Phase I trial of pegylated liposomal doxorubicin with hyperthermic intraperitoneal chemotherapy in patients undergoing cytoreduction for advanced intra-abdominal malignancy.
BACKGROUND
Cytoreduction coupled with hyperthermic intraperitoneal chemotherapy (HIPEC) is an attractive treatment option for a select group of patients with abdominal-only malignancy. The present phase I study examined the safety and pharmacokinetics of intraperitoneal pegylated liposomal doxorubicin (PLD) used in the context of HIPEC in patients with advanced abdominal-only malignancies.


METHODS
Patients with advanced abdominal malignancies underwent maximal cytoreduction and HIPEC with escalating doses of PLD (15-100 mg/m(2)). Perfusate, serum, and tissue doxorubicin levels were measured in five patients undergoing HIPEC at the maximum tolerated dose.


RESULTS
Twenty-one patients were enrolled in this trial. The maximum dose evaluated in this trial was 100 mg/m(2) and was well tolerated. The most common grade 3/4 complications were superficial wound infection and prolonged ileus. One patient developed an anastomotic leak in the postoperative period, requiring re-exploration. The median postoperative length of stay was 7 days (range, 4-29 days), three patients required readmissions within 30 days, and there were no operative mortalities The median follow-up time for was 13.7 months (range, 3-38 months). The median overall survival was 30.6 months with a median disease-free survival of 25 months.


CONCLUSIONS
We report that HIPEC with PLD following maximal cytoreduction in patients with advanced abdominal-only gastrointestinal or gynecologic malignancies is well tolerated. Encouraging survival after cytoreduction and HIPEC with PLD suggest that a phase II trial to verify activity is indicated.
D000328:Adult; D000368:Aged; D010478:Chemotherapy, Cancer, Regional Perfusion; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000556:secondary / Q000628:therapy*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012086:Reoperation; D015996:Survival Rate; D016896:Treatment Outcome
C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin