National Medical Policy
Subject:
Intraperitoneal Chemotherapy for Ovarian
Cancer
Policy Number:
NMP339
Effective Date*:
May 2007
Update:
September 2015
This National Medical Policy is subject to the terms in the
IMPORTANT NOTICE
at the end of this document
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Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
1
Current Policy Statement
Health Net, Inc. considers intraperitoneal chemotherapy a medically necessary
treatment option for women with optimally debulked ovarian cancer (stage II and
III) who have undergone optimal surgical cytoreduction with no or minimal residual
(no tumor nodule < 1cm in diameter) disease.
Codes Related To This Policy
NOTE:
The codes listed in this policy are for reference purposes only. Listing of a code in
this policy does not imply that the service described by this code is a covered or noncovered health service. Coverage is determined by the benefit documents and
medical necessity criteria. This list of codes may not be all inclusive.
On October 1, 2015, the ICD-9 code sets used to report medical diagnoses and
inpatient procedures will be replaced by ICD-10 code sets. Health Net National
Medical Policies will now include the preliminary ICD-10 codes in preparation for this
transition. Please note that these may not be the final versions of the codes and
that will not be accepted for billing or payment purposes until the October 1, 2015
implementation date.
ICD-9 Codes
183.0 – 183.9
Malignant neoplasm of ovary and other uterine adnexa
ICD-10 Codes
C56.1-C56.9
Malignant neoplasm of ovary
CPT Codes
96446
Chemotherapy administration into peritoneal cavity via
indwelling port or catheter
HCPCS Codes
J9060
J9265
Cisplatin, powder or solution, per 10 mg
Injection, Paclitaxel, 30 mg
2015 HCPCS Codes
J9267
Injection, paclitaxel, 1 mg
Scientific Rationale – Update September 2015
Tewari et al. (2015) completed a study to determine long-term survival and
associated prognostic factors after intraperitoneal (IP) chemotherapy in patients with
advanced ovarian cancer. Data from Gynecologic Oncology Group protocols 114 and
172 were retrospectively analyzed. Cox proportional hazards regression models were
used for statistical analyses. In 876 patients, median follow-up was 10.7 years.
Median survival with IP therapy was 61.8 months (95% CI, 55.5 to 69.5), compared
with 51.4 months (95% CI, 46.0 to 58.2) for intravenous therapy. IP therapy was
associated with a 23% decreased risk of death (adjusted hazard ratio [AHR], 0.77;
95% CI, 0.65 to 0.90; P = .002). IP therapy improved survival of those with gross
residual (≤ 1 cm) disease (AHR, 0.75; 95% CI, 0.62 to 0.92; P = .006). Risk of
death decreased by 12% for each cycle of IP chemotherapy completed (AHR, 0.88;
95% CI, 0.83 to 0.94; P < .001). Factors associated with poorer survival included:
clear/mucinous versus serous histology (AHR, 2.79; 95% CI, 1.83 to 4.24; P <
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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.001), gross residual versus no visible disease (AHR, 1.89; 95% CI, 1.48 to 2.43; P
< .001), and fewer versus more cycles of IP chemotherapy (AHR, 0.88; 95% CI,
0.83 to 0.94; P < .001). Younger patients were more likely to complete the IP
regimen, with a 5% decrease in probability of completion with each year of age
(odds ratio, 0.95; 95% CI, 0.93 to 0.96; P < .001). The advantage of IP over
intravenous chemotherapy extends beyond 10 years. IP therapy enhanced survival
of those with gross residual disease. Survival improved with increasing number of IP
cycles.
Scientific Rationale – Update September 2014
Per NCCN guidelines (3.2014) on Ovarian cancer, “Patients with low-volume residual
disease after surgical cytoreduction for invasive epithelial ovarian or peritoneal
cancer are potential candidates for intraperitoneal (IP) therapy. In these patients,
consideration should be given to placement of IP catheter with initlal surgery. The
guidelines note, “The intravenous/IP chemotherapyregimine (IP chemotherapy) is
recommended for stage III patients with optimally debulked (<1cm residual) disease
based on randomized controlled trials (category 1). Stage II patients may also
receive IP chemotherapy, although no randomized evidence for stage II has been
published.”
Suidan et al (2014) compared survival outcomes for patients with advanced
epithelial ovarian cancer (EOC) who received primary intravenous/intraperitoneal
(IV/IP) chemotherapy to those who received IV followed by consolidation (treatment
given to patients in remission) IP chemotherapy. Data was analyzed and compared
for all patients with stage III-IV EOC who underwent optimal primary cytoreduction
(residual disease ≤1cm) followed by cisplatin-based consolidation IP chemotherapy
(1/2001-12/2005) or primary IV/IP chemotherapy (1/2005-7/2011). The authors
identified 224 patients; 62 (28%) received IV followed by consolidation IP
chemotherapy and 162 (72%) received primary IV/IP chemotherapy. The primary IP
group had significantly more patients with serous tumors. The consolidation IP group
had a significantly greater median preoperative platelet count, CA-125, and amount
of ascites. There were no differences in residual disease at the end of cytoreduction
between both groups. The median progression-free survival (PFS) was greater for
the primary IP group; however, this did not reach statistical significance
(23.7months vs 19.7months; HR 0.78; 95% CI, 0.57-1.06; p=0.11). The median
overall survival (OS) was significantly greater for the primary IP group (78.8months
vs 57.5months; HR 0.56; 95% CI, 0.38-0.83; p=0.004). On multivariate analysis,
after adjusting for confounders, the difference in PFS was not significant (HR 0.78;
95% CI, 0.56-1.11; p=0.17), while the difference in OS remained significant (HR
0.59; 95% CI, 0.39-0.89; p=0.01). The authors concluded in this study, primary
IV/IP chemotherapy was associated with improved OS compared to IV followed by
consolidation IP chemotherapy in patients with optimally cytoreduced advanced EOC.
Barrios et al (2014) conducted a pilot study to investigate a regimen of combination
IP carboplatin and IV and IP paclitaxel. A prospectively maintained database was
used to identify all patients who received IP and IV chemotherapy after an optimal
cytoreductive surgery for advanced epithelial ovarian carcinoma from May 2007 to
June 2013. The regimen consisted of day 1 administration of IP carboplatin AUC 6
and IV paclitaxel 175 mg/m over 3 hours and day 8 IP paclitaxel 60 mg/m over 1
hour. Common toxicity criteria for adverse events were used to classify toxicities.
