Intraperitoneal Chemotherapy Chemotherapy Research Articles

Is there a role for intraperitoneal chemotherapy in early stage pelvic high-grade serous carcinoma?

Patients with Stage I/II pelvic high-grade serous carcinoma (HGSC) have significant risk of recurrence and death. Although previous studies demonstrate overall survival benefit with intraperitoneal chemotherapy (IP) in Stage III disease, no studies have evaluated the outcomes in early stage disease. We offered IP chemotherapy (IP/IV) to patients with Stage I/II HGSC from 2009−2022. The objectives was to evaluate recurrence and overall survival in this cohort of patients, compared to those who received standard intravenous (IV) chemotherapy.

A retrospective study comparing the efficacy of dose-dense chemotherapy, intraperitoneal chemotherapy and dose-dense chemotherapy with hyperthermic intraperitoneal chemotherapy in the treatment of advanced stage ovarian carcinoma

ObjectivesHyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP) and dose-dense (DD) chemotherapy have been employed with varying success in the treatment of advanced stage ovarian carcinoma. Despite the clinical benefits associated with these specific forms of chemotherapy administration, they have not been comparatively analyzed, vis-à-vis their efficacy. Study designAdvanced stage ovarian cancer patients who were treated with platinum/taxane chemotherapy via a DD regimen (n = 100), IP approach (n = 81) or a DD regimen in conjunction with HIPEC (n = 64) were retrospectively evaluated. The clinical variables of interest were patient age, body mass index, surgery and pathology data, chemotherapy regimen, inclusion of maintenance therapy, and progression free/overall survival. ResultsProgression free survival (PFS) was significantly more pronounced in the HIPEC (34.9 months) and IP (34.0 months) patients, compared to the DD group (27.6 months) (P = 0.005). A cox-proportional hazards regression model indicated that there was a decreased risk of disease progression accorded to the patients who were treated with IP chemo or HIPEC and DD chemotherapy (HR, 0.43; 95 % CI: 0.21–0.88; P = 0.022) and the subjects who underwent optimal cytoreductive surgery (HR, 2.42; 95 % CI: 1.22–4.80; P = 0.011). Positive BRCA status (HR, 0.434; 95 % CI: 1.59–3.44; P = 0.001) and number of chemotherapy regimens (HR, 1.36; 95 % CI: 1.159–1.61; P = 0.001) were significantly correlated with improved OS although we did not discern a survival benefit associated with any of the chemotherapy treatments (P = 0.136). ConclusionWe observed PFS advantages conferred to the ovarian cancer patients treated with HIPEC and IP chemotherapy compared to DD chemotherapy. However, an overall survival advantage related to the chemotherapy regimens was not borne out, possibly due to the retrospective nature of the study or differing time periods wherein the specific patient cohorts underwent treatment.

Should we use the hyperthermic intraperitoneal chemotherapy in the management of ovarian cancer? A literature review

Rationale: Epithelial ovarian cancer (EOC) is a relatively chemosensitive malignancy which begins, and most frequentlydisseminates by intraperitoneal seeding. Intraperitoneal chemotherapy (IP) is a route of drug delivery that allows the directinfusion of the chemotherapeutic agents into the peritoneal cavity. It has been proven to be efficient and with lower systemic sideeffects in comparison to the intravenous (IV) route. The combination between hyperthermia and intraperitoneal chemotherapy(Hyperthermic intraperitoneal chemotherapy) has a synergistic killing effect on the malignant cells and appears to be feasible inthe treatment of EOC. Objective: To review the current literature and discuss the use of HIPEC in the course of the EOC treatment: as first line medicaltreatment, at the time of cytoreductive surgery (CS), postoperative adjuvant IP chemotherapy and HIPEC, and for recurrentdisease focusing on the survival benefit, mortality rates, morbidity, adverse effects and limitations. Method: Medline, Pubmed, and the Cochrane Central Register of Controlled Trials (CENTRAL ) were investigated for Englishlanguage articles about the role of HIPEC in women with primary EOC, of any FIGO stage. The analysis was restricted toretrospective studies, randomized and nonrandomized controlled clinical trials, and gynecological oncology journals. The selectedinformation included data on feasibility, overall survival (OS), quality of life, and comparison with standard IV chemotherapy interms of complications, toxicity and anticancer effects. Conclusion: Hyperthermia of the IP chemotherapy solution increases the cytotoxicity of the drug in the peritoneal cavity andits systemic effects on the tumor peritoneal nodules. Although initial investigators presented encouraging survival outcomeswhen HIPEC was used in recurrent EOC, further studies are necessary in order to incorporate HIPEC as a front-line treatmentof EOC or as an adjuvant therapy. More research is required for defining the possible roles of HIPEC within the spectrum ofother treatments for EOC including repeated normothermic IP chemotherapy, early postoperative IP chemotherapy, and novel andbiological agents.

