Intraperitoneal chemotherapy for treatment of ovarian cancer

INTRODUCTION — The most common route of ovarian cancer spread is within the peritoneal cavity. The rationale for administering chemotherapy directly into the peritoneal cavity is supported by preclinical, pharmacokinetic, and pharmacodynamics data. Compared with intravenous (IV) treatment, intraperitoneal (IP) administration permits a several-fold increase in drug concentration to be achieved within the abdominal cavity. In addition, some clinical trials have demonstrated a survival advantage to the incorporation of IP treatment in the upfront management of ovarian cancer.

The rationale and technical issues related to IP chemotherapy for ovarian cancer will be reviewed here. A more extensive discussion on the data to support the use of IP treatment in ovarian cancer is covered separately. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging" and "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer".)

RATIONALE — In the vast majority of patients, epithelial ovarian cancer (EOC, which includes fallopian tube and peritoneal cancers) is confined to the peritoneal cavity at initial diagnosis and in recurrence [1]. Because of this natural history, ovarian cancer is an ideal target for IP therapy. Pharmacokinetic studies have demonstrated that IP administration of chemotherapy results in high peritoneal to plasma ratios for peak concentration for cisplatin, paclitaxel, carboplatin, and docetaxel [2]. The higher peritoneal concentration is hypothesized to improve efficacy by increasing concentration of the cytotoxic agent in the tumor microenvironment. Analysis of intratumoral drug concentrations demonstrates that lesions 2 to 3 mm or smaller will have significantly higher drug exposure from intraperitoneal administration as compared with intravenous administration [3]. In addition, avascular tumors are exposed to higher drug concentrations with intraperitoneal compared with intravenous delivery, while systemic exposure and associated toxicity is minimized [4,5]. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer", section on 'Women with optimally cytoreduced disease'.)

PATIENT SELECTION

Indications for IP chemotherapy — Based on available clinical data, IP chemotherapy may be most useful in women with optimally debulked (to ≤1.0 cm) stage III epithelial ovarian cancer (EOC). Some patients with earlier-stage disease may also be candidates (see "Adjuvant therapy of early-stage (stage I and II) epithelial ovarian, fallopian tube, or peritoneal cancer", section on 'Selection of patients'). Those patients who have been cytoreduced to no gross residual disease seem to have the greatest benefit from IP chemotherapy and improved overall survival.

Furthermore, some experts also utilize IP chemotherapy for women treated with neoadjuvant chemotherapy who undergo an optimal interval cytoreduction. However, there are no prospective data to evaluate this strategy, and we await data from the OV.21 trial to inform this decision [6]. The management and choice of chemotherapy for EOC is discussed separately. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer".)

IP therapy is likely best suited to patients with no or minimal residual disease after surgical cytoreduction because penetration of chemotherapy into tumor tissue is limited to a few millimeters of tumor on the peritoneal surface layers. While impact of minimal residual disease on efficacy of IP chemotherapy was not shown in a subgroup analysis of one large phase III trial [7], most data from phase II and phase III trials support the tenet that minimal residual disease is key to maintaining efficacy [8-12]. Moreover, at least two meta-analyses have suggested benefit of IP therapy as part of first-line treatment for women with optimally cytoreduced EOC in terms of both progression-free and overall survival [13,14]. These data are reviewed in more detail separately. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer", section on 'Women with optimally cytoreduced disease'.)

There is wide agreement that IP chemotherapy should not be administered in the setting of stage IV EOC or tumors that have not been optimally debulked (residual tumor greater than 1 cm in diameter (table 1)). However, a phase II study of 26 patients demonstrated efficacy of IP chemotherapy in women with residual lesions ≥2 cm [15]. A randomized phase II/III trial of IP chemotherapy in women with ovarian cancer who have undergone suboptimal debulking surgery is ongoing [16].

Contraindications — Contraindications for IP chemotherapy include:

●Inability to tolerate cytoreductive surgery

●Active peritonitis or sepsis

●Extensive intraabdominal adhesions, which prevent adequate distribution of instilled chemotherapeutic agents

●Obvious peritoneal contamination

●Inadequate renal function for cisplatin clearance

●Inability to undergo the schedule of IP chemotherapy administration

Bowel resection is not a contraindication to IP port placement; however, it is sensible to avoid port placement in the presence of gross peritoneal contamination by bowel contents. (See 'Patients undergoing bowel resection' below.)

