Peritoneal Cancer

The peritoneum is a serous lining of mesothelial cells with a rich vascular and lymphatic capillary network that covers the abdominal and pelvic walls and organs. Peritoneal neoplasia can originate de novo from the peritoneal tissues (primary) or invade or metastasize into the peritoneum from adjacent or remote organs (secondary).

A number of primary cancers have been described to originate from the peritoneum, some of which have been implicated in many cases of carcinomas of unknown primary origin. Ovarian cancer arising in women several years after bilateral oophorectomy is believed to be one of these primary peritoneal cancers. Other described primary peritoneal cancers and tumors include malignant mesothelioma, benign papillary mesothelioma, desmoplastic small round cell tumors, peritoneal angiosarcoma, leiomyomatosis peritonealis disseminata (LPD), and peritoneal hemangiomatosis.

The peritoneal cavity, enclosed by visceral and parietal peritonea, is the largest potential space in the body. Any pathologic process involving the peritoneal cavity can easily disseminate throughout this space by means of unrestricted movement of fluid and cells.

Primary malignant diseases arising from the peritoneal cavity include malignant mesothelioma, cystic mesothelioma, primary peritoneal carcinoma, and desmoplastic small round cell tumor.

Malignant mesothelioma

Malignant peritoneal mesothelioma is a rare but aggressive tumor derived from the peritoneal mesothelium. Although most mesotheliomas involve the pleural surface, 20-30% arise from the peritoneum and are associated with asbestos exposure and abdominal therapeutic radiation. Association of malignant peritoneal mesothelioma and asbestos exposure has been reported to be as high as 83%.

Mesotheliomas are composed of strands of connective tissue covered by cells that react positively to periodic acid-Schiff staining in the cytoplasm. These cells grow in multiple layers, forming papillary or tubular formations. Histologically, malignant mesothelioma is classified into epithelial, sarcomatoid, and mixed. Clinical features of malignant mesothelioma include abdominal pain, abdominal or pelvic masses, and thrombocytosis; ascites is the major factor in the disease morbidity and mortality.[2] Rarely, the tumor spreads into the pleural space.

On CT scan, this neoplasm can appear as peritoneum-based masses or abdominal ascites with associated nodular or diffuse peritoneal thickening.

This locally aggressive disease is difficult to treat or palliate. Commonly, treatment regimens combine aggressive cytoreductive surgery with intraperitoneal chemotherapy. Thorough cytoreductive surgery is the cornerstone of current treatment, while hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) is a promising strategy in suitable patients.[3]

Cystic mesothelioma

Cystic mesothelioma is a rare intermediate-grade tumor with a predilection for surfaces of the pelvis.[4] Typically, these lesions consist of multiple grapelike clusters of mesothelium-lined cysts separated by fibrous tissue. The nomenclature for this entity is confusing, and several synonyms (eg, multilocular peritoneal inclusion cyst, cystic mesothelioma) are used interchangeably in the literature.

This rare tumor commonly occurs in young to middle-aged women and typically presents with abdominal pain, tenderness, or distension.

Radiologic tests demonstrate thin-walled cysts containing watery secretions, easily seen on ultrasound, CT scan, and MRI.[5]

Some authors reported effective intraperitoneal chemotherapy, but no clinical study is available about long-term outcome. The short-term prognosis is favorable, although the tumor recurs in 25–50% of cases.

The differential diagnosis includes lymphangioma, mesenteric-omental cysts, ovarian cystadenoma and cystadenocarcinoma, cystic teratoma, pseudomyxoma peritonei, cystic smooth muscle tumors, visceral cysts, and endometriosis.

Primary peritoneal carcinoma

Primary peritoneal carcinoma (ie, serous surface papillary carcinoma) arises primarily from peritoneal cells. The mesothelium of the peritoneum and the germinal epithelium of the ovary arise from the same embryologic origin; therefore, the peritoneum may retain the multipotentiality allowing the development of a primary carcinoma.

This rare malignancy predominantly affects postmenopausal women and typically displays multicentric peritoneal and omental involvement. Pathologically and clinically, it resembles papillary serous ovarian carcinoma. This malignancy is differentiated from its ovarian counterpart by the fact that it involves the extraovarian peritoneum significantly and the ovarian surface minimally or not at all. Extensive calcification or omental caking is present in many cases and is a useful CT finding to exclude mesothelioma. The absence of an ovarian mass is critical for excluding metastatic papillary serous ovarian carcinoma, which otherwise has a similar CT appearance.

