Should patients with ovarian cancer receive intraperitoneal chemotherapy following initial cytoreductive surgery?

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52 ■ CANCER WORLD ■ NOVEMBER-DECEMBER 2006
improvement in overall survival with
intraperitoneal cisplatin. Alberts et
al.2performed a direct head-to-head
comparison, whereas Markman et al.3
added two additional cycles of
high-dose carboplatin in the intraperi-
toneal arm. Although the prior studies
did not result in an NCI alert or a
change in clinical practice, the data in
aggregate warrant consideration of
first-line intraperitoneal therapy in
this group of patients. Before one
adopts the current regimen, several
issues deserve consideration.
GOG 172 compares three drugs
(two intraperitoneal and one intra-
venous) with two intravenously
administered drugs and a different
schedule. The intraperitoneal route
results in a continuous infusion via
the intraperitoneal and intravenous
route. Only 42% of the intraperi-
toneal arm received the assigned
intraperitoneal therapy, and 18% of
patients assigned to intraperitoneal
therapy received intravenous carbo-
platin and paclitaxel after discontinu-
ation of intraperitoneal therapy
because of toxicity. Toxicities result-
ing in discontinuation of the
intraperitoneal therapy included
problems related to the access
device, abdominal pain with infusion,
and intolerance to the higher doses of
cisplatin. How the number of cycles
of treatment affected survival is
unknown.
When GOG 172 was designed,
the results of GOG 158 were not
available. GOG 158 reported an
improvement in median overall sur-
vival of 8.7 months (relative risk 0.84;
95% CI 0.70–1.02) for patients treat-
ed with intravenous carboplatin and
paclitaxel compared with those treat-
ed with intravenous cisplatin and
paclitaxel.4Although cross-trial com-
parisons are not statistically valid and
the populations may differ, it is inter-
esting to compare the differences in
I
minimal residual disease following
initial cytoreductive surgery has been
rekindled with the recent publication
of a Gynecologic Oncology Group
study, GOG 172. This study com-
pared intravenous paclitaxel followed
by intraperitoneal cisplatin and pacli-
taxel, or by intravenous cisplatin, in
patients with stage III epithelial ovar-
ian cancer (optimal cytoreduction).
The authors reported a 15.9-month
improvement in median overall sur-
vival in those patients who received
intraperitoneal therapy. The National
Cancer Institute (NCI) issued a bul-
letin suggesting that, in women with
stage III epithelial ovarian cancer,
consideration should be given to the
administration of intraperitoneal cis-
platin and a taxane.1
This study and two previous ran-
domised trials demonstrated an
nterest in the intraperitoneal
delivery of chemotherapy to
patients with ovarian cancer with
*Carolyn Runowicz is Director of the Neag Comprehensive Cancer Center at the University of Connecticut Health Center, Farmington, Connecticut, USA
This article was first published in Nature Clinical Practice Oncology 2006 vol. 3 no. 8, and is reproduced with permission.
www.nature.com/clinicalpractice, doi:10.1038/ncponc0556, ©2006 Nature Publishing Group
➜Carolyn Runowicz*
Should patients with ovarian cancer
receive intraperitoneal chemotherapy
following initial cytoreductive surgery?
A novel intraperitoneal chemotherapy regimen, trialled in the GOG 172 study, represents a
new standard of care for patients with optimally resected stage III ovarian cancer, but should
be offered on an individualised basis.

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CANCER WORLD ■ NOVEMBER-DECEMBER 2006 ■ 53
outcome between the GOG 158
intravenous carboplatin plus pacli-
taxel arm and the GOG 172
intraperitoneal therapy arm. The dif-
ference in progression-free survival is
3.1 months and in overall survival 8.2
months between the two studies in
favour of the intraperitoneal route.
There are no differences in two-year
survival rates, and only a 4–5% differ-
ence in four-year survival rates.
