Complications
Improved survival with intraperitoneal chemotherapy is associated with increased toxicity (e.g., gastrointestinal, renal, metabolic, fatigue, infection, pain) when compared with standard intravenous therapy. This toxicity, however, appears short-term and manageable.[152]
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Because of the significant myelosuppression seen with intraperitoneal therapy, consideration of granulocyte colony-stimulating factor support is warranted.
Intraperitoneal chemotherapy is also associated with catheter-related complications.[253]
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In one study comparing intraperitoneal with intravenous chemotherapy, less than half (42%) of patients completed all 6 cycles of intraperitoneal therapy.[254] Of those who did not complete all 6 treatments, 34% were attributed to catheter complications such as infection, occlusion, or leaking.[254] Of note, the type of intraperitoneal catheter used, and techniques for insertion, were not standardised in this study.
Also called hand-foot syndrome, PPE is a relatively common cutaneous and dose-limiting toxicity with liposomal doxorubicin. Presenting as paraesthesia, with painful redness of the palms and soles, PPE often progresses to skin ulceration. Risk of PPE increases with increasing dose.[255]
Preventative measures include dose reduction, extending the administration interval, avoiding friction and heat to hands and feet (e.g., avoiding hot water, rubbing, impact on hands and feet), and, finally, drug withdrawal.
Topical 99% dimethylsulfoxide (DMSO) is effective when used 4 times a day for 2 weeks. Complete resolution occurs within 1-3 weeks. Corticosteroids have also been used to reduce inflammation. Vitamin B6 has some evidence of symptom reduction. Additional treatments include applying ice packs to affected areas for 15- to 20-minute intervals, to elevate hands and feet, and to apply antibiotic ointment to open sores.[256][257]
A common complication.
Scalp cooling devices may be used to lower the risk of hair loss.[258]
A common complication.
Around 20% of patients undergoing cytoreductive surgery may have minor infections.[234] Urinary tract infections and wound cellulitis are the most common minor types. The risk of surgical complications increases as the length of surgery increases.
A surgical-site infection prevention bundle in women undergoing ovarian cancer operations may reduce infection rates.[234]
Prolonged urinary catheterisation is also a risk factor for urinary tract infection because the catheter serves as a direct portal to infection. Urinary catheterisation is needed, however, to monitor low urine output as a result of extensive third spacing that can occur after debulking surgery.[235]
Treatment with antibiotics based on sensitivities obtained from culture of urine or the wound is appropriate. In order to decrease the infection risk, a first-generation cephalosporin should be administered within a 1-hour window prior to the surgical incision in gynaecological cases (clindamycin plus gentamicin is appropriate for patients with a history of anaphylaxis to penicillin). If colorectal surgery is anticipated, a second-generation cephalosporin is recommended. One randomised controlled trial demonstrated improved efficacy in preventing surgical site infections in elective colorectal surgery with the use of ertapenem when compared with cefotetan.[236]
Around 20% of patients undergoing surgical staging and debulking endure blood loss of >1 L. Given the extensive surgical techniques required for optimal cytoreduction, procedures are often prolonged, resulting in increased blood loss.[235]
No universal haemoglobin threshold exists that serves as a trigger point for transfusion. Therefore, the majority of patients should be transfused based on volume status and indicators of oxygenation.[237] Current guidelines from AABB (formerly the American Association of Blood Banks) favour a restrictive transfusion policy (haemoglobin threshold of 7 or 8 g/dL based upon comorbid conditions of the patient).[238]
Retrospective data indicate that blood transfusion may shorten survival in patients with ovarian cancer, possibly due to the immunosuppressive effects of blood transfusion.[239] Need for blood transfusion must be carefully considered for patients undergoing treatment with curative intent.
Around 10% of patients undergoing surgical staging and debulking have gastrointestinal complications. Prolonged ileus is the most common gastrointestinal complication often resulting in extended hospitalisation. This usually results from extensive manipulation of the small bowel during surgery or the effects of multiple tumour implants along the mesentery of the bowel (carcinomatous ileus).[235]
The diagnosis of a prolonged postoperative ileus can be made clinically or with an abdominal x-ray. Expectant management with conservative measures is the standard of care. This includes keeping the patient nil-by-mouth (NPO), administering intravenous fluids and anti-emetics, and repleting electrolytes.
Patients with copious vomiting may benefit from a nasogastric tube; routine prophylactic use of nasogastric tubes is not supported.[240] If there is no resolution within 48-72 hours, a bowel obstruction must be considered and further imaging and surgical intervention may be necessary.
The initiation of total parenteral nutrition is often recommended after 7-10 days of no oral intake, but whether this improves survival or quality of life is unclear.[241]
Bowel perforation or fistula have been reported in patients with recurrent epithelial ovarian cancer being treated with bevacizumab.[209][259] Patients with heavily pre-treated ovarian cancer or recto-vaginal nodularity may be at increased risk for bowel perforation or fistula.[259][260]
Careful patient selection may reduce risk.
