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

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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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Authors and Affiliations

  1. Division of Surgical Oncology, The Daniel and Gloria Blumenthal Cancer Center, The Valley Hospital, Paramus, NJ, USA

    Lawrence E. Harrison MD

  2. Department of Surgery, UMDNJ–New Jersey Medical School, Newark, NJ, USA

    Greg Tiesi MD, Reza Razavi PhD & Chia-Chi Wang DO

Authors
  1. Lawrence E. Harrison MD
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  2. Greg Tiesi MD
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  3. Reza Razavi PhD
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  4. Chia-Chi Wang DO
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Correspondence to Lawrence E. Harrison MD.

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Harrison, L.E., Tiesi, G., Razavi, R. et al. A Phase I Trial of Thermal Sensitization Using Induced Oxidative Stress in the Context of HIPEC. Ann Surg Oncol 20, 1843–1850 (2013). https://doi.org/10.1245/s10434-013-2874-0

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  • DOI: https://doi.org/10.1245/s10434-013-2874-0

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