Herpes Zoster (Shingles) and Postherpetic Neuralgia Management

Ovarian Cancer:
One of the Common Gynecologic Malignancies

Release Date:  October 1, 2009

Expiration Date: October 31, 2011

FACULTY:

Amy M. Pick, PharmD, BCOP
Assistant Professor of Pharmacy Practice
School of Pharmacy and Health Professions
Creighton University, Omaha, Nebraska

Edward M. DeSimone II, RPh, PhD, FAPhA
Professor of Pharmacy Sciences
School of Pharmacy and Health Professions
Creighton University, Omaha, Nebraska

FACULTY DISCLOSURE STATEMENTS:

Drs. Pick and DeSimone have no actual or potential conflicts of interest in relation to this activity.

U.S. Pharmacist does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacists

acpePostgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
UAN: 0430-0000-09-024-H01-P; 0430-0000-09-024-H01-T
Credits: 2.0 hours (0.20 ceu)

Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists and pharmacy technicians. Estimated time to complete this activity is 120 minutes.

Exam processing and other inquiries to:
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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

GOAL:

To provide information to pharmacists regarding ovarian cancer and its treatment.

OBJECTIVES: 

After completing this activity, the participant should be able to:

  1. Discuss the screening, signs and symptoms, and clinical aspects of ovarian cancer.*
  2. Describe the pharmacologic management of ovarian cancer.*
  3. Discuss the appropriate regimen for preventing or treating nausea and vomiting related to chemotherapy for ovarian cancer.
  4. Explain survival outcomes for the various stages of ovarian cancer.*

*Also applies to pharmacy technicians.


Ovarian cancer is one of the most common malignancies, but it is rarely spoken about. Historically considered a “silent” cancer because most patients present with late-stage disease, ovarian cancer is now recognized to cause symptoms such as abdominal pain and bloating in many women, even in the early stage. Survival depends upon the stage of the disease at presentation. Early-stage ovarian cancer is curable by surgery and chemotherapy; late-stage disease is treated mainly with chemotherapy, but is largely incurable. Because of the high mortality associated with late-stage ovarian cancer, an effective screening method is desperately needed. Pharmacists can play an integral role in the treatment of ovarian cancer by understanding intraperitoneal (IP) chemotherapy, knowing how to manage the hypersensitivity reactions caused by chemotherapy agents, and providing appropriate supportive-care options.

EPIDEMIOLOGY

Ovarian cancer is one of the most common gynecologic malignancies, accounting for approximately 21,650 new cancer cases in 2008.1 Ovarian cancer is also the fifth leading cause of death in women in the United States. It is estimated that a woman’s risk of developing ovarian cancer in her lifetime is 1.7%.2 Most patients are diagnosed after menopause, with a median age of 63 years at diagnosis.3 Ovarian cancer is more common in Western Europe and North America; its incidence is lowest in Japan and in undeveloped countries.4

RISK FACTORS

Risk factors for ovarian cancer include reproductive, genetic, and some environmental factors that are poorly understood. Nonhereditary ovarian cancer, which accounts for 90% to 95% of all cases of ovarian cancer, is likely due to environmental and hormonal factors.4 One risk factor for nonhereditary ovarian cancer is an increased number of ovulatory cycles due to nulliparity (not having given birth to a child) and/or late menopause. Nulliparity is one of the most consistent findings associated with ovarian cancer; compared with a woman who remains nulliparous, risk decreases by 40% after a woman gives birth to her first child. Increasing parity (number of children born) affords additional protection against ovarian cancer.4 The association between late age at menopause and increased risk of ovarian cancer is weakly supported by studies.4 Although an association between ovarian cancer and early menarche (menstruation) would be intuitive, studies have not shown a statistically significant risk.4