Protocol toxicities and oncologic outcomes were recorded. Twenty patients received
the treatment protocol. The median age was 62 years (range 42-88 years). The
median CA-125 at presentation was 296 units/mL (range 31-4,838 units/mL).
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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Nineteen (95%) patients were stage IIIC. The median number of IP cycles completed
was six (range five to six cycles). Grade 3 and 4 toxicities occurred in 11 (55%) and
10 (50%) patients, respectively. The following grade 3 and 4 toxicities occurred:
neutropenia in 14 (70%) patients, thrombocytopenia in five (25%), anemia in four
(20%), nausea in two (10%), and fatigue in one (5%). With a median follow-up of
20 months, the median progression-free survival has not yet been met. The 5-year
overall survival rate was 80%. Investigators concluded combination day 1 IP
carboplatin, IV paclitaxel, and day 8 IP paclitaxel after optimal cytoreductive surgery
for advanced-stage epithelial ovarian cancer is effective and safe.
Bowles et al (2014) reported a 2006 National Cancer Institute clinical announcement
recommended the use of IV and IP chemotherapy over IV chemotherapy alone for
women with International Federation of Gynecology and Obstetrics (FIGO) stage 3
optimally debulked ovarian cancer due to significant survival benefit demonstrated in
multiple randomized clinical trials. The authors examined uptake of IP chemotherapy
in community practice before and after this recommendation. They identified 288
women with FIGO stage 2 or greater incident ovarian cancer diagnosed from 2003 to
2008 at three integrated delivery systems in the US. Administrative health plan data
were used to determine patient characteristics and receipt of IV and IP
chemotherapy within 12 months of diagnosis. We compared characteristics of women
receiving IV chemotherapy alone vs. IP chemotherapy (with or without IV
chemotherapy) and assessed temporal trends in IP chemotherapy use. Overall
12.5% (n=36) of women received IP chemotherapy during the study period. IP
chemotherapy use was non-existent between 2003 and 2005. Use of IP
chemotherapy occurred among 26.9% of women diagnosed in 2006 and plateaued at
20.4% of women diagnosed in 2008. IP recipients were younger (mean age 55.9 vs.
63.5years, p=<0.001) and more likely to have stage 3 ovarian cancer (77.8 vs.
50.4% p=0.039) compared to their IV-only chemotherapy counterparts. The
authors concluded use of IP chemotherapy for newly diagnosed advanced stage
ovarian cancer patients was uncommon in this community setting. Future research
should identify potential patient, physician, and system barriers and facilitators to
using IP chemotherapy in this setting.
Robinson and Cantillo ( 2014) compared the rate of completion of optimal debulking
and/or 6 cycles of IP chemotherapy in women with International Federation of
Gynecologists and Obstetricians stage III/IV ovarian cancer undergoing neoadjuvant
chemotherapy (NACT) versus primary surgery (PS) and to compare morbidity
between these 2 groups. Ninety-six subjects with stage III/IV ovarian cancer who
underwent either NACT or PS were identified. Data comparisons include rate of
optimal debulking and completion rate of 6 cycles of IP chemotherapy. Other data
collected included surgical times, length of stay, intensive care unit admissions,
blood transfusions, bowel resections, major complications, and dose reductions.
SigmaStat version 2.0 was used for statistical analysis. Of the 96 subjects, 38
received NACT and 58 had PS. All 14 subjects with stage IV disease received NACT,
and all experienced resolution of pleural effusion, based on computed tomographic
imaging. Thirty-five (92%) of 38 NACT subjects versus 47 (81%) of 58 PS subjects
were optimally debulked (P = 0.08). Thirty-six (95%) of 38 NACT subjects versus 37
(64%) of 58 PS subjects completed IP chemotherapy (P < 0.001). Length of stay
was 3.26 (NACT) versus 5.08 (PS) days (P < 0.001). Intensive care unit admissions
were 1 of 38 (NACT) versus 12 of 58 (PS) (P < 0.001). Bowel resections were done
in 2 of 38 (NACT) versus 14 of 38 (PS) (P < 0.05). Duration of surgery was 96
minutes (NACT) versus 138 minutes (PS) (P < 0.001). A trend to fewer dose
reductions occurred in NACT (1/38) versus PS (8/58) (P = 0.056). Investigators
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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concluded the NACT subjects were more likely to complete IP chemotherapy and had
decreased length of stay, intensive care unit admissions, bowel resections, and
duration of surgery. Both optimal debulking and dose reductions were numerically
but not statistically associated with NACT versus PS. This likely reflects a relatively
high overall rate of optimal debulking and low rate of dose reductions in these
subjects and would require a larger group to determine significance.
Blinman et al (2013) sought to determine the regimen's feasibility, adverse events,
catheter-related complications, progression-free survival, health-related quality of
life (HRQL), and patients' preferences for IP versus IV chemotherapy. The authors
conducted a single arm, multi-center study of IP chemotherapy with IV paclitaxel
135 mg/m(2) (D1) over 3 hours, IP cisplatin 75 mg/m(2) (D2), and IP paclitaxel 60
mg/m(2) (D8) for 6 cycles in women with optimally debulked stage III ovarian or
related cancers. Thirty-eight eligible patients were recruited from 12 sites between
July 2007 and December 2009. Seventy-one percent (n=27) completed at least 4
cycles and 63% (n=24) completed all 6 cycles. Grade 3 or 4 adverse events included
nausea (n=2), vomiting (n=2), abdominal pain (n=2), and diarrhea (n=1), but not
febrile neutropenia, neurotoxicity, or nephropathy. There were no treatment-related
deaths. Catheter-related complications were the most frequent cause of early
discontinuation of treatment (16 patients, 21%). Apart from neurotoxicity HRQL
which worsened over time, HRQL was stable or improved with time. Most patients
(≥50%) judged moderate benefits (e.g., an extra 6 months survival time or a 5%
improvement in survival rates) necessary to make IP chemotherapy worthwhile. The
authors concluded IP chemotherapy was feasible, tolerable, and most participants
considered moderate survival benefits sufficient to warrant the adverse effects and
inconvenience.
Scientific Rationale – Update September 2013
Barlin et al. (2012) completed the Gynecologic Oncology Group (GOG) study 172,
which demonstrated improved progression-free (PFS) and overall (OS) survival for
patients with stage III optimally debulked ovarian and peritoneal carcinoma treated
with IV/IP paclitaxel and intraperitoneal (IP) cisplatin compared to standard IV
therapy. The inpatient administration, toxicity profile, and limited completion rate
have been blamed for the lack of acceptance and widespread use of this regimen.
