A phase i trial of thermal sensitization using induced oxidative stress in the context of HIPEC

Lawrence E. Harrison, Greg Tiesi, Reza Razavi, Chia Chi Wang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Inducing oxidative stress under hyperthermic conditions significantly decreases tumor cell growth in a murine model of human colon cancer carcinomatosis. This phase I study examines the safety and pharmacokinetics of induced oxidative stress by the addition of hydrogen peroxide (H2O2) to the perfusate in patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced abdominal-only malignancies. Methods: Patients with advanced colon or appendiceal malignancies underwent maximal cytoreduction followed by HIPEC with mitomycin C (MMC). In addition, H2O2 was added to the perfusate at three concentrations (n = 3/level, 0.05, 0.075, 0.1 %). A control group consisted of patients perfused with MMC alone (n = 3). Perfusate, serum MMC, and H2O2 levels were measured, as were tissue levels of MMC. Results: Twelve patients were enrolled onto this trial. The median (range) peritoneal carcinomatosis index was 13 (3-20) requiring a median operative time of 6.3 (4-8.5) h. The median postoperative length of stay was 9 (5-34) days, with six patients requiring readmission within 30 days. Similar complications were observed at all three H2O2 levels, as well as in the control group. One patient required reexploration for a colon perforation (control group), and three patients developed enterocutaneous fistulas (0.075 % H2O2, 0.1 % H2O2 and control group). There were no operative mortalities. Conclusions: Hyperthermic intraperitoneal chemotherapy with induced oxidative stress after maximal cytoreduction is well tolerated. On the basis of the encouraging toxicity profile after cytoreduction and HIPEC with induced oxidative stress, a phase II trial to verify activity is indicated.

Original languageEnglish (US)
Pages (from-to)1843-1850
Number of pages8
JournalAnnals of Surgical Oncology
Volume20
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint

Oxidative Stress
Hot Temperature
Mitomycin
Drug Therapy
Control Groups
Colon
Intestinal Fistula
Carcinoma
Patient Readmission
Neoplasms
Operative Time
Colonic Neoplasms
Hydrogen Peroxide
Length of Stay
Pharmacokinetics
Safety
Mortality
Growth
Serum

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

@article{981f8d1bf13f43b6ae4f7842f3c4f331,
title = "A phase i trial of thermal sensitization using induced oxidative stress in the context of HIPEC",
abstract = "Background: Inducing oxidative stress under hyperthermic conditions significantly decreases tumor cell growth in a murine model of human colon cancer carcinomatosis. This phase I study examines the safety and pharmacokinetics of induced oxidative stress by the addition of hydrogen peroxide (H2O2) to the perfusate in patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced abdominal-only malignancies. Methods: Patients with advanced colon or appendiceal malignancies underwent maximal cytoreduction followed by HIPEC with mitomycin C (MMC). In addition, H2O2 was added to the perfusate at three concentrations (n = 3/level, 0.05, 0.075, 0.1 {\%}). A control group consisted of patients perfused with MMC alone (n = 3). Perfusate, serum MMC, and H2O2 levels were measured, as were tissue levels of MMC. Results: Twelve patients were enrolled onto this trial. The median (range) peritoneal carcinomatosis index was 13 (3-20) requiring a median operative time of 6.3 (4-8.5) h. The median postoperative length of stay was 9 (5-34) days, with six patients requiring readmission within 30 days. Similar complications were observed at all three H2O2 levels, as well as in the control group. One patient required reexploration for a colon perforation (control group), and three patients developed enterocutaneous fistulas (0.075 {\%} H2O2, 0.1 {\%} H2O2 and control group). There were no operative mortalities. Conclusions: Hyperthermic intraperitoneal chemotherapy with induced oxidative stress after maximal cytoreduction is well tolerated. On the basis of the encouraging toxicity profile after cytoreduction and HIPEC with induced oxidative stress, a phase II trial to verify activity is indicated.",
author = "Harrison, {Lawrence E.} and Greg Tiesi and Reza Razavi and Wang, {Chia Chi}",
year = "2013",
month = "6",
day = "1",
doi = "10.1245/s10434-013-2874-0",
language = "English (US)",
volume = "20",
pages = "1843--1850",
journal = "Annals of Surgical Oncology",
issn = "1068-9265",
publisher = "Springer New York",
number = "6",

}

A phase i trial of thermal sensitization using induced oxidative stress in the context of HIPEC. / Harrison, Lawrence E.; Tiesi, Greg; Razavi, Reza; Wang, Chia Chi.