There are several medications and surgical procedures that alter the risk of ovarian cancer. One of the best-recognized factors to reduce risk is prolonged use of oral contraceptives (OCs). Studies have found that use of OCs for at least 5 years may decrease the risk of ovarian cancer by more than 50%.5 This finding supports the idea that decreasing the number of ovulatory cycles is key to reducing ovarian cancer risk. Other risk-reduction factors are tubal ligation and hysterectomy.4 Controversy in terms of ovarian cancer risk surrounds prolonged use of ovulation-stimulating hormones (e.g., clomiphene) for fertility enhancement and hormone replacement therapy (e,g., conjugated estrogens); recent evidence, however, suggests that these treatments may have a negligible effect on risk.5,6

Hereditary ovarian cancer accounts for 5% to 10% of all ovarian cancers.5 The most important risk factor for developing ovarian cancer is a family history involving a first-degree relative. Studies suggest a 5% to 7% increased risk when a woman has one or more first-degree relatives with ovarian cancer.5 Distinct hereditary patterns have been identified, such as a patient having ovarian cancer alone; ovarian plus breast cancer; or ovarian plus colon cancer. These patterns can be linked to specific syndromes or genetic disorders. Genetic mutations of BRCA-1 and BRCA-2 have been shown to increase the risk of ovarian cancer, as well as breast cancer. Hereditary nonpolyposis colorectal cancer (also known as Lynch syndrome) also has been linked to ovarian cancer.5

ETIOLOGY

There are three cell lines from which ovarian cancer can arise. Epithelial tumors are the most common, accounting for 80% to 90% of cases; germ cell tumors and stromal cell tumors constitute the rest.2 This paper focuses on epithelial ovarian cancer. Like breast tissue, ovarian cells express several receptors, including estrogen and progesterone.5 Estrogen is involved in cell proliferation, and progesterone antagonizes estrogen by regulating the cell cycle. The varying ratios and doses of estrogen and progesterone in the body are involved in the pathogenesis of ovarian cancer.5 Once an ovarian malignancy arises, it disseminates into the peritoneal cavity and then through the lymphatic system. Studies suggest that lymph node involvement occurs early, with approximately 25% of patients with stage I ovarian cancer having positive lymph node involvement.7

Epithelial ovarian cancer can be further classified by histologic subtypes as well as by tumor grade. Tumor grading is an important prognostic factor in ovarian cancer.8 Epithelial ovarian cancer is graded from 1 to 3, with grade 1 being well differentiated and grade 3 being poorly differentiated. As with other cancers, poorly differentiated tumors have the worst prognosis.9

SYMPTOMS

The view of ovarian cancer as a silent killer of women is misleading. While it is true that more than 70% of patients present with late-stage disease, this is not due to an absence of symptoms.10 Approximately 95% of women with ovarian cancer have recognizable symptoms, but are misdiagnosed. Upon initial presentation, these patients frequently are treated for other diseases, such as depression, irritable bowel syndrome, or constipation, with the practitioner often not considering cancer.11 In 2007, the Gynecologic Cancer Foundation issued a statement on ovarian cancer symptoms. TABLE 1 lists the symptoms more frequently reported by women with ovarian cancer compared with the general population. Health care providers must consider ovarian cancer when patients, especially postmenopausal ones, present with these symptoms. It is to be hoped that increased recognition of the symptoms of ovarian cancer will lead to earlier diagnosis and improved survival.

Table 1
Early Symptoms of Ovarian Cancer

A patient should be advised to see her gynecologist or other health care provider if she experiences the following symptoms daily for more than 2 weeks:

  • Bloating
  • Abdominal or pelvic pain
  • Difficulty eating or early satiety
  • Urinary urgency or frequency
Source: References 10, 11.

SCREENING AND PREVENTION

The need for an effective screening method for ovarian cancer is urgent, since currently none exists. Because the majority of patients are diagnosed with late-stage ovarian cancer and have poor outcomes, research is directed at identifying patients with early-stage ovarian cancer, in the hope of affecting survival. Screening studies have focused on cancer antigen 125 (CA-125) and ultrasound as two methods of early detection.