The authors sought to evaluate the PFS, OS, toxicity, and completion rate of a
modified outpatient IP regimen. Using a prospectively maintained database, the
authors evaluated the outcomes of patients who underwent primary optimal
cytoreduction for stage III ovarian, tubal, or peritoneal carcinoma followed by IV/IP
chemotherapy from 1/05-3/09. Our modified regimen was as follows: IV paclitaxel
(135 mg/m(2)) over 3h on day 1, IP cisplatin (75 mg/m(2)) on day 2, and IP
paclitaxel (60 mg/m(2)) on day 8, given every 21 days for 6 cycles. The authors
identified 102 patients who initiated the modified IV/IP regimen and completed
chemotherapy. The median follow-up was 43 months. The median age at diagnosis
was 57 years (range, 23-76). Primary disease site was: ovary, 77 (75%); fallopian
tube, 13 (13%); peritoneum, 12 (12%). FIGO stage was: IIIA, 8 (8%); IIIB, 4
(4%); IIIC, 90 (88%). Residual disease after cytoreduction was: none, 58 (57%); ≤
1 cm, 44 (43%). The most frequent grade 3/4 toxicities were: neutropenia, 12
(12%); gastrointestinal, 8 (8%); neurologic, 6 (6%). Eighty-two (80%) of 102
patients completed 4 or more cycles of IV/IP therapy; 56 (55%) completed all 6
cycles. The median PFS and OS were 29 and 67 months, respectively. By modifying
the GOG 172 treatment regimen, convenience, toxicity, and tolerability appear
improved, with survival outcomes similar to those of GOG 172. This modified IV/IP
regimen warrants further study.
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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The 2013 National Comprehensive Cancer Network (NCCN) guidelines on ovarian
cancer states intraperitoneal (IP) chemotherapy notes intraperitoneal (IP)
chemotherapy in <1cm optimally debulked Stage II patients and Stage III patients,
(i.e., Category I for Stage III, based on randomized controlled trials). Stage II
patients are based on a NCCN 2A category recommendation, which is now
considered medically necessary, and has been added to the policy statement. (Note:
2A recommendation is based upon lower level evidence but there is uniform NCCN
consensus that the intervention is appropriate).
Scientific Rationale – Update August 2012
The 2012 National Comprehensive Cancer Network (NCCN) guidelines on ovarian
cancer states intraperitoneal (IP) chemotherapy notes intraperitoneal (IP)
chemotherapy in <1cm optimally debulked Stage II patients and Stage III patients
(Category I for Stage III, based on randomized controlled trials). NCCN further notes
that “ Patients with low volume disease after surgical cytoreduction for invasive
epithelial ovarian or peritoneal cancer are potential candidates for intraperitoneal
(IP) therapy. In these patients care should be given to placement of IP catheter with
initial surgery”. There continues to be a paucity of randomized controlled trials for
Stage II patients.
Scientific Rationale – Update September 2011
The 2011 National Comprehensive Cancer Network (NCCN) guidelines on ovarian
cancer states intraperitoneal (IP) chemotherapy is recommended in Stage III
patients with optimally debulked <1cm residual disease, based on randomized
controlled trials, noted below in initial scientific rationale. (Category I for stage III).
They also note in the guidelines stage II patients may also receive IP chemotherapy,
although no randomized evidence for stage II have been published.
Clinical Trials are ongoing evaluating both intraperitoneal chemotherapy and
hyperthermic intraperitoneal chemotherapy for ovarian cancer.
Scientific Rationale Update – December 2010
The 2011 National Cancer Comprehensive Network (NCCN) guidelines on ovarian
cancer state:


Intraperitoneal (IP) chemotherapy is recommended in Stage III patients with
optimally debulked <1cm residual disease, based on randomized controlled
trials, noted below in initial scientific rationale. (Category I for stage III).
Patients with low volume residual disease after surgical cytoreduction for
invasive epithelial ovarian or peritoneal cancer are potential candidates for
intraperitoneal therapy. In these patients, consideration should be given to
placement of IP catheter with initial surgery.
Tierstan et al. (2009) completed a phase II evaluation of neoadjuvant chemotherapy
and debulking followed by intraperitoneal chemotherapy in women with stage III and
IV epithelial ovarian, fallopian tube or primary peritoneal cancer. Women with
adenocarcinoma by biopsy or cytology with stage III/IV (pleural effusions only)
epithelial ovarian, fallopian tube or primary peritoneal carcinoma that presented with
bulky disease were treated with neoadjuvant intravenous (IV) paclitaxel 175 mg/m2
and carboplatin AUC 6 q 21 daysx3 cycles followed by surgery (if >/=50% decrease
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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in CA125). If optimally debulked they received IV paclitaxel 175 mg/m2 and IP
carboplatin AUC 5 (day 1) and IP paclitaxel 60 mg/m2 (day 8) q 28 daysx6 cycles.
Sixty-two patients were registered. Four were ineligible. Fifty-six were evaluated for
neoadjuvant chemotherapy toxicities. One patient died of pneumonia. Five patients
had grade 4 toxicity, including neutropenia (3), anemia, leukopenia, anorexia,
fatigue, muscle weakness, respiratory infection, and cardiac ischemia. Thirty-six
patients had debulking surgery. Two had grade 4 hemorrhage. Twenty-six patients
received post-cytoreduction chemotherapy. Four had grade 4 neutropenia. At a
median follow-up of 21 months, median PFS is 21 months and median OS is 32
months for all 58 patients. PFS and OS for the 26 patients who received IV/IP
chemotherapy is 29 and 34 months respectively. These results compare favorably
with other studies of sub-optimally debulked patients.
Ziemet et al. (2009) Development of the pros and cons of intraperitoneal (IP)
chemotherapy in the treatment of epithelial ovarian cancer based on the most
prominent data published on the evolution of IP chemotherapy and on experience
with this therapeutic strategy in clinical routine. The literature published on IP
chemotherapy in ovarian cancer between 1970 and 2008 was identified
systematically by computer-based searches in MEDLINE and the Cochrane Library.