Treatment of this malignancy is very similar to that of epithelial ovarian cancer, which includes combination chemotherapy after optimal cytoreductive surgery.

Desmoplastic small round cell tumor

This tumor is a highly aggressive malignancy that has recently been described. It involves the peritoneal cavity in most cases. Unlike the other primary peritoneal neoplasms, desmoplastic small round cell tumor (DSRCT) most often affects young adults. This malignancy extensively and rapidly invades the peritoneal surfaces with hematogenous metastasis to the liver, lungs, and lymph nodes.

Cytologically, DSRCT is a highly cellular tumor composed of small round cells with granular chromatin, nuclear molding, and inconspicuous nucleoli that are arranged singly and in clusters.[6] This tumor exhibits a unique immunohistochemical profile, characterized by coexpression of epithelial (keratin and epithelial membrane antigen), neural (neuron-specific enolase and CD56), mesenchymal (vimentin), and myogenic (desmin) markers. The reciprocal chromosomal translocation t (11; 22)(p13; q12) is also specific for DSRCT.

Radiologic investigation shows multiple rounded peritoneal masses with or without ascites. The omentum and paravesical regions are often involved.

The recommended treatment is a combination of multiagent chemotherapy with adjuvant surgery and radiation. The overall survival for people with this disease is poor despite aggressive treatment.

Other neoplasms

Although clear cell carcinoma is often derived from the ovary and associated with endometriosis, cases of peritoneal origin have been reported. Residual tumor volume appears to determine survival in these patients. These tumors are typically resistant to conventional platinum-based chemotherapy but in one case, adjuvant chemotherapy using irinotecan and cisplatin was effective.[7]

In addition to the above-mentioned primary peritoneal malignancies arising from the peritoneal lining, various types of neoplasms may develop from mesenchymal and lymphatic tissues of the abdominal and pelvic cavities. This includes different forms of sarcomas, histiocytoma,[8] gastrointestinal stromal tumors (GIST), and lymphoproliferative malignancies. Moreover, the differential of peritoneal malignancies includes many benign tumors derived from lymphatic, vascular, neuromuscular, or fatty tissues.

A chromosomal translocation, which results in the fusion of the Ewing sarcoma gene with the Wilms tumor gene, has been identified and implicated in desmoplastic small round cell tumors.

Hereditary predisposition may play a role in primary peritoneal carcinoma; patients with the BRCA1/2 mutations have an increased risk.[9]

Susceptibility to mesothelioma may be influenced by genetic makeup.[10]  Although conventional wisdom dictates that asbestos is the environmental factor most commonly associated with mesothelioma, asbestos does not transform human mesothelial cells in tissue culture. This suggests that additional carcinogens act in concert with asbestos to cause mesothelioma. Simian virus 40 has been proposed as an etiologic agent; however, the evidence for this hypothesis is weakening.[10]

All of the peritoneal cancers are rare, with an age-adjusted incidence of 0.65 per 100,000 women in the United States. Primary peritoneal carcinoma is very uncommon. The malignant peritoneal mesothelioma is approximately 10 to 15 percent of all cases of mesothelioma in the United States and approximately 600 new cases are diagnosed every year. 

Primary peritoneal carcinoma is a rare tumor that occurs almost exclusively in women. Malignant mesotheliomas show extreme male predominance (93% in one series). Desmoplastic small round cell tumors occur in adolescent persons and young men. Although primary peritoneal carcinoma has been reported to occur in older patients than do epithelial ovarian cancers, a United Kingdom study found no statistical difference between the two groups with regard to age (mean 64.43 vs 64.07 years, respectively P= 0.9).[11]  Benign cystic peritoneal mesotheliomas are rare and are found predominantly in younger women.

Most cases of leiomyomatosis peritonealis disseminata have been discovered in reproductive-aged women (mean age 37 y), in young pregnant women, and in women who have hormonal excess for any other reason. In most reported cases, nodules either regress or exhibit growth once the hormonal stimulation has been removed.

Peritoneal cancers traditionally have been associated with significant morbidity and universal mortality, however, significantly improved long-term survival has been reported in patients with resectable disease and complete cytoreduction.[12]

Survival is poor for patients with primary peritoneal carcinoma, with 100% mortality; the median survival reported is 12-25 months, even with extensive surgery and chemotherapy. Benign cystic peritoneal mesotheliomas are associated with prolonged survival despite bulky disease. Desmoplastic small round cell tumors are associated with a reported median survival of 17 months.