CA-125, the best-studied biomarker in ovarian cancer, is found on ovarian cells.12 Its normal range is less than 35 U/mL. CA-125 is elevated in more than half of patients with early-stage ovarian cancer. However, CA-125 is not specific for malignancy; it can be elevated in other nonmalignant gynecologic conditions, such as uterine fibroids and endometriosis.2 Studies suggest that, for ovarian cancer, CA-125 is more useful as a monitoring tool for treatment and recurrence.12

Since CA-125 lacks specificity and sensitivity, it has limitations as a single predictive biomarker. Ultrasound is used to detect early ovarian masses, but because this screening tool lacks specificity, numerous surgeries (anywhere from 3-50) are required to detect ovarian cancer in a single patient.13 In ovarian cancer, these screening methods can lead to a large number of false-positives, unwarranted surgeries, and high costs without influencing mortality. Although studies have not shown that routine screening improves survival, there are some women who should undergo surveillance for ovarian cancer. Refer to TABLE 2 for an outline of current surveillance recommendations.

Table 2
Surveillance Recommendations for Ovarian Cancer
Risk Recommendations
Low Risk:
No family history of ovarian cancer
Annual physical and pelvic examination
Moderate Risk:
Family history of ovarian cancer

Starting at age 30-35 y or 10 y younger than earliest diagnosis of ovarian cancer in family
Every 6-12 mo, the following should occur:
  • Transvaginal ultrasound
  • Pelvic examination
  • CA-125 testing
High Risk:
Hereditary ovarian cancer,
BRCA-1– or BRCA-2–positive

Starting at age 25 y or 10 y younger than earliest diagnosis of ovarian cancer in family
Every 6-12 mo, the following should occur:
  • Transvaginal ultrasound
  • Pelvic examination
  • CA-125 testing
CA-125: cancer antigen 125.
Source: References 2, 14.

Patients at high risk for developing ovarian cancer may benefit from chemoprevention or prophylactic surgery. OCs can be used chemopreventively to decrease the risk of ovarian cancer. Current recommendations advise that this option be discussed with women at moderate-to-high risk (family history of hereditary ovarian cancer). Some studies indicate that the use of OCs for 5 years continues to benefit a woman for 15 years after she discontinues therapy.2,14 Some women at high risk may choose prophylactic bilateral salpingo-oophorectomy (removal of the fallopian tubes and ovaries) to reduce their risk. Studies indicate that this surgery can reduce the risk of developing ovarian cancer by 80% to 95% in patients with a known BRCA mutation.14 An added advantage for these patients is that the procedure also decreases premenopausal breast cancer risk by 50%.2,14 One of the biggest challenges of this surgery is correctly selecting the optimal candidate based on age and childbearing status. Many women who develop hereditary ovarian cancer are between 35 and 40 years old. Prophylactic bilateral salpingo-oophorectomy should be discussed with high-risk women after they have completed childbearing.2

DIAGNOSIS AND STAGING

Any patient with signs or symptoms suggestive of ovarian cancer should undergo a more thorough workup. The diagnosis of ovarian cancer often includes imaging studies and pelvic examination. Transvaginal and abdominal ultrasound often is used to locate an ovarian mass.2 If a mass is found, surgical exploration with excision of the mass is performed to ascertain whether the mass is cancerous and, if so, to determine the extent of and appropriately stage the patient’s ovarian cancer.

Two staging systems are used in ovarian cancer: the International Federation of Gynecologic Oncologists (FIGO) nomenclature and the TNM (primary tumor, regional lymph nodes, and distant metastasis) staging system developed by the American Joint Committee on Cancer. The FIGO system is more commonly used for stages I to IV. TABLE 3 gives a brief summary of the FIGO staging system for ovarian cancer.