Older age is not necessarily a contraindication to IP chemotherapy (however, women 70 years of age and older may tolerate fewer cycles of IP chemotherapy than their younger counterparts given decreased renal clearance of cisplatin [17]). (See "The approach to ovarian cancer in older women", section on 'Intraperitoneal chemotherapy'.)

TECHNICAL ISSUES

Timing of placement — The IP port/catheter can be placed concomitant with surgical staging and cytoreduction or at a later time as a second procedure. Delayed placement of the port/catheter is performed via laparoscopy, mini-laparotomy, or interventional radiology at a second procedure, usually performed a few weeks after the primary surgical debulking [18,19].

The timing varies depending on the patient, preoperative counseling, and the preferences of the oncology team. The timing does not appear to impact the probability the patient will complete the prescribed treatment [20].

Factors to consider include:

●Placement at the time of staging avoids the risks and morbidity of a second procedure, particularly in patients with adhesions.

●Prior to the initial staging and surgical treatment procedure, the diagnosis of epithelial ovarian cancer (EOC) has not been established in many patients and is confirmed only during surgery based upon frozen section. Also, patients with apparent stage I disease preoperatively are often found at surgery to have micrometastasis of the omentum, extrapelvic peritoneum, and/or lymph nodes. The stage determines whether chemotherapy is required. Thus, for the IP port to be placed, the patient must be counseled about chemotherapy treatment, toxicities, and delivery options in the absence of complete diagnosis and staging.

Deferring placement of the IP port until after the pathology has been confirmed allows the clinician to review the final pathology and enter into a shared decision-making conversation about whether the patient would like to proceed with IP chemotherapy.

Patients may change their decision regarding IP chemotherapy after surgery. As an example, a patient may decide against an IP port preoperatively because she lives too far from a center that offers IP chemotherapy. Many times, the patient changes her mind and at the postoperative visit and requests to be treated with IP chemotherapy.

IP catheter and port — The device typically consists of a port and a catheter. A subcutaneous pocket is created and the port is sutured to the anterior abdominal fascia and remains accessible to allow instillation of chemotherapeutic agents. Connected to the port is the catheter, which is within the peritoneal cavity.

IP catheters come as either single-lumen or fenestrated catheters. There are little data comparing these, but one case series reported that they are both associated with a low rate of complications [21]. In addition, IP catheters are available preattached to the port, or unattached, and the surgeon can choose his or her preference.

At our centers, we utilize the single-lumen implanted port with a silicone peritoneal catheter (14.3 French) or a fully implantable power port attached to a single-lumen, radiopaque, polyurethane venous catheter of large size (8 French or higher). In our experience, these catheters have a lower likelihood of kinking or obstructing flow than other port-a-caths used for peritoneal or intravenous access [18]. We base the type of port on the thickness of subcutaneous adipose tissue. The power port is larger in size and more easily accessible post-placement and therefore may be more suitable for women with more adipose tissue on the abdominal wall.

We do not use peritoneal catheters designed for dialysis (eg, Tenckhoff catheters) because they may increase the risk of bowel complications in these patients. In addition, since the catheter is only needed for infusion and not for the withdrawal of fluid, this type of catheter is not necessary. Furthermore, the Dacron cuff on Tenckhoff dialysis catheters may erode into the peritoneal cavity and be associated with bowel obstructions. There appear to be some catheter materials that may encourage the formation of fibrous sheaths and bowel adhesions, which can make them difficult to remove at the end of therapy [22].

Procedure — To place the port and catheter at the time of staging surgery, a subcutaneous pocket is created for the port at the level of the abdominal fascia and port is sutured to the fascia; the port needs to be easily palpable and accessible. This is placed via a 3 to 4 cm skin incision over the lower left or right costal margin at the midclavicular line [23]. Some centers prefer to locate the port on top of the costal margin to provide a backstop to facilitate access.