Furthermore, a preliminary analysis of data recorded during an observational
nationwide multicenter study of the Austrian AGO on IP-IV chemotherapy using the
GOG-172 treatment regimen was performed. The literature review unequivocally
revealed a significantly greater toxicity for IP than for intravenous (IV) cisplatinbased chemotherapy. However, according to a Cochrane meta-analysis, IP-IV
administration of chemotherapy is associated with a 21.6% decrease in the risk for
death. In agreement with earlier reports, the most frequently mentioned side-effects
in the Austria-wide observational study were long-lasting neurotoxicity, abdominal
pain, fatigue, gastrointestinal and metabolic toxicities, and catheter-related
complications. Most of these toxicities were identified as mirroring the toxicity profile
of high-dose IV cisplatin (>or=100 mg/m(2)). In some patients, the classic IP-IV
regimen with cisplatin/paclitaxel was changed to an alternative schedule comprising
carboplatin AUC 5 (d1) and weekly paclitaxel 60 mg/m(2) (d1, 8, 15) completely
administered via the IP route. This treatment was better tolerated and quality of life
was significantly less compromised. However, neutropenia and thrombocytopenia
were the limiting side-effects of this IP regimen. In cases where optimal
cytoreduction with residual disease <or=1 cm was achieved during primary surgery
and disease was confined to the peritoneal cavity, IP chemotherapy should be given
serious consideration, even at the expense of significantly increased, but
manageable toxicity.
Scientific Rationale Initial
There is a growing body of evidence showing a survival advantage for intraperitoneal
(IP) cisplatin as compared to IV administration of platinum along with intravenous
taxane-based chemotherapy in women with optimally cytoreduced stage III epithelial
ovarian cancer. The publication of results from the most recent of these trials,
Gynecologic Oncology Group (GOG) trial 172, led the US National Cancer Institute to
issue a Clinical Alert, strongly encouraging the use of IP chemotherapy in this subset
of patients.
On January 5, 2006, the National Cancer Institute (NCI) released a clinical
announcement concerning recommended treatment for advanced ovarian cancer.
Based on the results of eight phase III clinical trials, the NCI is encouraging doctors
to follow surgery with a combination of two drug-delivery methods: intravenous and
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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intraperitoneal. The combined approach, though more toxic, extends overall survival
for women with advanced ovarian cancer by about a year compared to intravenous
delivery alone. Patients should be provided with information on the survival and
toxicity for both IP chemotherapy and intravenous therapies, as well as practical
information about the administration of each regimen, so that they may play an
active role in the decision-making process.
The Society of Gynecologic Oncologists (SGO) issued a position statement to
comment on the NCI Clinical Announcement regarding the use of intraperitoneal (IP)
chemotherapy in ovarian cancer. The policy statement notes the following:
“Intraperitoneal chemotherapy should only be considered in women who
have undergone optimal cytoreductive surgery with residual tumor nodules
less than 1 cm in diameter - microscopic or near microscopic disease is most
desirable. In this regard, studies have shown that gynecologic oncologists
are more likely to perform optimal debulking of ovarian cancer than other
surgeons. The NCI recommendation that IP chemotherapy be considered
only for patients who are optimally debulked further highlights the
importance of referral of women with known or suspected ovarian cancer to
a gynecologic oncologist or other physician with special expertise and
training in ovarian cancer cytoreductive surgery.
Although there is good evidence that IP chemotherapy increases median
survival, it remains unclear whether this translates into higher cure rates. In
addition, there is presently no consensus regarding what constitutes the
“standard” IP chemotherapy regimen. Furthermore, the intensity and toxicity
of IP chemotherapy generally is higher than that of IV chemotherapy and IP
chemotherapy may be poorly tolerated by patients who do not have an
excellent performance status. In view of these issues, the decision whether
or not to use IP chemotherapy should be decided on a case-by-case basis by
each patient and her physician.
The issues and challenges associated with the administration of IP
chemotherapy differ from those encountered with IV chemotherapy. Most
notably, this includes surgical insertion and maintenance of IP catheters as
well as management of complications, such as catheter obstruction, infection
and bowel fistula. In view of this, IP chemotherapy should be given by
oncologists who have appropriate expertise and experience with this
approach.”
Epithelial ovarian cancers can spread by local extension, by intra-abdominal
dissemination to other sites within the peritoneal cavity, and by lymphatic spread to
pelvic and para-aortic nodes in the retroperitoneum. The most common route of
ovarian cancer spread is within the peritoneal cavity. Intraperitoneal (IP)
administration of chemotherapy was first proposed several decades ago. Certain
chemotherapeutic agents, including cisplatin and, more recently, paclitaxel, were
found to have distinct pharmacokinetic advantages when given via an intraperitoneal
route. These include high intraperitoneal concentration of drug, as well as a longer
half-life of the drug in the peritoneal cavity, compared to that observed with
intravenous (IV) administration. For cisplatin there was a 10-20-fold greater
exposure in the peritoneal cavity over what is achieved with the IV route. In
addition, the intraperitoneal administration resulted in prolonged systemic exposure
to the chemotherapeutic agents. The penetration into tumor tissue is limited to a few
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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millimeters of tumor on the peritoneal surface layers, therefore, this approach is best
suited to patients with minimal residual disease after surgical cytoreduction.
The optimal timing of IP catheter/port placement has not been established. The IP
access device can be placed at the time of laparotomy performed for initial diagnosis,
staging, and cytoreduction or it could be placed laparoscopically or by minilaparotomy in the post operative period. The drug delivery device should be a fully
implantable port attached to a single lumen venous silicone catheter of large size so
that it does not kink and obstruct flow. The catheter is only needed for infusion, and
withdrawal of fluid is not needed after chemotherapy. While there have been no
studies comparing different IP chemotherapy port locations, the most commonly
recommended site is two to three fingerbreadths above the right or left costal margin
in the midclavicular line. This location permits the port reservoir to be trapped
against a fixed underlying structure while it is being accessed. This prevents internal
rotation of the reservoir, and difficulty with insertion of the Huber needle into the
port, which can be a problem if the device is placed in the right or left lower
quadrant. Contraindications to IP port placement include patients at poor surgical
risk, active peritonitis or sepsis, and the presence of extensive intraabdominal
adhesions, because they prevent adequate distribution of instilled chemotherapeutic
agents. In addition, patients who had removal of a portion of the left side of the
colon during surgery may have more difficulty with IP therapy. IP chemotherapy
may be discontinued prematurely due to abdominal pain with infusions, intolerance
to the higher dose cisplatin and problems related to the access device.