Typically, resolves with cessation of therapy.
Typically, resolves with cessation of therapy.
Around 2% of patients undergoing surgical staging and debulking endure thromboembolic events. According to Medicare data in the US, ovarian cancer is associated with one of the highest rates of deep venous thrombosis (DVT) and pulmonary embolism (PE) when compared with other malignancies.[242] Given the added risk of major abdominal surgery, thromboprophylaxis is of critical importance.[235] Mechanical and medical (heparin or low molecular weight heparin) methods for thromboprophylaxis are recommended.[243]
DVT and non-massive PE can be treated with therapeutic low molecular weight heparin, whereas unstable patients with PE should be treated with intravenous heparin.[244] For prophylaxis, small randomised trials in gynaecological oncology patients have demonstrated similar efficacy of pneumatic compression and low molecular weight heparin in preventing postoperative thrombosis.[231] One large randomised controlled trial compared patients who received subcutaneous enoxaparin for 6-10 days postoperatively to those who received it for 27-31 days after major abdominal surgery for cancer. The extended-treatment group had significantly decreased rates of thrombosis: 4.8% compared with 12%.[245]
The risk of death for patients undergoing debulking surgery is estimated at 1.8%. Increasing age and advanced disease are associated with increased risk of postoperative mortality following primary debulking surgery.[246]
Patients with multiple medical comorbidities and a poor performance status often receive neoadjuvant chemotherapy, thereby reducing the risk of postoperative morbidity and mortality.[247][248][249] In one systematic review of trials of women with advanced epithelial ovarian cancer, there was little or no difference in survival outcomes between neoadjuvant chemotherapy followed by interval debulking surgery compared with primary debulking surgery plus chemotherapy. However, postoperative mortality and serious adverse events may be reduced in those receiving neoadjuvant chemotherapy.[92][160]
While neutropenic sepsis is a rare complication, it can be life-threatening.
There have been reports of severe hypertension and posterior reversible encephalopathy syndrome (PRES) associated with niraparib, with some cases occurring within the first month of treatment.[177]
Niraparib should be discontinued if hypertensive crisis occurs or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, and if PRES is suspected or confirmed.
A common final pathway of ovarian cancer is a small-bowel obstruction resulting from disease progression. Typically, this occurs late in the disease process and often portends a fatal outcome. The obstruction is usually multi-focal owing to the presence of diffuse carcinomatosis, as opposed to one mass lesion causing obstruction. Bowel rest is the cornerstone of treatment.
Decompression of the gastrointestinal tract with a nasogastric tube, in addition to electrolyte repletion, often improves symptoms. For cases where the bowel obstruction is likely to be chronic, a gastrostomy tube is appropriate. Surgical intervention is associated with significant morbidity, but can palliate symptoms in select patients.[250]
A common dose-limiting complication and the most common toxicity related to etoposide. Thrombocytopenia is the specific dose-limiting toxicity for carboplatin. Ototoxicity and nephrotoxicity are the dose-limiting toxicities for cisplatin.
The development of ascites at the time of diagnosis of advanced-stage disease is common and usually resolves with the initiation of chemotherapy.
The development of ascites following disease recurrence can cause symptoms of nausea and emesis, bloating, early satiety, dyspnoea, and pain. Treatment of recurrent ascites is palliative in nature. Large-volume paracentesis is one option, but carries the risks of infection and visceral injury. Furthermore, the effects of paracentesis are often short-lived, with symptoms recurring over 1-2 weeks post-treatment. Ideally, if a therapeutic response to second-line therapy occurs, the ascites will resolve.
In patients with treatment-resistant disease, the chance of an ascites treatment response is low. Bevacizumab has shown some promise in treating this difficult problem.[251] In addition, an implantable drainage catheter can also be placed for palliative purposes.
Paclitaxel and cisplatin are associated with the development of peripheral neuropathy that often persists after the cessation of treatment. With paclitaxel given over 3 hours, peripheral neuropathy may occur, limiting treatment. Combination paclitaxel plus carboplatin is associated with a stocking-glove distribution. Other causative agents are gemcitabine, topotecan, etoposide, bevacizumab, and liposomal doxorubicin. Currently, there is no preventative strategy for this complication, which can significantly impact a patient's quality of life. This complication was the most common reason for therapy discontinuation in one phase 2 trial of the Gynecologic Oncology Group (GOG).[252]
Dose-limiting toxicity may occur 5-10 days after starting medication. Ulceration may result, which may lead to severe infections. Clinicians should consider lowering the dose or discontinuing.
In patients treated for a prolonged time with etoposide, there is a risk of developing a secondary malignancy, specifically acute myeloid leukaemia.
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