In a multi-institutional data registry that included 405 patients with diffuse malignant peritoneal mesothelioma, overall median survival was 53 months (1 to 235 months), and the 5-year survival rate was 47%. Multivariate analysis showed that the following four prognostic factors were independently associated with improved survival[13] :

• Epithelial subtype (P <  0.001)
• Absence of lymph node metastasis (P <  0.001)
• Completeness of cytoreduction (CC) scores of CC-0 or CC-1 (P <  0.001)
• Use of hyperthermic intraperitoneal chemotherapy (P = 0.002)

Peritoneal tumors usually do not cause symptoms in the early stages of the diseases. The advanced stages usually present as abdominal fullness after eating, abdominal distention, and diffuse abdominal pain secondary to ascites. This tumor is described almost exclusively in women. Atypical presentations of primary peritoneal carcinoma have been described, including a case of severe glandular dysplasia on a screening Papanicolaou test (Pap smear).

Patients with malignant peritoneal mesothelioma usually present with symptoms and signs of advanced disease, including pain, ascites, weight loss, or an abdominal mass. Diffuse involvement of the peritoneal cavity is typical, often including omental caking and diaphragmatic and pelvic tumor deposits. The clinical presentation of primary peritoneal cancer is often typical of advanced ovarian cancer, with elevated serum level of cancer antigen 125 (CA125).

Thrombocytosis is common and is associated with a poor prognosis. Other common clotting abnormalities include phlebitis, emboli, hemolytic anemia, and disseminated intravascular coagulation.

Esophageal achalasia, secondary amyloidosis, and dermatomyositis have been reported.

Most patients die without metastasis or involvement of the chest.

Desmoplastic small round cell tumors occur typically in young patients and manifest with extensive involvement of the peritoneal surfaces. Rapid multifocal growth and hematogenous metastasis to the liver, lungs, and lymph nodes are common.

Leiomyomatosis peritonealis disseminata is found most commonly in women of reproductive age, often during pregnancy. These patients are usually asymptomatic, have a long-term history of oral contraceptive use, or have uterine leiomyomas at the time of diagnosis. Almost all cases of this disease have been discovered intraoperatively during obstetric and gynecologic surgical procedures.[14, 15]

Peritoneal hemangiomas are usually associated with hemangiomas of the GI tract. They are rare and can manifest as ascites, anemia (from chronic blood loss), thrombocytopenia, and coagulopathy.

Complications of peritoneal tumors include the following:

• Small Bowel obstruction 
•  Urinary tract obstruction secondary of blockage of the ureters by tumor
•  Shortness of breath due to malignant pleural effusion

Rarely, a paraneoplastic syndrome may develop during the course of the disease. Features may include any of the following:

• Cerebellar degeneration
• Polyneuritis
• Dermatomyositis
• Hemolytic anemia
• Disseminated intravascular coagulation
• Acanthosis
• Nephrotic syndrome

In malignant peritoneal mesothelioma, findings from cytologic examination of ascites can suggest the diagnosis, and findings from percutaneous biopsy of the omentum can help verify the diagnosis. This condition is usually confined to the abdomen at the time of diagnosis.

Standard imaging tests, including ultrasonography and helical computed tomography (CT) scans, are notably insensitive for the detection of peritoneal tumors. CT is limited in detecting small peritoneal metastases. CT can depict tumors larger than 1 cm with sensitivity of 85–93% and specificity of 91–96%, but the sensitivity decreases to 25–50% in detecting implants that are 1 cm or smaller.[19]

Ultrasonography is similarly insensitive; rather than relying on solid tumor detection, therefore, it is important to consider findings that may suggest the presence of peritoneal lesions. These include the presence of ascites, fixing together of bowel loops, thickening of mesentery, and omental matting.

CT scan findings are nonspecific in primary papillary serous carcinoma of the peritoneum. Consider this diagnosis when findings include the following:

• Ascites
• Omental caking
• Diffuse enhancement with nodular thickening of the parietal peritoneum of the pelvis
• Normal-sized ovaries, with or without a fine enhancing surface nodularity of the ovary.

Malignant peritoneal mesotheliomas produce CT findings that range from peritoneum-based masses (a so-called "dry" appearance) to ascites, irregular or nodular peritoneal thickening, and an omental mass (a so-called "wet" appearance). Scalloping of the peritoneum or direct invasion of adjacent abdominal organs may also be seen.[1]

Some studies show that magnetic resonance imaging (MRI) is superior to helical CT scan for the detection of peritoneal and bowel wall abnormalities.