The GOG conducted a randomized, phase III trial (Armstrong et al., 2006) that
compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus
intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer. 415
patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no
residual mass greater than 1.0 cm were randomized to receive 135 mg of
intravenous paclitaxel per square meter of body-surface area over a 24-hour period
followed by either 75 mg of intravenous cisplatin per square meter on day 2
(intravenous-therapy group) or 100 mg of intraperitoneal cisplatin per square meter
on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8
(intraperitoneal-therapy group). Treatment was given every three weeks for six
cycles. Quality of life was assessed. Grade 3 and 4 pain, fatigue, and hematologic,
gastrointestinal, metabolic, and neurologic toxic effects were more common in the
intraperitoneal-therapy group than in the intravenous-therapy group. Only 42
percent of the patients in the intraperitoneal-therapy group completed six cycles of
the assigned therapy, but the median duration of progression-free survival in the
intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months,
respectively. The median duration of overall survival in the intravenous-therapy and
intraperitoneal-therapy groups was 49.7 and 65.6 months, respectively. Quality of
life was significantly worse in the intraperitoneal-therapy group before cycle 4 and
three to six weeks after treatment but not one year after treatment. The
investigators concluded as compared with intravenous paclitaxel plus cisplatin,
intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival
in patients with optimally debulked stage III ovarian cancer.
Elit et al. (2007) performed a systematic review with meta-analyses of published
randomized trials that compared first-line intraperitoneal-containing chemotherapy
with first-line intravenous chemotherapy in the treatment of women with stage III
epithelial ovarian cancer. Seven randomized, controlled trials were identified,
including 3 large Phase III trials and 4 smaller randomized trials. The 3 large Phase
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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III trials detected statistically significant overall survival benefits with intraperitoneal
cisplatin-containing chemotherapy compared with intravenous chemotherapy alone.
Pooled analysis from 6 of the 7 randomized trials confirmed the survival effect with
intraperitoneal chemotherapy compared with intravenous chemotherapy alone.
Severe adverse events and catheter-related complications with intraperitoneal
chemotherapy were significantly more common and often were dose-limiting. The
reviewer concluded that the results from this review indicated that cisplatincontaining intraperitoneal chemotherapy should be offered to patients on the basis of
significant improvements in overall survival. The appropriate clinical and institutional
multidisciplinary facilities are needed for the safe delivery of this treatment in
optimally debulked patients. The investigator also noted that further research is
needed concerning specific aspects of the treatment, such as optimal agent, dose,
and scheduling.
Fung-Kee-Fung et al. (2007) also performed a review of the available evidence on IP
chemotherapy for patients with advanced ovarian cancer. Eight randomized trials
comparing IP chemotherapy versus intravenous (IV) chemotherapy were identified.
Three trials reported statistically significant improvements in median survival of 8.0,
11.0, and 15.9 months with cisplatin-based IP chemotherapy. In one trial, the 15.9month improvement in median overall survival (RR=0.75, 95% CI=0.58-0.97)
represented a 25% reduction in the risk of death with IP chemotherapy. Severe
adverse events and catheter-related complications were often dose limiting with IP
chemotherapy. The reviewer concluded that survival benefits with cisplatin-based IP
chemotherapy may represent a significant improvement in the outlook for select
patients with advanced ovarian cancer. The delivery of IP chemotherapy is more
challenging than the IV route; however, severe adverse events and catheter-related
complications may be offset through research defining the optimum treatment
regimen, and the standardization of care. He noted further that system-wide
standards for the delivery of IP chemotherapy for patients with optimally debulked
stage III ovarian cancer are offered in Canada.
Improved outcomes with IP chemotherapy was confirmed in a Cochrane metaanalysis (2006). The reviewer found that overall survival and progression free
survival from advanced ovarian cancer was increased with IP chemotherapy. The
reviewers retrieved data on overall and disease free survival as well as adverse
events and QOL and then performed a meta-analysis of outcomes, using hazard
ratios for time-to-event variables and relative risks for dichotomous outcomes. Eight
randomised trials studied 1819 women receiving primary treatment for ovarian
cancer. Women were less likely to die if they received an intraperitoneal (IP)
component to the chemotherapy (hazard ratio (HR) =0.79; 95% confidence interval
(CI): 0.70 to 0.90) and the disease free interval (HR =0.79; 95%CI: 0.69 to 0.90)
was also significantly prolonged. The reviewers noted that there might be greater
serious toxicity with regard to gastrointestinal effects, pain and fever but less
ototoxicity with the intraperitoneal than the intravenous route. The reviewer
concluded that the results of the meta-analysis provide the most reliable estimates
of the relative survival benefits of IP over IV therapy. It was noted, however, that
the potential for catheter related complications and toxicity needs to be considered
when deciding on the most appropriate treatment for each individual woman. The
reviewer noted further that the optimal dose, timing and mechanism of
administration could not be addressed from this meta-analysis and would need to be
addressed in the next phase of clinical trials.
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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Ovarian cancer is the fifth most common cause of cancer-related death in females in
the United States and the most common cause of death among women who develop
gynecologic cancer. The majority of primary ovarian tumors derive from epithelial
cells (epithelial carcinoma) while the remainder arise from germ cell tumors, sex
cord-stromal tumors, and mixed cell tumors. The incidence of ovarian cancer
increases with age; the mean age of diagnosis in the mid-fifties. Risk factors in the
etiology of ovarian cancer include nulliparity or older age at first birth (older than 35
years) and family history (primarily patients having 2 or more first-degree relatives
with ovarian cancer), including linkage with BRCA1 and BRCA2 genotypes. Some
studies suggest postmenopausal women taking estrogen are also at increased risk.
Conversely, younger age at pregnancy and first birth (25 years or younger), the use
of oral contraceptives, and/or breast-feeding may decrease the risk of ovarian
cancer.