The catheter is inserted through a separate stab incision and is tunneled at the level just above the fascia and below the subcutaneous adipose tissue until it reaches the port pocket. This is done with a tunneling device. A guide wire is used to insert the catheter end into the peritoneal cavity. The other end of the catheter is attached to the port. The catheter should be placed where the formation of adhesions is least likely to occur, keeping in mind what tissues were removed and where peritoneal stripping was required. If a rectosigmoid resection and mobilization of the splenic flexure has been performed, then the right side should be chosen. If the terminal ileum and right colon has been resected, then the left side should be chosen. It is important to remember to expect the transverse colon to be adherent to the anterior abdominal wall after a complete omentectomy procedure. For this reason, the entry into the abdominal cavity should be at or below the umbilicus, avoiding the midline incision. The chosen site should be ipsilateral to the IP port incision and about 6 cm lateral to the umbilicus.

Once the catheter is placed and connected to the port, all incisions are closed. Careful attention to abdominal wall closure with a watertight closure to prevent leaking of ascites or IP chemotherapy is also very important. For patients in whom entry into the vagina is required, the vaginal cuff should be closed with delayed absorbable suture to create a watertight seal [18].

Delayed insertion can be performed at a second surgical procedure, or by interventional radiology, provided the expertise is locally available. What follows is the procedure for IP port placement at a second surgical procedure, either laparoscopically or by mini-laparotomy. We prefer laparoscopic over mini-laparotomy placement of the IP port and catheter.

CHEMOTHERAPY ADMINISTRATION

Initiation — IP chemotherapy infusions have been given in the operating room or as early as 24 hours postoperatively. However, the fluid shifts that surround aggressive surgical debulking make renal toxicity a major concern, particularly if performed too early. Therefore, we and others suggest waiting until the patient has resumed normal bowel function (ie, postoperative ileus has resolved) and has recovered enough to be sure there are no signs of perioperative complications [24]. For patients in whom the IP port was placed at a second surgical procedure (or was otherwise delayed), treatment may begin 24 hours after an IP catheter has been placed. Treatment approach and protocols for ovarian cancer are discussed separately. (See "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tube, and peritoneal cancer" and "Treatment protocols for gynecologic malignancies" and "Treatment protocols for gynecologic malignancies", section on 'Regimens for ovarian cancer'.)

Patients undergoing bowel resection — We place an IP port at the time of debulking surgery that includes bowel resection. In this scenario, we prefer to give the first cycle of chemotherapy intravenously (IV) and start the IV/IP regimen with the second cycle. Giving IV chemotherapy initially allows for complete healing of the bowel anastomoses before initiating IP chemotherapy. If the patient tolerates treatment well, she will receive six cycles of IV/IP chemotherapy (making a total of seven cycles of adjuvant chemotherapy).

This practice avoids a second surgery for IP port placement, and does not appear to increase complication rates or the rate of patients not initiating IP treatment. In a retrospective review comparing 306 patients with ovarian cancer who underwent IP port placement with or without concurrent bowel resection, both groups had similar rates of IP port utilization for chemotherapy (approximately 80 percent) and a similar total number of chemotherapy cycles (median, three cycles) [25]. The two groups also had similar IP port complication rates (19.2 versus 23.2 percent), although the study was underpowered to detect a statistically significant small difference.

Intravenous hydration — For patients receiving IP cisplatin, saline infused intraperitoneally is not adequate hydration to prevent renal toxicity. Intravenous prehydration with a liter of normal saline is given to ensure adequate urine output of 100 mL per hour before administration of the IP cisplatin to prevent renal toxicity.

Following administration of IP cisplatin, post-intravenous hydration with another liter of normal saline is recommended to prevent renal toxicity, with an aim to maintain urine output of 100 cc per hour. Furosemide or mannitol can be utilized if the appropriate balance of input and output is concerning and the patient is not dehydrated. It must be emphasized that because of the fluid required to administer IP therapy safely, patients with heart disease need to be closely monitored.

Other helpful information for health professionals on administration of IP chemotherapy is available online from NRG Oncology.

