Trial Information

Intra Peritoneal Chemo Hyperthermia (IPCH) : Cellular and Metabolic Consequences

Intra Peritoneal Chemo Hyperthermia (IPCH) is a recently validated option for the treatment
of peritoneal carcinomatosis from colorectal or ovarian origin. This therapeutic program
demonstrated a significant improvement of the late stages (i.e. carcinomatosis) of the
disease (survival median > 33 months). IPCH induces morbidity as high as 20% and mortality
less than 4%. From a clinical point of view, within the first 24 hours after IPCH, patients
undergo a systemic inflammatory response syndrome, and therefore require to be monitored in
an intensive care unit. From a metabolic perspective, preliminary data have been shown a
significant "anaerobic style" disturbance of energetic metabolism, suggesting a deep
cellular energetic deficit throughout IPCH process.

Putative contradictory effects of IPCH, like the increase of chemotherapy-related cellular
toxicity due to heat and on the other hand the initiation of a stress protein response
(heat shock response) which helps to reduce the cell injuries, leads to conduct a research
project on the underlying mechanisms: consequences, in terms of patient's care and
follow-up, are of high relevance.

Heat shock protein expression (stress protein response markers) and apoptosis are the main
chosen tools to evaluate IPCH-related cellular consequences.

Goals of the study Primary goal Multimodal assessment of the IPCH-related cell
modifications: signaling pathways, apoptosis and antitumoral immune response.

Secondary goal Comparative study of Heat shock protein expression, whether IPCH is done or
the patient is recused for the surgery due to intraoperative contraindication.

Method Prospective cohort follow up Procedure

Besides the usual care (surgical debulking and extensive tumoral resection after laparotomy
under general anesthesia), the research protocol includes :

- 7 blood samples over 72 hours (meaning less than 40 ml), including 4 samples under
general anesthesia throughout surgery and 3 samples during the 3 following days (at
24th, 48th and 72th hours).

- 6 tissue biopsies, i.e. 2 from peritoneum disease-free and 2 from invaded peritoneum ,
each representing a volume less than 1 cm3 and 2 biopsies from healthy colonic tissue
for the colon-related cancer and 4 biopsies (peritoneum n=2, tumoral tissue n=2) for
ovarian-related cancer. All biopsies are done during the surgery under general
anesthesia, and each biopsy per site before/after IPCH.

Assessment criteria

- main criteria : Heat shock protein expression (blood/cell ratio) compared to baseline
values.

- associate criteria : apoptosis and immune response before/after IPCH Statistical
method/Sample size/Study's lenght Scheduled sample size is 30 patients having an IPCH
and 30 patients contraindicated per surgery.

The normal distribution is verified using the d'Agostino-Pearson test. For intragroup
comparisons, the repeated measures ANOVA is done. For intergroup comparisons, an univariate
analysis is done, using the Student t-test and the Fisher exact test.

Taking into account the planned sample size and the annual number of IPCH, the scheduled
length of the study is 18 months.