Table 3
FIGO Staging System for Epithelial Ovarian Cancer
Stage Description 5-Year Survival Dataa
Stage I
Stage IA
Stage IB
Stage IC
Stage II
Stage IIA
Stage IIB
Stage IIC
Stage III

Stage IIIA
Stage IIIB
Stage IIIC
Growth limited to ovaries
Growth limited to one ovary; no tumor on external surface
Growth limited to both ovaries; no tumor on external surface
Stage IA/IB with tumor on external surface
Growth involving one or both ovaries with pelvic disease
Extension and/or metastasis to uterus or fallopian tubes
Extension to other pelvic tissues
Stage IIA/IIB with peritoneal washings or ascites positive for cancer
Tumor involving one or both ovaries with cancer outside pelvis
and/or positive retroperitoneal or inguinal lymph nodes
Microscopic diseaseb in upper abdomen
Diseaseb <2 cm in upper abdomen
Diseaseb >2 cm in upper abdomen or positive retroperitoneal/inguinal lymph nodes
50%-90%



20%-80%



20%-58%




6%-14%
Stage IV Ovarian cancer with distant metastatic disease  
a Range is variable due to grading of tumor. Grade 2–3 tumors have lower survival than grade 1 tumors.
b Ovarian cancer.
FIGO: International Federation of Gynecologic Oncologists.
Source: References 8, 9.

One important thing for the pharmacist to remember is that a patient with presumed ovarian cancer should be referred to a gynecologic oncologist. Unlike medical oncologists, gynecologic oncologists perform the exploratory surgery and do the staging. Numerous studies have found higher survival outcomes when the surgery is performed by a gynecologic oncologist versus a general surgeon. It is theorized that gynecologic oncologists do a more complete cytoreductive surgery and have a better understanding of the importance of complete disease removal in ovarian cancer.2

PROGNOSIS

The prognosis for ovarian cancer is multifactorial. Some positive factors are younger age, lower stage, good tumor differentiation, and good performance status (e.g., Eastern Cooperative Oncology Group classification 0-1).15 Most patients present with advanced disease, which has a low cure rate (20%-30%). Fewer than 30% of patients are diagnosed with early-stage disease, which has a cure rate of 70% to 90%.9 TABLE 3 gives 5-year overall survival data for the specific stages.

TREATMENT

Surgery and chemotherapy are the two main treatment modalities for ovarian cancer. Cytoreductive surgery, which is performed to assess the extent and stage of the disease, often involves total abdominal hysterectomy and bilateral salpingo-oophorectomy.8 If disease is extensive, splenectomy, bowel resection, or radical pelvic dissection may be performed. After surgery, the majority of patients receive systemic chemotherapy. Systemic chemotherapy may be given IV or IP. Radiation is rarely used in patients with ovarian cancer because of limited positive outcomes.16 The following sections discuss the treatment of early-stage and late-stage ovarian cancer, with an emphasis on chemotherapy.

Drug Treatment

Paclitaxel: Paclitaxel prevents the depolymerization of microtubules, which inhibits the cell-cycle process.17 Common side effects of paclitaxel include neutropenia, complete alopecia, peripheral neuropathy, cardiovascular effects (e.g., edema, flushing), and allergic reactions. Cremophor, the vehicle used to solubilize paclitaxel, is known to leach the plasticizer diethylhexyl phthalate (DEHP) from polyvinyl chloride (PVC) bags. For this reason, paclitaxel must be prepared with non-DEHP or non-PVC bags. Hypersensitivity reactions occur in approximately 2% to 3% of patients receiving paclitaxel infusions.9 It is unknown whether the Cremophor or the paclitaxel is responsible for these reactions.18 Regardless, to minimize the risk of hypersensitivity reactions, it is important that patients take an H (histamine)1 antagonist (e.g., diphenhydramine) or an H2 antagonist (e.g., famotidine) 30 minutes prior to infusion, and dexamethasone or another steroid equivalent 12 hours and 6 hours prior to receiving paclitaxel. Paclitaxel’s black box warning states that the drug has been associated with fatal hypersensitivity reactions despite prophylaxis.17 Patients who experience a severe hypersensitivity reaction should not receive another dose of paclitaxel.17