Preoperative imaging of the abdomen and pelvis plays an important role in determining the extent of peritoneal disease in patients who are being considered for cytoreductive surgery. Delayed gadolinium-enhanced imaging combined with diffusion-weighted MRI has been shown to be a superior imaging modality to predict which patients will be able to undergo complete primary cytoreductive surgery. In one study, MRI more accurately predicted peritoneal cancer index (PCI) preoperatively in patients undergoing evaluation for cytoreductive surgery than CT. PCI measures the size and extent of peritoneal tumor at laparotomy.  For predicting resectability, MRI had sensitivity of 95%, specificity of 70%, and accuracy of 88% compared with 55%, 86%, and 63%, respectively, for CT.[20]

Positron emission tomography (PET) imaging has not been shown to be sensitive for lesions smaller than 1 cm in the abdominal cavity.

Dual-time point imaging after carbonated water may increase the accuracy of 18F-fluorodeoxyglucose (FDG) PET/CT for the imaging of peritoneal cancer in patients affected by colorectal cancer.[21]

Findings from radionuclide scan studies can help confirm the diagnosis of peritoneal hemangiomas; the isotope concentrates in the area where platelets are being sequestered. A CT scan and ultrasound also may detect larger hemangiomas. Angiographic evaluation is a more precise, although invasive, procedure that may be considered when radionuclide scans, CT scan, and ultrasound findings are negative.

The workup of peritoneal lesions includes peritoneal lavage cytology. Peritoneal lavage can be performed using a percutaneous closed technique or at the time of laparoscopy or laparotomy. The sensitivity of the test results depends on the ability to completely lavage all regions of the peritoneal cavity and the ability to detect cancer cells being shed into the peritoneal cavity by the tumor.

Direct visualization of the peritoneal surfaces along with palpation of the abdominal contents is by far the most sensitive modality for detecting peritoneal cancer. This can be accomplished with a minimally invasive approach (ie, laparoscopy), which allows for safe, directed peritoneal lavage for cytology, or with open abdominal exploration and palpation of the peritoneal surfaces. Open abdominal exploration and palpation are extremely sensitive for 1- to 2-mm peritoneal nodules.

Primary peritoneal carcinoma is histologically indistinguishable from primary epithelial ovarian carcinoma; however, primary ovarian cancer can be excluded when the following criteria are present:

• Both ovaries are of normal size
• The extraovarian involvement is greater than the involvement on the surface of the ovary
• The ovarian component is smaller than 5 × 5 mm within the ovary or confined to the ovarian surface
• Cytologic characteristics are of the serous type.

 The decision to proceed with surgery depends on the symptoms, elevation of tumor markers, and imaging findings specific for peritoneal cancer. One should have high suspicion for peritoneal mesothelioma in any individual with evidence of a diffuse malignant process in the abdomen on imaging. Multimodality therapy is currently the most commonly accepted therapeutic approach to peritoneal mesothelioma.

For patients without extraperitoneal spread of diffuse malignant peritoneal mesothelioma who have a good performance status, cytoreduction surgery (CRS) and hyperthermic intraoperative peritoneal perfusion with chemotherapy is recommended. This includes using the combination of surgical cytoreduction, intraperitoneal perioperative chemotherapy, and hyperthermia.

Intraperitoneal chemotherapy greatly enhances drug concentrations in the peritoneal cavity and decreases its systemic toxicity. See the videos below.

First-line chemotherapy for peritoneal cancer is a platinum agent with a taxane. A 2006 multiple-treatment meta-analysis that included 60 trials in women showed that a platinum-taxane combination improved survival when compared with taxane. If patients are found to have breast cancer susceptibility gene 1 or 2 (BRCA1/2)) mutations (BRCA carriers), olaparib maintenance therapy is recommended. 

In addition to the intraoperative use of heated chemotherapeutic drugs such as cisplatin, mitomycin, or doxorubicin, newer techniques include adding immunotherapeutic agents such as interleukins and interferons. While the median survival with traditional therapeutic options ranges from 4 to 12 months, the application of multimodality therapy has shown promising results with increased survival approaching 60 months.[22]

For patients with unresectable or recurrent malignant mesothelioma, palliative systemic chemotherapy (with different regimens such as cisplatin plus pemetrexed) should be considered. Other antineoplastic agents that may be used include cisplatin plus paclitaxel or mitomycin, doxorubicin, and irinotecan. Preclinical trails have shown a possible role of phosphatidylinositol-3-kinase (P13K) in peritoneal mesothelioma, and P13K inhibitors are a potential therapy. In 2017, the FDA approved pembrolizumab, a programmed death 1 (PD-1) inhibitor, for patients with mesothelioma that is refractory to other treatment options.