Technique — The technique of IP chemotherapy administration is as follows:

●Patients administered either IP cisplatin or paclitaxel should receive the same supportive care drugs used with IV administration of these agents.

•For patients receiving IP cisplatin, premedications include diphenhydramine, cimetidine, dexamethasone, ondansetron or equivalent, and aprepitant. (See "Prevention of chemotherapy-induced nausea and vomiting in adults" and "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Neurokinin-1 receptor antagonists'.)

•Delayed nausea is common following IP administration of cisplatin. The specific antiemetic regimen should be chosen to maximize control of both acute and delayed emesis (ie, three days of aprepitant in combination with a long-acting serotonin receptor antagonist plus three to four days of oral corticosteroids).

The nausea and vomiting associated with cisplatin will increase the chance of renal toxicity if not adequately prevented. (See 'Nephrotoxicity' below.)

•Routine premedications, including antihistamines and dexamethasone, should be given before paclitaxel administration to prevent hypersensitivity reactions. (See "Infusion reactions to systemic chemotherapy", section on 'Taxanes'.)

●Prior to accession of the IP port, it is useful to apply a topical anesthetic, such as liposomal lidocaine (applied 30 minutes prior to the procedure) or EMLA cream (applied 60 minutes prior to the procedure).

●Chemotherapy should be administered into the IP port using a 19 or 20 gauge right-angled needle (eg, Huber needle). At our institutions, we mix chemotherapy in 1 liter of warmed (37°C) normal saline, predominantly to ensure patient comfort. Treatment should be infused under gravitational flow alone. A second liter of saline should be instilled as tolerated, which helps drug distribution. However, this should be stopped if the patient becomes too uncomfortable. (See 'Abdominal pain' below.)

●During infusion, we place patients in a supine or semi-Fowler position with her head no higher than 30 degrees above the bed, both for comfort and to prevent dislocation of the needle. After the infusion (and during the second liter of hydration), we reposition the patient from side to side every 15 minutes for one hour to help disperse the infusate.

●After administration of chemotherapy, the port and catheter are flushed with at least 10 mL of heparin 100 units/mL. The needle can then be removed and the site occluded with a pressure dressing to prevent leakage of the infusate from the port. The dressing can be removed after 12 hours.

COMPLICATIONS — Patients undergoing IP chemotherapy should be regularly assessed for abdominal pain, catheter-related problems and signs of infection, neurotoxicity, renal toxicity, and myelosuppression. We do not routinely administer growth factor support during the first cycle.

In general, there are two types of complications seen in women undergoing IP therapy: those related to the drugs themselves and those related to the port. These are discussed below.

Chemotherapy-related — The complications of treatment are specific to the agents utilized. For patients with ovarian cancer, this primarily includes neurotoxicity and cisplatin-related nephrotoxicity. In addition, the volume of fluid required for delivery is a frequent cause of abdominal pain, which if severe may warrant discontinuation of treatment.

Nephrotoxicity — Renal toxicity is a well-described risk of cisplatin treatment, and women receiving IP cisplatin are at higher risk than those receiving IV treatment alone. As an example, in Gynecologic Oncology Group (GOG) 172, the incidence of serious (grade 3/4) renal toxicity was higher in those receiving IP treatment compared with standard (IV) treatment (7 versus 2 percent) [11]. Avoiding cisplatin-related nephrotoxicity requires that the clinician pay close attention to hydration status and emesis prophylaxis. (See 'Intravenous hydration' above.)

The first cycle is usually the most challenging. This is because many women are undernourished, with a low albumin level, peripheral edema, and ascites. Poor intravascular volume may lead to fluid shifts to the third space. Avoiding dehydration through close attention to volume status and adequate antiemetic therapy will help to prevent renal toxicity. Within two to three weeks, the nutritional condition of the patient will likely be markedly improved, and these fluid shifts will resolve.