Carboplatin: Carboplatin is an alkylating-like agent that binds to DNA and prevents replication.17 Other well-known agents in the platinum class are cisplatin and oxaliplatin. Carboplatin’s dose-limiting toxicity is bone-marrow suppression. The degree of suppression may be so severe that a patient has an increased susceptibility to infection. Other significant side effects are peripheral neuropathy, ototoxicity, nephrotoxicity, and nausea and vomiting. The incidences of these side effects are lower than for cisplatin, although 65% of patients receiving carboplatin experience nausea and vomiting.17 Pharmacists should be aware that carboplatin is dosed based on a target AUC. Most regimens start with a carboplatin AUC of 5.0 to 7.5.8 The calculation of how to dose carboplatin based on AUC is as follows: carboplatin in mg = AUC x (creatinine clearance [CrCl] in mL/min + 25).17

Hypersensitivity reactions may occur with carboplatin, and they can be quite severe. The literature indicates that incidence increases after patients have received 4 to 6 cycles of carboplatin and that 27% of patients receiving more than 7 cycles will experience a reaction.18 Pharmacists must ensure that epinephrine is readily available to reverse symptoms of hypotension, edema, bronchospasm, and tachycardia. Some practitioners perform skin testing to identify patients who may have a reaction; others utilize carboplatin-desensitization protocols in order to continue the carboplatin.19,20

Antiemetics: Appropriate antiemetic therapy should be prescribed for patients receiving carboplatin and paclitaxel. This regimen should include a serotonin receptor antagonist such as ondansetron; dexamethasone; and an agent such as prochlorperazine for breakthrough nausea and vomiting on an as-needed basis. Aprepitant also may be used for delayed nausea and vomiting. The delayed nausea and vomiting occurring with carboplatin typically are less severe than with cisplatin.21

Stages

Early-Stage Ovarian Cancer: For early-stage disease, the goal of treatment is cure. Early-stage ovarian cancer can be divided into two categories based on risk of recurrence. Patients with stage IA–IB, grade 1 disease are considered to have favorable features and a low risk of recurrence; patients with stage IA–IB, grade 2–3 disease; stage IC with any grade; or stage II disease are considered to have unfavorable features and a high risk of recurrence.8,9 Treatment for favorable early-stage ovarian cancer consists of comprehensive surgical staging and observation. Because the survival of patients with favorable early-stage ovarian cancer is greater than 90%, chemotherapy administered after surgery (adjuvant chemotherapy) is not recommended.8

Adjuvant chemotherapy is essential in treating unfavorable early-stage ovarian cancer. Patients first undergo comprehensive surgical staging and then receive chemotherapy with a taxane and a platinum, usually paclitaxel in combination with carboplatin. With this regimen, typically given in the outpatient setting, paclitaxel 175 mg/m2 is infused over 3 hours, followed by carboplatin AUC 5.0 to 7.5 infused over 30 minutes; this regimen is administered every 3 weeks for 3 to 6 cycles.8 Other chemotherapy options include docetaxel with carboplatin and paclitaxel with cisplatin.8 Stage II patients may benefit from IP/IV chemotherapy, which is discussed in detail in the next section.

Late-Stage Ovarian Cancer: Patients with Stage III–IV disease are considered to have late-stage ovarian cancer, which has a reduced probability of cure. Comprehensive surgical staging and debulking (removal of tumor tissue) is similar to that for early-stage ovarian cancer. The vast majority of patients receive combination chemotherapy with a taxane and a platinum. Current guidelines state that IP chemotherapy may be the preferred route of administration for patients with stage III disease that has been optimally debulked (<1 cm cancerous tissue remaining after surgery).8 Patients who have stage IV ovarian cancer or who are not candidates for IP/IV chemotherapy receive IV chemotherapy alone. The regimen of a taxane with a platinum compound is essential in the treatment of these patients.