Primary peritoneal carcinoma is treated similarly to ovarian cancer, with cytoreduction and chemotherapy. Multimodality treatment consisting of tumor debulking followed by chemotherapy regimens based on 5-fluorouracil, doxorubicin, or cisplatin has been shown to have high response rate and improvement of median survival. Furthermore, the use of newer antineoplastic agents such as taxanes, topoisomerase I inhibitors, gemcitabine, and vinorelbine, alone or in combinations (eg, gemcitabine/cisplatin, irinotecan/cisplatin, docetaxel/gemcitabine, gemcitabine/carboplatin) has increased median survival to 8-11 months. In addition to chemotherapeutic agents, antiangiogenic drugs such as bevacizumab and erlotinib have shown some benefit.

In 2014, the FDA approved bevacizumab (Avastin) for platinum-resistant, recurrent, epithelial ovarian cancer in patients who received no more than two prior chemotherapy regimens. It is indicated for use in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan.[23] In 2016, bevacizumab’s indication was expanded to include treatment of platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with carboplatin and either paclitaxel or gemcitabine, followed by bevacizumab alone.[24, 25]

It is generally accepted that all patients with good performance status should be considered for a trial of empiric chemotherapy, preferably with a regimen containing newer drugs. The combination of paclitaxel and carboplatin is a reasonable first-line therapy with the addition of a third agent (etoposide or gemcitabine) providing possible benefit. Supportive measures should be considered in patients with poor performance status.

Secondary peritoneal carcinomatosis of unknown primary site usually responds to chemotherapy regimens that are effective in the treatment of advanced epithelial ovarian cancer. 

Treatment of primary peritoneal carcinoma consists of total abdominal hysterectomy and bilateral salpingo-oophorectomy as needed, with debulking of tumor and follow-up chemotherapy. 

Cytoreductive surgery (CRS) is the removal of macroscopic peritoneal tumors. It may involve multiple peritonectomy and visceral resection procedures. Electrosurgery is used to limit bleeding from the vascular peritoneal surface.[12]

Treatment of malignant peritoneal mesothelioma consists primarily of surgical palliation. Complete surgical resection is rarely, if ever, feasible and has not been shown to afford a survival benefit in the absence of additional therapy. If laparoscopy is used to help make the initial diagnosis, confine port sites to the abdominal midline because port site recurrence has been described, requiring extensive abdominal wall resection.[26]

Benign cystic mesothelioma tends to recur even with aggressive surgical removal; however, among recorded cases, no deaths have been attributable to this disorder.

In patients with desmoplastic small cell tumors, the combination of aggressive surgical debulking and systemic chemotherapy with cyclophosphamide, doxorubicin, and vincristine interspersed with ifosfamide, etoposide, and mesna (P6 protocol) appears to lead to an improved outcome. However, surgical excision is recommended only for nonmetastatic disease.[27]

Treatment of peritoneal and GI hemangiomas has involved surgical removal.

Patients strongly suspected to have peritoneal carcinoma should be referred to a gynecologic oncologist. 

Follow up to evaluate patients for complications of the cancer, spread of the cancer, and possible complications of therapy. Screening for known associated cancers and cancer syndromes is essential.

The Enhanced Recovery After Surgery Society (ERAS) has published clinical practice guidelines on perioperative care in cytoreductive surgery for peritoneal malignancy.[28]  ERAS notes that cytoreductive surgery, with or without the addition of hyperthermic intraperitoneal chemotherapy, (CRS ± HIPEC) has become a treatment standard for peritoneal surface malignancies. However, these extended procedures may cause excessive tissue trauma with subsequent inflammation that ultimately lead to potentially life-threatening adverse effects. Major complication rates have been reported to be as high as 51%. ERAS recommendations include the following:

