Phase I Trial of Pegylated Liposomal Doxorubicin with Hyperthermic Intraperitoneal Chemotherapy in Patients Undergoing Cytoreduction for Advanced Intra-abdominal Malignancy
- 256 Downloads
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.
Patients with advanced abdominal malignancies underwent maximal cytoreduction and HIPEC with escalating doses of PLD (15–100 mg/m2). Perfusate, serum, and tissue doxorubicin levels were measured in five patients undergoing HIPEC at the maximum tolerated dose.
Twenty-one patients were enrolled in this trial. The maximum dose evaluated in this trial was 100 mg/m2 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.
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.
KeywordsPhase I Doxorubicin Hyperthermia Cytoreduction Liposomal
- 1.Alexander HR BJ, Fraker DL. Rationale and clinical status of continuous hyperthermic peritoneal perfusion for the treatment of peritoneal carcinomatosis. In: DeVita VHS, Rosenberg S (ed.) Principles and Practices of Oncology Updates, Vol. 9. Philadelphia: JB Lippincott, 1995Google Scholar
- 14.Kummerle A, Krueger T, Dusmet M, et al. A validated assay for measuring doxorubicin in biological fluids and tissues in an isolated lung perfusion model: matrix effect and heparin interference strongly influence doxorubicin measurements. J Pharm Biomed Anal 2003;33:475–94PubMedCrossRefGoogle Scholar