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Annals of Surgical Oncology

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01-06-2013 | Colorectal Cancer

A Phase I Trial of Thermal Sensitization Using Induced Oxidative Stress in the Context of HIPEC

Authors: Lawrence E. Harrison, MD, Greg Tiesi, MD, Reza Razavi, PhD, Chia-Chi Wang, DO

Published in: Annals of Surgical Oncology | Issue 6/2013

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.

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Title: A Phase I Trial of Thermal Sensitization Using Induced Oxidative Stress in the Context of HIPEC
Authors: Lawrence E. Harrison, MD
Greg Tiesi, MD
Reza Razavi, PhD
Chia-Chi Wang, DO
Publication date: 01-06-2013
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 6/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-013-2874-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

A Phase I Trial of Thermal Sensitization Using Induced Oxidative Stress in the Context of HIPEC

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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