Effect of intraperitoneal chemotherapy on survival for ovarian cancer in clinical practice and frequency of use.

5576 Background: In 2006 the National Cancer Institute (NCI) issued a rare clinical alert recommending intraperitoneal chemotherapy (IP) to treat ovarian cancer after GOG-172, a randomized clinical trial comparing IP and intravenous chemotherapy (IV), demonstrated a 16-month survival advantage with IP. The aims of this study were to determine: (1) changes in IP utilization over time, (2) factors associated with adoption of IP therapy, and (3) the impact of IP on survival. Methods: Prospective cohort study of women with stage III, optimally-cytoreduced ovarian cancer treated at National Comprehensive Cancer Network (NCCN) institutions. Trends were evaluated in 823 patients between 2003-2012. In 603 patients, diagnosed after 2006, multivariable logistic regression and propensity-score analyses were used to examine factors associated with receipt of IP therapy and associations between treatment modality, adverse events, and overall survival. Results: IP utilization rose from 0% to 33% between 2003-2006, increased to 50% in 2007-2008, and decreased to 43% during 2009-2012. At treatment initiation 43% of patients received modified IP regimens, 29% received the GOG 172 regimen, and 28% received IP on a clinical trial. In adjusted analyses, younger age, fewer comorbid conditions, and clinical trial enrollment were associated with IP therapy (all P≤0.01). NCCN center was independently associated with receipt of IP; the adjusted proportion of patients receiving IP varied by site between 16% and 71% (P<0.001). After propensity-score weighted adjustment, patients receiving IP were more likely to switch to IV due to toxicity (AOR=2.01, 95% CI=1.30-3.12) compared with IV. Adjusted 5-year overall survival rates were 57% for IP vs. 44% for IV (hazard ratio=0.69, 95% CI=0.50-0.94). Conclusions: The use of IP therapy increased significantly over the past decade at NCCN centers. However, recently only a minority of eligible patients have received it. Despite frequent modifications, IP chemotherapy is associated with significantly improved survival in clinical practice. Future studies should examine whether site-specific variations in IP utilization reflect patients’ informed treatment preferences.

2:26 PM Abstract No. 203 - Intraperitoneal chemotherapy catheter placement using percutaneous technique in patients without ascites

Purpose The addition of intraperitoneal chemotherapy (IP) to intravenous chemotherapy (IV) for the treatment of advanced ovarian cancer has demonstrated improved survival in comparison to IV chemotherapy alone. Traditionally, IP catheters where placed surgically with reported complications in 9.6% to 34% of patients. We seek to review the outcomes of using a percutaneous IP catheter placement technique in patients without ascites. Materials and Methods IP catheter placement was carried out while undergoing conscious sedation. Ultrasound guidance was initially used to access the peritoneal cavity over the right lobe of the liver. A 5 Fr catheter was placed into the IP cavity and the abdomen was distended with carbon dioxide. Under fluoroscopic guidance, the abdominal right upper quadrant was accessed at the site of the accumulation of gas, thus avoiding potential injury to bowel. A 14.3 Fr multi side-holed catheter was then placed into the pelvis with the port reservoir tunneled over the anterior chest wall subcutaneous tissues. We retrospectively reviewed all patients who received percutaneous IP catheter placement from 12/2008 through 8/2012. Results Twenty-three patients underwent percutaneous IP catheter placement. One patient (4.3%) had an intra-procedural complication although the catheter was ultimately placed. Fourteen patients (60.8%) completed IP chemotherapy. Four patients (17.4%) continue to receive IP chemotherapy. One catheter (4.3%) was removed due to a catheter related infection. Four patients (17.3%) had their catheters removed for reasons unrelated to the IP catheter: two due to side effects from chemotherapy, one due to sepsis caused by perforated diverticulitis that was felt to be unrelated to the IP catheter by the surgeon who preformed the exploratory laparotomy, and the last due to sepsis from an infected IV catheter which did not involve the IP catheter. Conclusion Percutaneous placement of IP catheters in patients without ascites using carbon dioxide insufflation has a high technical success rate with low risk of catheter-related complications. This procedure offers a viable alternative to traditional surgical placement.

