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TECHNIQUE OF INTRAPERITONEAL
CHEMOTHERAPY: NORMOTHERMIC AND
166HYPERTHERMIC
Asima Mukhopadhyay, MD, MRCOG, PhD, MSc
Introduction
Intraperitoneal (IP) chemotherapy in the field of
gynaecologic oncology has been targeted almost
exclusively at epithelial ovarian cancer (EOC), an
archetypal ‘peritoneal surface malignancy’ spreading
widely within the peritoneal cavity (PC), implanting on
all peritoneal surfaces but remaining confined by the
peritoneal lining for much of its natural history.
The theory and principles behind the delivery of IP
chemotherapy for peritoneal surface malignancies were
developed by Robert Dedrick and his colleagues at the
National Cancer Institute, USA and published in 1978
(1).
The temperature at which it is delivered can classify
IP chemotherapy: a) normothermic (37°C) and b)
hyperthermic (39-44°C). The former is usually given
on repeated occasions as a series of courses whilst the
latter is usually given as part of a treatment program that 10 years and survival improved with increasing number
includes a single HIPEC treatment at the time of surgery
followed by systemic chemotherapy.
Normothermic Intraperitoneal
Chemotherapy
Although there was considerable clinical research
interest into IP chemotherapy for EOC in the 1980s and
1990s, including two large randomized studies by the
Gynecologic Oncology Group (GOG) (2, 3) a surge in
interest appeared following the publication of a further
randomized study, GOG-172, in January 2006 (4). This
reported that patients randomized to receive combined
IP and intravenous (IV) chemotherapy had a median
survival of 65.6 months compared with 49.7 months
for patients receiving only IV chemotherapy. However,
the improved survival was achieved with considerable
toxicity and problems with the ports used for delivery
(5) resulting in only 40% of patients completing the
planned 6 courses of therapy. Nevertheless, National
Cancer Institute issued a clinical announcement advising
that all women with small volume disease remaining at
the completion of front-line surgery should at least be
offered IP chemotherapy.
C. William Helm, MB.BChir, FRCS
Subsequently, the use of IP chemotherapy has not
been universally adopted. In a prospective cohort study
of 823 women with stage III, optimally cytoreduced
ovarian cancer diagnosed between 2003-2012 at six
National Comprehensive Cancer Network institutions
in USA (6), adoption of IP/IV chemotherapy varied by
institution from 4% to 67% with only 43% of eligible
patients overall receiving modified IP/IV regimens at
treatment initiation. IP/IV chemotherapy was associated
with significantly improved 3 year overall survival (81%
v 71%; hazard ratio, 0.68; 95% CI, 0.47 to 0.99), compared
with IV chemotherapy, but also more frequent alterations
in the chemotherapy delivery route. Similar conclusions
were echoed in a retrospective analysis of data from GOG
114 and 172 with a median follow-up of 10.7 years (7);
the median survival with IP therapy was 61.8 months
compared with 51.4 months for IV therapy. IP therapy
was associated with a 23% decreased risk of death and
improved survival with gross residual (≤ 1 cm) disease.
The advantage of IP over IV therapy extended beyond
of IP cycles.
Current research needs include exploring methods of
reducing the complications of ports and the toxicity of
the chemotherapy by modifications in dose, drugs and
schedule. The emerging use of dose-dense paclitaxel,
anti-angiogenic and other novel therapies will make the
task of determining its role more difficult (8, 9). The
results of GOG-0252 (NCT00951496) will add further to
the debate.
Intraperitoneal Ports
A description of the technique of normothermic IP
chemotherapy can be divided into IP ports used to
deliver the chemotherapy and the delivery of the IP
chemotherapy itself.
History of IP Port Development
When Speyer and colleagues (10) first experimented with
IP chemotherapy delivery they used the catheter that
Tenckhoff and Schechter had developed for peritoneal
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