF platinum (Pt) concentrations in the peritoneum decreased by 63.4%-64.9%. Total/UF Pt concentrations and AUCtot in perfusate were higher than plasmatic ones. Pt concentrations in tumor specimens were higher than in normal tissues.


CONCLUSIONS
Cisplatin administered by semi-closed HPP evidenced pharmacological advantages: higher and direct drug exposure of the tumor within the peritoneal cavity, limited systemic absorption and mild toxicity.
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via Pietro Giuria 9, 10125 Torino, Italy. luigi.cattel@unito.it
Luigi
L
Cattel
Michele
M
De Simone
Roberto
R
Passera
Maria Cristina
MC
Verlengo
Laura
L
Delprino
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery / Q000628:therapy*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003131:Combined Modality Therapy; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects / Q000379:methods*; D007263:Infusions, Parenteral; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery / Q000628:therapy*; D010537:Peritoneum / Q000378:metabolism
D000970:Antineoplastic Agents; D002945:Cisplatin