The results of this study and the
previous phase III randomised tri-
als2,3suggest that a new standard of
care in chemotherapy has been
reached in the primary chemothera-
peutic management of small-volume
residual advanced ovarian cancer;
however, there remain a few hurdles
to widespread acceptance. Until
well-controlled, prospective ran-
domised trials demonstrate a survival
advantage over standard chemo-
therapy (intravenous carboplatin and
paclitaxel, instead of intravenous cis-
platin and paclitaxel, the control arm
in GOG 172), intraperitoneal therapy
need not be routinely administered to
patients with optimal stage III dis-
ease. What practitioners should not
do is make modifications to the regi-
men as published, as this might also
modify the treatment’s efficacy.
Details of the references cited in this article can be
accessed at www.cancerworld.org/cancerworld
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Synopsis
DK Armstrong, B Bundy, L Wenzel, et al. (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer.
N Engl J Med 354:34–43
Background. Surgery and standard intravenous chemotherapy with a platinum-taxane combination induces complete
remission in the majority of patients with newly diagnosed ovarian cancer. Most patients will eventually relapse and die from
their disease, however, despite escalation of the dose of intravenous chemotherapy. Although preclinical, clinical and phar-
macokinetic data support the use of intraperitoneal therapy in ovarian cancer, this strategy has not been widely accepted.
Objective. To explore whether the use of intraperitoneal chemotherapy with cisplatin and paclitaxel improves progres-
sion-free and overall survival compared with intravenous cisplatin and paclitaxel in ovarian cancer.
Design. In this randomised, phase III study conducted by the Gynecologic Oncology Group, patients with stage III epithe-
lial ovarian or peritoneal carcinoma who had not undergone previous chemotherapy or radiation were studied. Inclusion
criteria were Gynecologic Oncology Group performance status 0–2 (where 0 was fully active and 4 completely disabled),
residual mass following surgery limited to 1 cm in diameter, adequate hepatic and renal function, and normal blood counts.
Intervention. Between March 1998 and January 2001, participants were randomly assigned to receive six cycles of treat-
ment with intravenous paclitaxel (135 mg/m2) on day 1 followed by intravenous cisplatin (75 mg/m2) on day 2 (intravenous
therapy), or six cycles of intravenous paclitaxel (135 mg/m2) on day 1 followed by intraperitoneal cisplatin (100 mg/m2) on
day 2 and intraperitoneal paclitaxel (60 mg/m2) on day 8 (intraperitoneal therapy).
Outcome measures. Progression-free survival and overall survival were the primary endpoints, and toxicity and quality
of life were also assessed.
Results. Median progression-free survival was 18.3 months in the intravenous therapy group and 23.8 months in the
intraperitoneal therapy group (P=0.05). Median overall survival was 49.7 months in the intravenous therapy group and 65.6
months in the intraperitoneal therapy group (P=0.03). Compared with the intravenous therapy group, fewer patients in the
intraperitoneal therapy group received all six cycles of the assigned treatment (42% vs 83%), and more patients had severe
or life-threatening pain, fatigue or haematologic, metabolic, gastrointestinal, or neurologic toxicity (P<0.001). Catheter-
related complications comprised the main reason for discontinuation of intraperitoneal treatment. After adjustment for
baseline quality-of-life score, age and performance status, patients receiving intraperitoneal therapy had inferior quality of
life before cycle 4 (P<0.001) and 3-6 weeks after treatment compared with patients receiving intravenous therapy, but there
was no difference 1 year after treatment. Median duration of follow-up was 48.2 months in the intravenous therapy group
and 52.6 months in the intraperitoneal therapy group.
Conclusion. Women with optimally debulked ovarian cancer receiving intraperitoneal therapy with cisplatin and pacli-
taxel following intravenous therapy with paclitaxel had a substantial reduction in the risk of death compared with women
receiving intravenous paclitaxel plus cisplatin.
Acknowledgement: The synopsis was written by Petra Roberts, Associate Editor, Nature Clinical Practice