Phase I trial of pegylated liposomal doxorubicin with hyperthermic intraperitoneal chemotherapy in patients undergoing cytoreduction for advanced intra-abdominal malignancy

Lawrence E. Harrison, Margarette Bryan, Lilian Pliner, Tracie Saunders

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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/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. 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.

Original languageEnglish (US)
Pages (from-to)1407-1413
Number of pages7
JournalAnnals of Surgical Oncology
Volume15
Issue number5
DOIs
StatePublished - May 1 2008
Externally publishedYes

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Drug Therapy
Neoplasms
Patient Readmission
Anastomotic Leak
Survival
Maximum Tolerated Dose
Ileus
Wound Infection
liposomal doxorubicin
Postoperative Period
Doxorubicin
Disease-Free Survival
Length of Stay
Pharmacokinetics
Safety
Mortality
Serum
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

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title = "Phase I trial of pegylated liposomal doxorubicin with hyperthermic intraperitoneal chemotherapy in patients undergoing cytoreduction for advanced intra-abdominal malignancy",
abstract = "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/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. 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.",
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Phase I trial of pegylated liposomal doxorubicin with hyperthermic intraperitoneal chemotherapy in patients undergoing cytoreduction for advanced intra-abdominal malignancy. / Harrison, Lawrence E.; Bryan, Margarette; Pliner, Lilian; Saunders, Tracie.

In: Annals of Surgical Oncology, Vol. 15, No. 5, 01.05.2008, p. 1407-1413.

Research output: Contribution to journalArticle

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T1 - Phase I trial of pegylated liposomal doxorubicin with hyperthermic intraperitoneal chemotherapy in patients undergoing cytoreduction for advanced intra-abdominal malignancy

AU - Harrison, Lawrence E.

AU - Bryan, Margarette

AU - Pliner, Lilian

AU - Saunders, Tracie

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