If renal insufficiency develops, treatment should be withheld until renal function improves [24]. In GOG trial 172, creatinine clearance was measured if the serum creatinine rose to ≥2 mg/dL. Subsequent treatment was held if the creatinine clearance was less than 50 mL/min and only resumed when it rose above 50 mL/min. The tolerability of the regimen may be substantially improved by reducing the IP cisplatin dose to 75 or 80 mg/m² [18]. IP carboplatin (area under the curve [AUC] of 6) is a suitable substitute for IP cisplatin. In the GOG 252 trial [26], the median progression-free and overall survivals were similar in the IP carboplatin and IP cisplatin arms. Although mean patient-reported Functional Assessment of Cancer Therapy (FACT)-Neurotoxicity scores were similar in all treatment groups, mean Trial Outcome Index of the FACT-Ovary scores during chemotherapy were worse in the IP cisplatin arm.

Neurotoxicity — Neurotoxicity is a major issue for patients receiving IP therapy, especially if both cisplatin and paclitaxel are administered. In GOG 172, IP treatment resulted in significantly worse neurotoxicity at three to six weeks after the completion of chemotherapy and one year later when compared with IV therapy [11].

Cisplatin dose reduction (to 75 or 80 mg/m²) when symptoms are first observed may permit more cycles of IP cisplatin to be administered. However, neurotoxicity may warrant discontinuation of therapy and converting to carboplatin (delivered IV) and/or docetaxel for paclitaxel. (See "Overview of neurologic complications of conventional non-platinum cancer chemotherapy" and "Overview of neurologic complications of platinum-based chemotherapy" and "Prevention and treatment of chemotherapy-induced peripheral neuropathy".) 

Abdominal pain — Abdominal pain is more common and often more severe with IP therapy compared with IV treatment alone. It is thought to be related to stretching and distention of bowel-to-bowel adhesions or from intercostal nerve irritation, both resulting from the volume of fluid instilled [27]. However, the possibility of peritonitis or gastrointestinal injury should be considered if there is rebound, guarding, nausea, vomiting, diarrhea, fever, or an elevated white blood cell count. (See 'Gastrointestinal complications' below.)

If pain is encountered, the second liter of IP normal saline after drug infusion may be reduced in volume or eliminated, or the rate of flow can be reduced. In the GOG 172 randomized trial of women with stage III ovarian or peritoneal carcinoma, chemotherapy doses were reduced for patients reporting grade 2 abdominal pain (table 2). Discontinuation of IP treatment was mandated for those with grade 3 abdominal pain (observed in 5 percent of patients) or recurrent grade 2 abdominal pain despite dose reduction [7]. Low-grade abdominal pain can usually be treated with non-opioids such as Tylenol or nonsteroidal anti-inflammatory drugs (NSAIDs) [28].

Abdominal pain appears to resolve once IP treatment is completed. In GOG 172, abdominal pain scores were significantly worse prior to the fourth cycle of IP compared with IV treatment [11]. However, one year after completion of treatment, there was no difference in pain scores between the two arms.

Hypersensitivity reaction — Given that use of IP therapy is generally limited to the first-line setting in which hypersensitivity reactions are rare, little data exist regarding management of such reactions. Hypersensitivity reactions are occasionally observed among the few patients who continue with IP platinum therapy (ie carboplatin or cisplatin) in the setting of recurrent ovarian cancer. They may present as dyspnea, rash, or hypotension. In these situations, it is our approach to discontinue IP chemotherapy and avoid re-exposure to the offending agent in future treatments. In the acute setting of a hypersensitivity reaction, the event may become more serious over time, given the prolonged exposure to drug in the peritoneal cavity. Women experiencing ongoing symptoms should be admitted to an inpatient setting for observation and should receive additional normal saline in the abdominal cavity in an effort to dilute the concentration of drug. If the hypersensitivity reaction progresses or is prolonged, we advise a low threshold to proceed with removal of the fluid using large volume paracentesis.

Catheter-related — Catheter-related problems are frequent and may necessitate premature discontinuation of IP chemotherapy.

In the GOG 172 randomized trial of women with stage III ovarian or peritoneal carcinoma, 119 women in the IP chemotherapy group did not complete the entire six courses of therapy, and catheter-related problems were the primary reason in 40 of these patients and a contributing cause in another 10 patients [20]. These problems included catheter-related infection (25 patients), a blocked catheter (10 patients), leakage around the port or into the subcutaneous tissues (five patients), access problems (eight patients), and vaginal leakage of infusion fluid (in two). Similar complication and completion rates were seen in other studies [20,28]. Others also report a low incidence of bowel injury (0 to 2 percent) [20].