In: Annals of Surgical Oncology, Vol. 20, No. 6, 01.06.2013, p. 1843-1850.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A phase i trial of thermal sensitization using induced oxidative stress in the context of HIPEC

AU - Harrison, Lawrence E.

AU - Tiesi, Greg

AU - Razavi, Reza

AU - Wang, Chia Chi

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Background: Inducing oxidative stress under hyperthermic conditions significantly decreases tumor cell growth in a murine model of human colon cancer carcinomatosis. This phase I study examines the safety and pharmacokinetics of induced oxidative stress by the addition of hydrogen peroxide (H2O2) to the perfusate in patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced abdominal-only malignancies. Methods: Patients with advanced colon or appendiceal malignancies underwent maximal cytoreduction followed by HIPEC with mitomycin C (MMC). In addition, H2O2 was added to the perfusate at three concentrations (n = 3/level, 0.05, 0.075, 0.1 %). A control group consisted of patients perfused with MMC alone (n = 3). Perfusate, serum MMC, and H2O2 levels were measured, as were tissue levels of MMC. Results: Twelve patients were enrolled onto this trial. The median (range) peritoneal carcinomatosis index was 13 (3-20) requiring a median operative time of 6.3 (4-8.5) h. The median postoperative length of stay was 9 (5-34) days, with six patients requiring readmission within 30 days. Similar complications were observed at all three H2O2 levels, as well as in the control group. One patient required reexploration for a colon perforation (control group), and three patients developed enterocutaneous fistulas (0.075 % H2O2, 0.1 % H2O2 and control group). There were no operative mortalities. Conclusions: Hyperthermic intraperitoneal chemotherapy with induced oxidative stress after maximal cytoreduction is well tolerated. On the basis of the encouraging toxicity profile after cytoreduction and HIPEC with induced oxidative stress, a phase II trial to verify activity is indicated.

AB - Background: Inducing oxidative stress under hyperthermic conditions significantly decreases tumor cell growth in a murine model of human colon cancer carcinomatosis. This phase I study examines the safety and pharmacokinetics of induced oxidative stress by the addition of hydrogen peroxide (H2O2) to the perfusate in patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced abdominal-only malignancies. Methods: Patients with advanced colon or appendiceal malignancies underwent maximal cytoreduction followed by HIPEC with mitomycin C (MMC). In addition, H2O2 was added to the perfusate at three concentrations (n = 3/level, 0.05, 0.075, 0.1 %). A control group consisted of patients perfused with MMC alone (n = 3). Perfusate, serum MMC, and H2O2 levels were measured, as were tissue levels of MMC. Results: Twelve patients were enrolled onto this trial. The median (range) peritoneal carcinomatosis index was 13 (3-20) requiring a median operative time of 6.3 (4-8.5) h. The median postoperative length of stay was 9 (5-34) days, with six patients requiring readmission within 30 days. Similar complications were observed at all three H2O2 levels, as well as in the control group. One patient required reexploration for a colon perforation (control group), and three patients developed enterocutaneous fistulas (0.075 % H2O2, 0.1 % H2O2 and control group). There were no operative mortalities. Conclusions: Hyperthermic intraperitoneal chemotherapy with induced oxidative stress after maximal cytoreduction is well tolerated. On the basis of the encouraging toxicity profile after cytoreduction and HIPEC with induced oxidative stress, a phase II trial to verify activity is indicated.

UR - http://www.scopus.com/inward/record.url?scp=84878241564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878241564&partnerID=8YFLogxK

U2 - 10.1245/s10434-013-2874-0

DO - 10.1245/s10434-013-2874-0

M3 - Article

C2 - 23354567

AN - SCOPUS:84878241564

VL - 20

SP - 1843

EP - 1850

JO - Annals of Surgical Oncology

JF - Annals of Surgical Oncology

SN - 1068-9265

IS - 6

ER -