The potential benefit of screening for ovarian cancer is early detection in an effort to
reduce mortality. However, because currently available screening tests do not
achieve high levels of sensitivity and specificity, screening is not recommended for
the general population. At this time, routine screening for ovarian cancer is not
recommended by any medical organization in the U.S. The United States Preventive
Services Task Force (USPSTF) recommends against routine screening for ovarian
cancer. The American Cancer Society (ACS) states that women with a strong family
history of this disease may be screened, but transvaginal ultrasound and CA-125 are
not recommended for screening women without known strong risk factors for ovarian
cancer. Instead of routine screening, the American College of Obstetricians and
Gynecologists (ACOG) suggests that obstetrician-gynecologists remain vigilant for
the early signs and symptoms of ovarian cancer, such as abdominal or pelvic pain
and unexplained weight loss, and that these symptoms be evaluated by pelvic
examination, CA-125, or ultrasound. They found that data suggest that currently
available screening tests do not appear to be beneficial for screening low-risk,
asymptomatic women. Current screening tests for screening women in “high-risk
population” include tumor markers (e.g., CA 125) and imaging methods such as
ultrasound with color Doppler, CT, and MRI. The pelvic examination, which can
detect a variety of gynecological disorders, is not sensitive or specific for detecting
ovarian cancer. In general, ovarian malignancies have disseminated by the time they
are palpable.
Symptoms of early stage disease are often vague and ill-defined, and may not be
severe or specific enough to prompt a woman to seek medical attention. As a result,
the majority of cases of ovarian carcinoma are advanced at the time of diagnosis.
Most affected women have one or more nonspecific symptoms such as lower
abdominal discomfort or pressure, gas, bloating, constipation, irregular menstrual
cycles/abnormal vaginal bleeding, low back pain, fatigue, nausea, indigestion,
urinary frequency, or dyspareunia. Advanced disease is typically associated with
abdominal distention, nausea, anorexia, or early satiety due to the presence of
ascites and omental or bowel metastases; dyspnea may be present due to a pleural
effusion.
Survival from ovarian cancer is related to the stage at diagnosis. About 76% of
women with ovarian cancer survive 1 year after diagnosis, and 45% survive longer
than 5 years after diagnosis. Women younger than age 65 have better 5-year
survival rates than older women. If diagnosed and treated while the cancer has not
spread outside the ovary, the 5-year survival rate is 94%. However, only 19% of all
ovarian cancers are found at this early stage.
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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In contrast to other types of cancer, surgery is always considered for women with
both localized and advanced epithelial ovarian cancer. Unlike many other solid
tumors, effective cytoreduction (“debulking”) conveys a survival benefit among with
women with ovarian carcinoma. The goal of surgery is to establish both an accurate
diagnosis and staging and optimal cytoreduction, leaving no or minimal residual
tumor. Surgical staging is critically important because subsequent treatment and
prognosis will be determined by the pathologic or surgical stage of disease. Ovarian
malignancies are surgically staged according to the 2002 revised American Joint
Committee on Cancer (AJCC) and International Federation of Gynecologic
Oncologists (FIGO) joint staging system:

Stage 1: Cancer is found in one or both of the ovaries and has not spread.

Stage II: Cancer is found in one or both ovaries and has spread into other areas
of the pelvis within the peritoneal cavity (the body cavity that contains
the intestines, the stomach, and the liver).

Stage III: Cancer is found in one or both ovaries and has spread to other parts of
the abdomen within the peritoneal cavity.

Stage IV: Cancer is found in one or both ovaries and has metastasized (spread)
beyond the abdomen to other parts of the body. Cancer that is found
in the tissues of the liver is also considered stage IV.
Initial surgery usually includes a comprehensive staging laparotomy, including a total
abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Based
on published improved outcomes, it is recommended that a gynecologic oncologist
perform the primary surgery. Cytoreductive surgery for patients having clinical
stage II, III, or IV disease remains the initial treatment recommendation. The goal of
primary surgery is to reduce the burden of ovarian cancer to little or no residual
disease (less than 1 cm residual disease.) Procedures that may be considered for
optimal surgical cytoreduction include: radical pelvic dissection, bowel resection,
diaphragm stripping, or splenectomy.
Approximately 75 percent of women with epithelial ovarian cancer present with stage
III or stage IV disease. The standard of care for these patients is surgery followed by
systemic chemotherapy. The recommended initial chemotherapy following debulking
is generally a platinum-and-taxane chemotherapy combination given every 3 weeks
for a period of 18 weeks (6 times over the 18 week period). The platinum drug of
choice is either carboplatin or cisplatin, and the taxane drug (a drug originally
identified from the bark of the Pacific yew tree) is either paclitaxel or docetaxel. The
remaining 25 percent present with stage I or stage II disease are managed initially
with appropriate surgical staging and a maximal cytoreductive procedure. Systemic
chemotherapy may or may not be recommended.
In summary, there is mounting evidence, bolstered by the recent randomized trial,
that in certain patients, intraperitoneal chemotherapy may be superior to traditional
intravenous chemotherapy in the treatment of women with advanced ovarian cancer
who have undergone optimal surgical cytoreduction. Patients should be adequately
counseled about the potential benefits and toxicities associated with IP
chemotherapy so that they may make an informed decision regarding treatment.
The benefit of IP chemotherapy is uncertain in patients with early stage (stage I or
II) ovarian cancer, patients with stage IV disease, patients who have residual tumor
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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greater than 1 cm in diameter and patients with recurrent ovarian cancer. In
addition, further evaluation is needed concerning specific aspects of the treatment,
such as optimal agent, dose, and scheduling.
Review History
May 2007
December 2010
September 2011
August 2012
September 2013
September 2014
September 2015
Medical Advisory Council
Update. Added Medicare Table.
Update – no revisions. Code updates.
Update – no revisions
Update – added intraperitoneal chemotherapy as medically
necessary treatment option for women with optimally debulked
(stage II ovarian cancer, rated as a 2A recommendation from
NCCN 2013). Codes updated.
Update – no revisions
Update – no revisions. Codes updated.
This policy is based on the following evidence-based guidelines:
1. National Cancer Institute. NCI Clinical Announcement on Intraperitoneal Therapy
for Ovarian Cancer. (January 5, 2006).
2. Society of Gynecologic Oncologists. Statement on Use of Intraperitoneal (IP)
Chemotherapy for Ovarian Cancer. January 2006.
3. Society of Gynecologic Oncologists of Canada. Intraperitoneal chemotherapy for
ovarian cancer: A complex strategy but what an exciting avenue!. Jan 2006.
Available at: http://www.gog.org/ipchemoed/GOCPositionStmt.PDF
4. Elit L, Oliver T, Covens A, Kwon J, et al. Gynecology Cancer Disease Site Group.
The role of intraperitoneal chemotherapy in the first-line treatment of women
with stage III epithelial ovarian cancer: a clinical practice guideline. Toronto
(ON): Cancer Care Ontario (CCO); 2006 Aug 3.
