The use of pegylated liposomal doxorubicin with hyperthermic intraperitoneal chemotherapy(HIPEC) in patients undergoing cytoreductive surgery (CS) for peritoneal carcinomatosis ofovarian origin

Background: CS coupled with HIPEC is an attractive treatment option for patients with abdominalonly
malignancy. The present study examined the safety and pharmacokinetics of intraperitoneal
pegylated liposomal doxorubicin (PLD) used in the context of HIPEC in patients with peritoneal
carcinomatosis from ovarian carcinoma.
Patients and methods: Twenty-five patients with peritoneal carcinomatosis from ovarian carcinoma
underwent maximal CS followed by hyperthermic intraperitoneal perfusion with PLD (40 mg/m2)
for 60 min. PLD or free doxorubicin (DOX) levels were measured in perfusate and plasma from 14
patients, and in peritoneal or tumor samples from 4 and 2 patients, respectively.
RESULTS: Severe chemotherapy-related complications were not observed. The median
postoperative length of stay in the Hospital was 8 days (range, 5-21 days), two patients required
readmission within 30 days, and there were no operative mortalities. All patients were alive and free
of disease after a mean follow-up period of 18 months. During perfusion, the perfusate and plasma
contained PLD only at a perfusate:plasma ratio ≥300. Plasma PLD neither increased nor released
DOX over a 7 h post-perfusion period. Plasma PLD Cmax correlated negatively with the number of
surgery procedures. Peritoneal and tumor samples contained DOX only, which correlated positively
with PLD AUC in perfusate.
CONCLUSIONS: PLD was found to be an optimal drug for CS-HIPEC treatment of patients with
peritoneal carcinomatosis from ovarian carcinoma, with minimal systemic absorption or toxicity,
high activity coupled with DOX release in tumors. The peritoneum plays an active role in sitespecific
DOX release or systemic PLD absorption, according to a a modified three compartments
model.