Causes of discontinuation of intraperitoneal chemotherapy in patients with ovarian cancer.

e15570 Background: Intraperitoneal chemotherapy (IP) showed benefit in efficacy in patients with ovarian cancer but with high rates of complications and/or toxicity. We reviewed our experience and the identification of factors for discontinuing treatment. Methods: We conducted a retrospective review of electronic medical records of patients undergoing IP catheter placement at our medical center from May 2006 to December 2012; our institutional protocol for stages II/III ovarian carcinoma after optimal surgical resection is the following: 2 cycles of IV carboplatin/paclitaxel follow by 4 cycles of IP chemotherapy (paclitaxel 135 mg/m2 day 1 IV, cisplatin 75mg/m2 day 2 IP, paclitaxel 60mg/m2 day 8 IP). For statistical analysis, we used Fisher's exact test. Results: Thirty-seven patients underwent IP catheter placement. Median follow-up was 31.2 months. Eight patients did not receive IP chemotherapy: 3 patients for stage I, 2 patients stage IV, 1 patient synchronous breast cancer, one for unusual histology, and 1 patient for partial bowel obstruction. IP chemotherapy was administered to 29 patients. In total, 94 cycles IP chemotherapy were given with a median of 3 cycles per patient. IP chemotherapy was completed as planned in 24 patients (82.7%). The reason for treatment discontinuation: abdominal pain in 2 patients, extravasation in 1 patient, one patient due to peptic stricture, and other for esophageal ulcer. Grade 3-4 toxicity for IP chemotherapy was observed in 20% of patients. Median body mass index (BMI) was 24.3. IP chemotherapy was completed as planned in 94% of patients with BMI&lt;25 and in 64% of patients with BMI&gt; 25, p &lt;0.05. Conclusions: This modified IP chemotherapy regimen is feasible with acceptable toxicity. Most patients completed the scheduled treatment with IP. BMI &gt; 25 was identified as a possible risk factor for discontinuation of treatment.

A Gynecologic Oncology Group Study of serum CA-125 levels in patients with stage III optimally debulked ovarian cancer treated with intraperitoneal compared to intravenous chemotherapy: An analysis of patients enrolled in GOG 172

ObjectiveSerum CA-125 values have been advocated in the monitoring of ovarian cancer patients receiving intravenous (IV) chemotherapy. This evaluation sought to determine if the CA-125 test can be used to monitor treatment effect among patients receiving intraperitoneal chemotherapy (IP). MethodsPatient charts from a phase III clinical trial (GOG 172) were retrospectively reviewed. Serum CA-125 levels prior to each cycle of therapy were collected and compared between the IV and IP chemotherapy delivery. The association between CA-125 and progression-free survival (PFS) or overall survival (OS) was estimated and the homogeneity of the results between IP and IV chemotherapy was assessed. ResultsA total of 177 patients were treated with IV chemotherapy and 165 patients with IP chemotherapy with CA-125 data available were included in this analysis. The observed difference was not statistically significant in median CA-125 levels between the IV and IP arms at any time point (P > 0.05 for all). Following surgery and adjuvant chemotherapy, patients with an abnormal CA-125 > 35 U/ml were 2.45 times more likely to have disease progression (95% CI: 1.52–3.95, P < 0.001) and 2.78 times more likely to die of disease (95% CI: 1.66–4.65, P < 0.001), compared to those with a CA-125 < 35 U/ml. These results were consistent with IP and IV chemotherapy. ConclusionSerum CA-125 levels decrease in a similar manner during IP chemotherapy when compared to IV chemotherapy. Serum CA-125 algorithms for monitoring treatment effect that have been established for IV chemotherapy may also be applied for patients receiving IP chemotherapy.