5. Hayes. Medical Technology Directory. Intraperitoneal Hyperthermic
Chemotherapy for Peritoneal Carcinomatosis Resulting from Ovarian Cancer,
Peritoneal Mesothelioma, or Abdominal Sarcoma. 2009. Updated February 15,
2012. Update February 4, 2013. Archived June 13, 2014.
6. National Cancer Comprehensive Network (NCCN) Guidelines in Oncology. Ovarian
Cancer, including fallopian tube cancer and primary peritoneal cancer. Version
2.2011. Update Version 2.2012. Update Version 2.2013. Update 3.2014. Update
Version 2.2015.
References – Update September 2015
1.
Tewari D, Java JJ, Salani R, et al. Long-term survival advantage and prognostic
factors associated with intraperitoneal chemotherapy treatment in advanced
ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2015 May
1;33(13):1460-6. doi: 10.1200/JCO.2014.55.9898. Epub 2015 Mar 23.
References – Update September 2014
1.
2.
Al Mutairi NJ, Le T. Does modality of adjuvant chemotherapy after interval
surgical debulking matter in epithelial ovarian cancer?: An exploratory analysis.
Int J Gynecol Cancer. 2014 Mar;24(3):461-7.
Barrios M, Diaz J, Schroeder E, et al. Combination intraperitoneal Carboplatin
and intravenous and intraperitoneal Paclitaxel in the management of advancedstage ovarian cancer. Obstet Gynecol. 2014 May;123 Suppl 1:90S.
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
13
3.
4.
5.
6.
7.
Battelli C, Campo M, Buss MK, et al. Safety and outcome of patients treated
with a modified outpatient intraperitoneal regimen for epithelial ovarian, primary
peritoneal or fallopian tube cancer. Chemotherapy. 2013;59(4):251-9.
Blinman P, Gainford C, Donoghoe M, et al. Feasibility, acceptability and
preferences for intraperitoneal chemotherapy with paclitaxel and cisplatin after
optimal debulking surgery for ovarian and related cancers: an ANZGOG study. J
Gynecol Oncol. 2013 Oct;24(4):359-66.
Bowles EJ, Wernli KJ, Gray HJ, et al. Diffusion of Intraperitoneal Chemotherapy
in Women with Advanced Ovarian Cancer in Community Settings 2003-2008:
The Effect of the NCI Clinical Recommendation. Front Oncol. 2014 Mar 10;4:43.
Robinson W, Cantillo E. Debulking surgery and intraperitoneal chemotherapy
are associated with decreased morbidity in women receiving neoadjuvant
chemotherapy for ovarian cancer. Int J Gynecol Cancer. 2014 Jan;24(1):43-7.
Suidan RS, St Clair CM, Lee SJ, et al. A comparison of primary intraperitoneal
chemotherapy to consolidation intraperitoneal chemotherapy in optimally
resected advanced ovarian cancer. Gynecol Oncol. 2014 Jul 17.
References Update – September 2013
1.
2.
Barlin JN, Dao F, Zgheib NB, et al. Progression-free and overall survival of a
modified outpatient regimen of primary intravenous/intraperitoneal paclitaxel
and intraperitoneal cisplatin in ovarian, fallopian tube, and primary peritoneal
cancer.
Herzog TJ, Armstrong DK. First-line chemotherapy for advanced (stage III or IV)
epithelial ovarian, fallopian tubal, and peritoneal cancer. UpToDate. July 1, 2013.
References Update – August 2012
1.
2.
3.
4.
Konner JA, Grabbon DM, Gersi SR, et al. Phase II study of interaperitoneal
paclitaxel plus cisplatinum and intravenous paclitaxel plus Bevacizumab as
adjuvant treatment of optimal stage II or III epithelial ovarian cancer. J Clinical
Oncology. 2011; 29:4662-4668.
National Institute of Health. U.S. National Library of Medicine. NCI Clinical Alert.
Clinical Advisory: NCI Issues Clinical Announcement for Preferred Method of
Treatment for Advanced Ovarian Cancer. Available at:
www.nlm.nih.gov/databases/alerts/ovarian_ip_chemo.html
Parson EN, Lentz S, Russell G, et al. Outcomes after cytoreductive surgery and
hyperthermic intraperitoneal chemotherapy for peritoneal surface dissemination
from ovarian neoplasms. Am J Surg. 2011 Oct;202(4):481-6. Epub 2011 Apr 7.
Walker JL, Markman M. Intraperitoneal chemotherapy for treatment of ovarian
cancer. UpToDate. June 14, 2012.
References Update - September 2011
1.
2.
3.
Landrum LM, Hyde J Jr, Mannel RS, et al. Phase II trial of intraperitoneal
cisplatin combined with intravenous paclitaxel in patients with ovarian, primary
peritoneal and fallopian tube cancer. Gynecol Oncol. 2011 Jun 10.
Mackay HJ, Provencheur D, Heywood M, et al. Phase ii/iii study of
intraperitoneal chemotherapy after neoadjuvant chemotherapy for ovarian
cancer: ncic ctg ov.21. Curr Oncol. 2011 Apr;18(2):84-90
Muñoz-Casares FC, Rufián S, Arjona-Sánchez A, et al. Neoadjuvant
intraperitoneal chemotherapy with paclitaxel for the radical surgical treatment of
peritoneal carcinomatosis in ovarian cancer: a prospective pilot study. Cancer
Chemother Pharmacol. 2011 Jul;68(1):267-74.
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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References Update – December 2010
1.
2.
3.
Tiersten AD, Lu PY, Smith HO, et al. Phase II Evaluation of neoadjuvant
chemotherapy and debulking followed by intraperitoneal chemotherapy in
women with stage III and IV epithelium ovarian, fallopian tube or primary
peritoneal cancer. Southwest Oncology Group Study S0009; Gynecol Oncol
2009. 112: 444-449. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/19138791
Zeimet AG, Reimer D, Radi AC, et al. Pros and cons of intraperitoneal
chemotherapy in the treatment of epithelial ovarian cancer. Anticancer Res
2009; 29: 2803-2808.
Markman M. An update on the use of intraperitoneal chemotherapy in the
management of ovarian cancer. Cancer J 2009; 15: 105-109.
References Initial
1. Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel
in ovarian cancer. N Engl J Med 2006; 354:34.
