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1300 Technique of Intraperitoneal Chemotherapy: Normothermic and Hyperthermic
Table 5. Chemotherapy Agents With Activity prefer taxanes (paclitaxel/docetaxel) (36). The proposed
Enhanced by Hyperthermia That Can Be Given IP consensus of the ASPSM was for an inflow temperature of
42°C with a volume of 3 liters for 90 minutes. It is clear that
cisplatin irinotecan the HIPEC field is open for much more research and, as
with normothermic IP chemotherapy, it would be ideal if
carboplatin melphalan patients with EOC should receive this treatment modality
as participants in research protocols. Table 6 summarizes
oxaliplatin docetaxel the recently concluded, ongoing and new clinical trials
registered with clinicaltrials.gov. (40). It also reflects the
doxorubicin mitomycin heterogeneity of study designs, chemotherapy regimen
and dosage and endpoints. Of interest, a few studies
mitoxantrone vinorelbine have focused on translational endpoints (NCT02073500,
NCT02199171 and NCT02567253) as recent reports
Hyperthermic Intraperitoneal would indicate that HIPEC may have a beneficial role in
Chemotherapy platinum resistant disease too (26, 30-32). A systematic
review and meta-analysis showed a significantly better
The addition of moderate hyperthermia (39-44°C) has overall survival (OS) benefit of HIPEC when added to
been proposed as a means of enhancing the effects of IP CRS+ chemotherapy for both frontline and recurrent
chemotherapy in a technique called HIPEC (21). While epithelial ovarian cancers at 1 year (OR 3.76, 95% CI
cancer cells are susceptible to heat alone, hyperthermia 1.81-7.82) and continued through 5 year (OR 3.46,
also enhances the activity of many chemotherapy agents CI 2.19-5.48) and 8 years (OR 2.42, 95% CI 1.38-4.24)
in part by increasing cell uptake (Table 5) (22, 23). respectively. For overall disease free survival, carboplatin
was associated with an improved OS as compared to
Following the initial report of HIPEC for mitomycin or cisplatin (29).
pseudomyxoma peritonei in 1979 by Dr John Spratt, (24)
the first woman with EOC appears to have been treated Technique of HIPEC
in 1994 (25). Now more than 1500 cases of HIPEC in
ovarian cancers have been reported and subjected to Whatever the technique or timing of HIPEC it is essential
meta-analysis, with a single completed randomized trial to have a heat-exchange pump system that will heat the
(26) and many ongoing randomized controlled trials perfusate and circulate it throughout the PC.
(27-39).
A protocol should be in place for the handling of
There are theoretical reasons why HIPEC could chemotherapy agents in the operating room and recovery
reasonably be given at the time of surgery at several of areas and for management of toxic waste. A dedicated
the natural history time-points of EOC including at the team in the operating room is essential, including
time of front-line CRS, at CRS following neoadjuvant anesthesiologist, surgeon, pump technician and nursing
chemotherapy, for consolidation and at CRS for recurrent staff that will ensure efficient delivery with maximum
disease. HIPEC is generally given as a single treatment at safety for the patient and operating team (41, 42).
the time of surgery with the intent of treating microscopic
cancer cells disturbed by the surgery, so-called ‘floaters’, or HIPEC is performed under general anesthesia. The
microscopic or small volume macroscopic involvement patient is placed supine or in Allen stirrups according
of peritoneal surfaces. HIPEC may be repeated at the to procedure and surgeon preference. To monitor
time of second look surgery for consolidation and at the core body temperature a heat sensor is placed in the
time of surgery for recurrent disease. It would not usually esophagus and a urethral catheter with heat sensor probe
be considered as an isolated treatment but should always is placed in the bladder. The skin is prepared widely. A
be given in association with subsequent intravenous large sterile Ioban™-2 adhesive drape (3M Corp, St Paul,
chemotherapy. MN, USA) may be placed over the entire operative area
prior to draping to reduce the chance of chemotherapy
At the present time there are no proven ‘best’ drugs contamination. The CRS is then performed as necessary
or treatment modalities (temperature and duration to reduce peritoneal tumor volume to either no visible
of perfusion) for HIPEC. The American Society for disease or less than 5mm (29). Although the vaginal
Peritoneal Surface Malignancy (ASPSM) conducted vault must be closed prior to HIPEC many surgeons will
a survey of its members and others using HIPEC for leave reconstruction of bowel anastomoses until after.
EOC in an attempt to define current practice (Personal Approximately one hour before HIPEC will be given
Communication: Jesus Esquivel, MD). No formal the anesthiologist takes steps to lower the patient’s core
consensus has been reached but a proposed consensus temperature to 34-35°C, principally by lowering the air
included the use of carboplatin 800mg/m2 or cisplatin temperature in the room and switching off the warming
75mg/m2 for platinum sensitive disease and mitomycin blanket. The pump technician also starts to prepare the
40mg total dose (30mg initially and then 10mg at 45
minutes) for platinum resistant disease. Some groups