Incidence of intestinal obstruction following intraperitoneal chemotherapy for ovarian tubal and peritoneal malignancies

Objectives To report the incidence of intestinal obstruction after intraperitoneal chemotherapy (IP) in women with ovarian, tubal, or peritoneal malignancies, and determine the frequency of malignant versus adhesion-related obstruction. Methods Patients who were treated with at least one dose of IP chemotherapy between 1986 and 1997, and who had at least 3 month follow-up, were included. Data regarding admissions for gastrointestinal obstruction complaints, radiologic diagnosis of intestinal obstruction and medical or surgical management of obstruction were recorded. Results We identified 334 patients; 307 met our inclusion criteria. A total of 104 (34%) patients developed symptomatic intestinal obstruction after IP therapy commenced. The overall incidence of adhesion-related or mechanical bowel obstruction was only 4%. In the group of patients with a mechanical bowel obstruction, the median time to diagnosis of obstruction was 21 months (range, 2–51) after initiation of IP treatment. Surgical intervention to relieve the obstruction was performed in 6 (50%) patients diagnosed with adhesion-related bowel obstruction. Similarly, in those diagnosed with a malignant bowel obstruction, 42 (48%) were taken to the operating room in an attempt to relieve the obstruction. Conclusion Intestinal obstructions developed in a third of patients who received IP therapy as part of their treatment for advanced ovarian, tubal, or peritoneal cancer. However, the majority of the obstructions are related to progression of malignant intra-abdominal disease. Only 4% of the patients develop intestinal obstruction due to intestinal adhesions after IP treatment.

Platinum and taxane intraperitoneal chemotherapy after secondary cytoreductive surgery for recurrent ovarian carcinoma

16043 Background: Intraperitoneal chemotherapy (IP) after primary optimal debulking for advanced stage epithelial ovarian carcinoma improves survival. The objective of this research is to describe our experience with IP taxane and platinum chemotherapy after optimal secondary cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer. Methods: We retrospectively reviewed charts from January 2006 to January 2007 and identified approximately 30 patients who received IP chemotherapy for optimally debulked advanced ovarian carcinoma. Of these patients, 8 were treated at first recurrence with cytoreductive surgery followed by second-line IP chemotherapy with intravenous docetaxel (70 mg/m2) and IP cisplatin (75–85 mg/m2) on day 1 and IP paclitaxel (60 mg/m2) on day 8, every 21 days. Results: The median disease free interval from completion of initial chemotherapy to recurrence was 19 months. All patients who underwent secondary cytoreductive surgery were considered optimally debulked (less than 1 cm residual disease), with 6 patients having no residual disease. One patient required rectal resection and another patient had ileocecal resection without a protective ostomy. All patients had insertion of an intraperitoneal venous access device for infusion of IP chemotherapy at the time of cytoreduction. While four patients have completed all 6 cycles of IP chemotherapy, one patient completed only 3 cycles due to catheter related toxicity requiring removal of the port (abdominal pain). This patient did not undergo concurrent bowel surgery. In addition, two patients have completed 3 cycles and two patients are currently scheduled to begin IP chemotherapy. Only two patients experienced grade 3 or 4 neutropenia. No other grade 3 or 4 toxicities were identified. A median of 5 cycles (range 2–5 cycles) was required to achieve a CA125 nadir. Complete clinical response was obtained in all patients at a median follow up of 9 months (range 4–10 months). Conclusions: In optimally debulked, platinum-sensitive patients following secondary cytoreductive surgery for recurrent ovarian cancer, intraperitoneal taxane and platinum chemotherapy is feasible with acceptable toxicity and provides another option for treatment. No significant financial relationships to disclose.

Chimiothérapie intrapéritonéale et cancer de l’ovaire : l’un des nouveaux standards en première ligne ?

The aim of intraperitoneal chemotherapy is to increase chemotherapy activity in exposing tumor to important cytotoxic drug concentration one to several logs greater with regional treatment. Intraperitoneal chemotherapy (IP) is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. This may increase the anticancer effect with fewer systemic adverse effects to comparison to intravenous therapy. In ovarian cancer, intraperitoneal chemotherapy has been used in second line treatment, in consolidation, and in first-line combination. The most recent trial conducted by the Gynecologic Oncology Group (GOG) study, a phase III randomised trial and reported by Armstrong et al. published in the New England Journal of Medecine in 2006, demonstrated that IP chemotherapy improves survival in patients with surgically treated ovarian cancer when added to intravenous therapy, compared with IV therapy alone. This study could change the standard treatment in advanced ovarian cancer. Despite increased toxic effects and the more complicated logistics of the drug administration, the data from GOG trial establish IP chemotherapy as an important advance in the first-line treatment of patients with optimally debulked stage III disease.