2. Elit L, Oliver TK, Covens A, et al. Intraperitoneal chemotherapy in the first-line
treatment of women with stage III epithelial ovarian cancer: a systematic review
with metaanalyses. Cancer. 2007 Feb 15;109(4):692-702.
3. Markman M. Clinical efficacy supporting the role of intraperitoneal drug delivery
in the primary chemotherapeutic management of small-volume residual advanced
ovarian cancer. Semin Oncol. 2006 Dec;33(6 Suppl 12):S3-7
4. Jemal, A, Siegel, R, Ward, E, et al. Cancer statistics, 2006. CA Cancer J Clin
2006; 56:106.
5. Walker J, Armstrong D, Huang H, et al. Intraperitoneal catheter outcomes in a
phase III trial of intravenous versus intraperitoneal chemotherapy in optimal
stage III ovarian and primary peritoneal cancer: A Gynecologic Oncology Group
study. Gynecologic Oncology 100 (2006) 27 – 32
6. Hamilton C, Berek, J. Intraperitoneal chemotherapy for ovarian cancer. Current
Opinion in Oncology. 18(5):507-515, September 2006.
7. Massard C, Lhomme C, Pautier P. Intraperitoneal chemotherapy in first-line
combination treatment for advanced ovarian cancer. Bull Cancer. 2007 Apr
1;94(4):398-404.
8. Nieves L, Currie J, Hoffman J, Sorosky JI. Ototoxicity after intraperitoneal
chemotherapy: a case report. Int J Gynecol Cancer. 2007 Apr 13.
9. Hess LM, Alberts DS. The role of intraperitoneal therapy in advanced ovarian
cancer. Oncology (Williston Park). 2007 Feb;21(2):227-32.
10. Fung-Kee-Fung M, Provencher D, Rosen B, et al. IP Chemotherapy Working
Group on behalf of the Society of Gynecologic Oncologists of Canada.
Intraperitoneal chemotherapy for patients with advanced ovarian cancer: A
review of the evidence and standards for the delivery of care. Gynecol Oncol.
2007 Mar 16
11. Fujiwara K, Armstrong D, Morgan M, Markman M. Principles and practice of
intraperitoneal chemotherapy for ovarian cancer. Int J Gynecol Cancer. 2007
Jan-Feb;17(1):1-20.
12. Wenzel LB, Huang HQ, Armstrong DK, et al. Gynecologic Oncology Group.
13. Health-related quality of life during and after intraperitoneal versus intravenous
chemotherapy for optimally debulked ovarian cancer: a Gynecologic Oncology
Group Study. J Clin Oncol. 2007 Feb 1;25(4):437-43.
Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
15
14. Alberts DS, Delforge A. Maximizing the delivery of intraperitoneal therapy while
minimizing drug toxicity and maintaining quality of life. Semin Oncol. 2006
Dec;33(6 Suppl 12):S8-17.
15. Petignat P, du Bois A, Bruchim I, et al. Should intraperitoneal chemotherapy be
considered as standard first-line treatment in advanced stage ovarian cancer?
Crit Rev Oncol Hematol. 2007 May;62(2):137-147.
16. Burkett AM, Cohn DE, Copeland LJ. Vaginal evisceration during intraperitoneal
chemotherapy for advanced ovarian cancer. Gynecol Oncol. 2007
Feb;104(2):491-3.
17. Kyrgiou M, Salanti G, Pavlidis N, et al. Survival benefits with diverse
chemotherapy regimens for ovarian cancer: meta-analysis of multiple
treatments. J Natl Cancer Inst. 2006 Nov 15;98(22):1655-63.
18. Coleman RL, Sood AK. Historical progress in the initial management of ovarian
cancer: intraperitoneal chemotherapy. Curr Oncol Rep. 2006 Nov;8(6):455-64.
19. Singhal P, Lele S. Intraperitoneal chemotherapy for ovarian cancer: where are
we now? J Natl Compr Canc Netw. 2006 Oct;4(9):941-6.
20. de Bree E, Theodoropoulos PA, Rosing H, et al. Treatment of ovarian cancer
using intraperitoneal chemotherapy with taxanes: from laboratory bench to
bedside. Cancer Treat Rev. 2006 Oct;32(6):471-82.
21. Rufian S, Munoz-Casares FC, Briceno J, et al. Radical surgery-peritonectomy and
intraoperative intraperitoneal chemotherapy for the treatment of peritoneal
carcinomatosis in recurrent or primary ovarian cancer. J Surg Oncol. 2006 Sep
15;94(4):316-24.
22. Hamilton CA, Berek JS. Intraperitoneal chemotherapy for ovarian cancer. Curr
Opin Oncol. 2006 Sep;18(5):507-15.
23. de Bree E, Rosing H, Michalakis J, et al. Intraperitoneal chemotherapy with
taxanes for ovarian cancer with peritoneal dissemination. Eur J Surg Oncol. 2006
Aug;32(6):666-70.
24. Jaaback K, Johnson N. Intraperitoneal chemotherapy for the initial management
of primary epithelial ovarian cancer. Cochrane Database Syst Rev. 2006 Jan
25;(1)
25. Zang RY, Li ZT, Tang J, et al. Weekly induction intraperitoneal chemotherapy
after primary surgical cytoreduction in patients with advanced epithelial ovarian
cancer. World J Surg Oncol. 2006 Jan 19;4(1):4
26. Miyagi Y, Fujiwara K, Kigawa J, et al. Sankai Gynecology Study Group (SGSG).
Intraperitoneal carboplatin infusion may be a pharmacologically more reasonable
route than intravenous administration as a systemic chemotherapy. A
comparative pharmacokinetic analysis of platinum using a new mathematical
model after intraperitoneal vs. intravenous infusion of carboplatin--a Sankai
Gynecology Study Group (SGSG) study. Gynecol Oncol. 2005 Dec;99(3):591-6
27. Yen MS, Juang CM, Lai CR, et al. Intraperitoneal cisplatin-based chemotherapy
vs. intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced
epithelial ovarian cancer. Int J Gynaecol Obstet. 2001 Jan;72(1):55-60.
28. Markman M, Bundy BN, Alberts DS, et al. Phase III trial of standard-dose
intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin
followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume
stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology
Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group.
J Clin Oncol. 2001 Feb 15;19(4):1001-7.
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Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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Intraperitoneal Chemotherapy for Ovarian Cancer Sep 15
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