IP chemotherapy has been used since the 1950s to deliver chemotherapeutic agents directly to the tumor site. Cisplatin and paclitaxel have been used IP, with cisplatin being the best-studied drug administered via the IP route. Both of these drugs are reasonable choices since they are active agents in ovarian cancer and are associated with limited local toxicity.22 Other advantages of IP therapy include longer half-life when given IP compared with IV, longer exposure of the tumor to chemotherapy, and lower systemic levels of the drugs.22 There has been an increase in the use of IP chemotherapy based on data from three large phase III trials that examined the use of IP chemotherapy versus IV chemotherapy alone in stage III ovarian cancer.23-25 The results were so impressive that the National Cancer Institute announced that all three trials demonstrated an improvement (two were significant; the third was borderline) in survival when IP chemotherapy was administered.26 The greatest improvement in median survival, shown by the Armstrong trial, was 16 months.25 IP chemotherapy was quickly incorporated into the guidelines as an acceptable regimen for patients with stage III disease. The National Comprehensive Cancer Network guidelines have extrapolated findings from these clinical trials to patients with stage II disease, although this is controversial.8

Case Study
Patient is a 48-year-old Caucasian female reporting left-sided abdominal pain worsening over the past 2 weeks. She reports having predictable menstrual cycles, most recently last month.
Past Medical History: Unremarkable.
Family History: Father with colon cancer; maternal aunt with cervical cancer; history of breast cancer on both sides of family.
Social History: 20-pack/year history of smoking. Last Pap smear (7 months ago) was normal.
Physical Examination: Weight: 171 lb; height: 64 in.
General: Quite healthy and ambulatory.
Lymph nodes: No cervical or supraclavicular adenopathy.
Lungs: Clear.
Heart: Normal.
Abdomen: Palpable mass approximately 2 fingerbreadths above umbilicus. No adenopathy in groin.
Labs: CA-125 elevated at 284 (normal range: <35 U/mL).
Tests: Ultrasound shows large pelvic abdominal mass.
Plan: Patient to undergo surgical exploration by gynecologic oncologist, with total abdominal hysterectomy and bilateral salpingo-oophorectomy.
Following Surgery: Patient is found to have stage IIIC, optimally debulked, poorly differentiated adenocarcinoma of ovary. She receives 6 cycles of IV/IP chemotherapy with cisplatin and paclitaxel. Her CA-125 after cycle 5 is 9. CA-125 monitoring is performed every 3 months.
2 Years Later: CA-125 remains low at 4. Patient has done exceedingly well with treatment and continues to have no clinical evidence of disease.
3 Years Later: Patient presents with right lower-quadrant pain as well as some bloating experienced for the past month. CA-125 has risen to 106 U/mL. CT scan confirms recurrence in pelvis. No masses are found in chest or abdomen. Patient will receive carboplatin and paclitaxel for recurrent ovarian cancer.
CA-125: cancer antigen 125; IP: intraperitoneal.

Since many clinicians are not familiar with IP chemotherapy, an in-depth discussion of how IP chemotherapy is administered is warranted. Most patients have an IP port placed into the peritoneal cavity at the time of comprehensive surgical staging. When a patient receives IP chemotherapy, the head of the bed should be placed at a slight angle to lessen gastrointestinal (GI) discomfort. Unlike IV chemotherapy, IP chemotherapy is infused via gravity, so it may take 30 minutes to 3 hours to complete.