Inability to access port or infuse the drug — Inability to access the port or infuse the drug into the peritoneal cavity is best evaluated using fluoroscopy. Once the Huber needle is directed through the diaphragm of the port into the reservoir, contrast can be injected. The patient is then observed with fluoroscopy to ensure the integrity and patency of the catheter and to see whether contrast flows into the peritoneal cavity. This procedure may also demonstrate adhesions, retrograde flow of dye along the catheter into the port pocket, and dye entering the gastrointestinal tract.

Management depends on the specific problem that is identified:

●Rotational problems can usually be corrected in an outpatient surgery suite by making a small incision over the port under local anesthesia and suturing it in the correct position.

●A kinked catheter can be repaired. In general, this problem is far more common with 6 French (Fr) catheters (which are not recommended for this reason) than they are with the sturdier 9.6 or 14.3 Fr silicone catheters.

●If the catheter has been cut by the Huber needle during failed attempts to access a port, the hole in the catheter can be surgically corrected, allowing IP chemotherapy to resume.

●A blocked catheter or the demonstration of retrograde flow at the port or where the catheter perforates the peritoneum is often caused by adhesions blocking free flow into the peritoneal cavity. Such problems usually require removal of the catheter, as most blockages are due to adhesions or a fibrous capsule around the catheter and are not correctable without choosing a new peritoneal infusion site. An alternative site for catheter placement on the opposite side of the abdomen can be considered if the patient is willing.

Overall, replacing a malfunctioning port allows approximately 50 percent of patients to complete their planned IP therapy, but requires a committed patient and surgeon. When access problems are encountered, chemotherapy can be given intravenously, at least temporarily, to prevent delay of treatment.

Contraindications to replacement include peritonitis, an infected port, intraabdominal abscess, bowel injury, or fistula.

Leakage of infusate — Leakage of infusate through the vaginal and abdominal surgical wounds may cease when these wounds heal; IP infusion may need to be delayed in such patients. In such cases, chemotherapy can be given intravenously, at least temporarily, to prevent delay of treatment.

Gastrointestinal complications

Diagnostic evaluation — Abdominal pain is a common complaint during therapy and is usually related to the infusion and distention of the abdomen (see 'Abdominal pain' above). However, the possibility of peritonitis or gastrointestinal injury should be considered if there is rebound, guarding, nausea, vomiting, diarrhea, fever, or an elevated white blood cell count.

The possibility of these complications can be evaluated by irrigating the catheter with 50 mL of normal saline, aspirating, and sending the specimen for cell count and culture [18]. (See "Evaluation of adults with ascites", section on 'Initial ascitic fluid tests'.)

An upright abdominal radiograph is useful for looking for free air related to perforated bowel. While it is possible that free air may be caused by inadvertent IP administration of air from the infusion line, further evaluation is indicated to exclude more worrisome etiologies if free air has been observed on radiograph. The evaluation should include computed tomography (CT) with oral and IV contrast or immediate surgical evaluation if history and exam are particularly concerning. Additionally, injecting the port with a water-soluble radiographic contrast agent can demonstrate flow into the gastrointestinal tract (implying bowel injury) on rare occasions.

Radiographs may also reveal the catheter in the lumen of the bowel; however, this does not necessarily imply the need for laparotomy to repair the bowel, as long as peritonitis is absent. Sealing of the bowel can occur spontaneously, and this situation has been successfully treated with removal of the catheter alone. However, management of this complication must be individualized.

Peritonitis — If an intraabdominal infection develops, the port and catheter should be removed. Initially, broad spectrum antibiotic therapy with coverage for both skin and gastrointestinal flora is indicated with tailoring of the regimen to cover subsequently identified pathogens [18]. The diagnosis and treatment of bacterial peritonitis is further discussed elsewhere. (See "Spontaneous bacterial peritonitis in adults: Diagnosis", section on 'Distinguishing spontaneous from secondary bacterial peritonitis' and "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis".)