• Advanced resuscitation and dedicated care protocols are warranted. Early reversal of this pathophysiologic cascade by improvements of perioperative care forms the basis of ERAS interventions.
• Prophylactic nasogastric drainage for CRS ± HIPEC, in the absence of risk factors for delayed gastric emptying (resection of lesser omentum), should not be done because nasogastric decompression has been associated with undesired effects of delayed resumption of gastrointestinal motility and increased postoperative complications.
• Removal of a urinary catheter as early as the morning of postoperative day 3 is recommended.
• Thoracic epidural analgesia (TEA: T5-11) containing local anesthetics and short-acting opiates is recommended for 72 hr after CRS ± HIPEC to prevent postoperative ileus, and for at least 72 h afterward as an alternative to intravenous opiates for postoperative analgesia.
• After TEA removal, analgesia with paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids is recommended.
• Early oral intake resumption after CRS ± HIPEC, aiming for clear liquids on the day of surgery and solid food from postoperative day 1, in the absence of risk factors for delayed gastric emptying (resection of lesser omentum), is recommended to improve mortality, anastomotic dehiscence, resumption of bowel function, and hospital length of stay.
• Daily recording of nutritional intake after CRS ± HIPEC to identify patients with insufficient intake is recommended routinely.
• Preemptive parenteral nutrition after CRS ± HIPEC (in addition to oral and/or enteral nutrition), for 7 postoperative days is recommended in selected patients (expected insufficient oral/enteral intake).
• Monitoring of blood glucose in critically ill patients after CRS ± HIPEC and correction of glycemia using short-acting insulin to keep blood glucose levels at 140–180 mg/dL (7.8–10 mmol/L) are recommended routinely to reduce postoperative mortality.
• Mechanical thromboprophylaxis (intermittent pneumatic compression) until complete mobilization, in association with pharmacologic thromboprophylaxis as an alternative to pharmacologic thromboprophylaxis alone, should be performed routinely.
• Pharmacologic thromboprophylaxis (low molecular weight heparin, unfractionated heparin or fondaparinux) started 12 hr before CRS ± HIPEC should be performed routinely.
• Extended pharmacologic thromboprophylaxis until 4 weeks after CRS ± HIPEC, as an option in addition to in-hospital thromboprophylaxis, should be performed routinely to reduce the risk of asymptomatic deep vein thrombosis (not pulmonary embolism).
• Bevacizumab or other anti-angiogenic treatment should be routinely discontinued at least 5 weeks before CRS ± HIPEC to reduce intraoperative bleeding complications.
• Placement of ureteral stents to reduce the risk of ureteral complications in patients with a high probability of pelvic peritonectomy should not be done routinely
• Intraoperative administration of loop diuretics and dopamine for renal protection should not be performed routinely in patients undergoing CRS and HIPEC.
• Mobilization and physiotherapy as early as the day of surgery (out of bed) with goals of > 2 hr of physical exercises for postoperative day 2 and > 6 hr thereafter should be performed routinely after CRS ± HIPEC to improve capacity to perform out-of-bed activities, facilitate resumption of gastrointestinal function, and decrease postoperative complications.

The goals of pharmacotherapy are to induce remission, to prevent complications, and to reduce morbidity. The current approach favors intraoperative use of heated chemotherapeutic drugs. Both chemotherapeutic and antiangiogenic agents are used.

Class Summary

These drugs inhibit cell growth and proliferation.

Cisplatin (Platinol)

Inhibits DNA synthesis and thus cell proliferation by causing DNA cross-links and denaturation of double helix.

Doxorubicin (Adriamycin, Rubex)

Inhibits topoisomerase II and produces free radicals, which may cause the destruction of DNA. Combination of these events can, in turn, inhibit the growth of neoplastic cells.

Carboplatin (Paraplatin)

Analog of cisplatin. Has same efficacy as cisplatin but with better toxicity profile.

Dose is based on following formula:

Total dose (mg) = (target AUC) X (GFR = 25), where AUC (area under plasma concentration-time curve) is expressed in mg/mL/min and GFR (glomerular filtration rate) is expressed in mL/min.

Cyclophosphamide (Neosar, Cytoxan)

Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Paclitaxel (Taxol)

Mechanisms of action are tubulin polymerization and microtubule stabilization.

Bevacizumab (Avastin)

Bevacizumab is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF) receptors. Blocking the angiogenic VEGF receptor, in turn inhibits tumor angiogenesis, starving tumor of blood and nutrients. It is indicated in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for platinum-resistant recurrent epithelial ovarian cancer in patients who received no more than 2 prior chemotherapy regimens. It is also indicated for women with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine chemotherapy, followed by bevacizumab alone.