Bowel obstruction — In one series, intestinal obstruction developed in 34 percent of patients after IP chemotherapy commenced, but the majority of cases were related to progression of malignant intraabdominal disease [29]. Only 4 percent of patients had intestinal obstruction that was related to adhesions from IP treatment.

Gastrointestinal necrosis or perforation — Gastrointestinal necrosis and perforation have been associated with postoperative administration of paclitaxel, both intravenously and intraperitoneally [30,31]. It is possibly related to subclinical surgical complications or impaired host defense and repair mechanisms, which may be unmasked in the first few weeks of IP therapy. Bowel injury (fistulas, accidental perforation by the catheter) can also occur, but is uncommon (3 to 5 percent of cases) [20].

CATHETER REMOVAL — The catheter should be removed as soon as all of the courses of chemotherapy have been completed given the high rate of complications [20,32]. Removal can be performed as an office procedure under local anesthesia. The incision is opened, the capsule of scar surrounding the port is cut with a scalpel, and the four sutures are identified, cut, and removed. The port and catheter are pulled out, usually without difficulty, as they do not typically form adhesions to bowel or intraperitoneal structures unless a Dacron cuff was utilized [33-35].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ovarian, fallopian tube, and peritoneal cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Ovarian cancer diagnosis and staging (Beyond the Basics)" and "Patient education: Treatment of ovarian cancer (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Patient selection – In women with optimally cytoreduced (to <1.0 cm) stage III epithelial ovarian cancer, intraperitoneal (IP) administration of platinum and taxane-based chemotherapy has been associated with a survival advantage over intravenous (IV) therapy. (See 'Patient selection' above.)

●Contraindications – Contraindications to IP chemotherapy include being a poor candidate for cytoreductive surgery, active peritonitis or sepsis, extensive abdominal adhesions, and inadequate renal function to allow for cisplatin clearance. (See 'Contraindications' above.)

●Technical considerations – In most cases, the IP port and catheter can be placed at the time of initial surgery, although delayed placement is preferred if there is diagnostic uncertainty, intraoperative issues that preclude safe placement at initial surgery, or if the primary cytoreductive procedure is complicated by gross fecal contamination of the peritoneal cavity. (See 'Procedure' above.)

In patients undergoing debulking surgery that includes bowel resection, we place an IP port at the time of the debulking surgery. In this scenario, we prefer to give the first cycle of chemotherapy IV and start the IV/IP regimen with the second cycle. (See 'Patients undergoing bowel resection' above.)

We utilize a single-lumen implanted port with a 14.3 French (Fr) silicone peritoneal catheter or a fully implantable port attached to a single-lumen venous silicone catheter of large size (9.6 Fr or higher) so that it does not kink and obstruct flow. (See 'IP catheter and port' above.)

●Complications – Treatment-related complications, including abdominal discomfort, infection, obstruction, leakage, access problems, and bowel injury, occur in 10 to 35 percent of patients, but IP therapy can be completed in many. (See 'Complications' above.)

Replacement of a malfunctioning port will allow approximately 50 percent of patients to complete their planned IP therapy. Among the indications for removal of the port and catheter are intraabdominal infection, bowel injury, and non-remediable catheter blockage (such as retrograde flow of dye into the port pocket or at the point where the catheter perforates the peritoneum). (See 'Catheter-related' above.)

Potential complications of IP chemotherapy include neurotoxicity or nephrotoxicity secondary to the chemotherapeutic agents themselves, abdominal pain related to intraperitoneal infusion of fluid, or catheter-related problems including blockage, leakage of infusate, or bowel injury. (See 'Complications' above.)

●Chemotherapy administration – The likelihood of nephrotoxicity can be diminished with IV hydration both before and after IP chemotherapy as well as an antiemetic regimen that addresses both acute and delayed nausea. (See 'Chemotherapy administration' above.)

●Catheter removal – After treatment is completed, the IP catheter is removed as soon as possible. (See 'Catheter removal' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Joan L Walker, MD, who contributed to an earlier version of this topic review.