There are several IP/IV regimens, with the most recent trial using IV paclitaxel 135 mg/m2 on day 1, IP cisplatin 100 mg/m2 on day 2, and IP paclitaxel 60 mg/m2 on day 8 to complete 1 cycle. This regimen is repeated every 3 weeks for 6 cycles.8 Many institutions recommend warming the 2-L bag of normal saline (diluent) in a water bath to lessen GI discomfort.25 Unfortunately, the IP/IV routes of administration are associated with significant side effects, and fewer than half of patients are able to complete all 6 cycles.8 Side effects include catheter-related infections, leukopenia, nausea and vomiting, fatigue, and pain.22

Monitoring

Patients with ovarian cancer are monitored frequently. CA- 125 levels are monitored to assess response to treatment. Imaging studies such as CT scans are routinely performed to check for evidence of disease. A decrease in CA- 125 levels is desired, and an increase in CA-125 without signs or symptoms often suggests tumor progression. A clinical relapse usually occurs 2 to 6 months after the increase in CA-125.8

Recurrent Disease

More than 50% of women with ovarian cancer will have a recurrence despite undergoing chemotherapy.27 The prognosis for recurrent disease is quite poor, especially if time to recurrence is less than 6 months.8 Treatment depends upon the duration of response to initial chemotherapy. If the duration of response is more than 6 months, the disease is considered to be platinum-sensitive, and it may respond to another round of paclitaxel and carboplatin. Other options include gemcitabine and carboplatin or single-agent paclitaxel or carboplatin. Patients with platinum-sensitive disease have more options than patients whose disease recurs in less than 6 months (platinum-resistant disease). Patients with platinum-resistant disease may consider a clinical trial, supportive care, or a regimen that does not contain a platinum, such as topotecan or docetaxel.8 Currently, no chemotherapy agent has demonstrated outcomes superior to other agents.8

Antiangiogenesis drugs also have been studied for recurrent ovarian cancer. Higher levels of vascular endothelial growth factor (VEGF) have been correlated with poorer outcomes and more aggressive disease.28 Bevacizumab is a monoclonal antibody used to block VEGF. The response rate for bevacizumab used to treat recurrent ovarian cancer is between 16% and 35%.27 Despite bevacizumab’s activity, the drug’s side-effect profile limits its use. A phase II trial evaluating bevacizumab for recurrent ovarian cancer was halted because 11.4% of patients developed GI perforation.29 Recent studies suggest that bevacizumab should be used only in selected patients, such as those without bowel obstructions and those who have received minimal chemotherapy regimens.27,29

Clinical Studies

More than 950 clinical trials have investigated or are currently studying drug therapy for ovarian cancer.30 Most research has focused on stage II–IV ovarian cancer in the hope of improving survival outcomes. Numerous studies have investigated the use of monoclonal antibodies and oral small-molecule inhibitors (e.g., vorinostat, lapatinib). Unfortunately, results of most of the research on these drugs in advanced ovarian cancer have not been favorable. Trastuzumab (human epidermal growth factor receptor- 2 inhibitor) and erlotinib (tyrosine-kinase inhibitor) have not demonstrated any benefit in advanced disease.31

One drug that holds promise for ovarian cancer is trabectedin (Yondelis), an orphan drug used to treat soft-tissue sarcomas; it also has been studied as an alternative to a platinum-based regimen in relapsed ovarian cancer.32 Other areas of research include optimizing the dosing frequency of the chemotherapy drugs currently utilized. Treatment for ovarian cancer is in dire need of a breakthrough from one of these clinical trials.

THE PHARMACIST’S INVOLVEMENT

The pharmacist should play an integral part in the treatment of ovarian cancer. The pharmacist needs to be especially familiar with paclitaxel and carboplatin. Patients undergoing chemotherapy with paclitaxel and carboplatin encounter significant side effects that can be managed by a pharmacist. The pharmacist should know how to manage chemotherapy toxicities, including nausea and vomiting; understand how to prevent and treat hypersensitivity reactions; and be familiar with the administration of IP chemotherapy. It is important to remember that paclitaxel infusions must be prepared in a non-DEHP bag.

CONCLUSION

Ovarian cancer remains one of the deadliest cancers. Unfortunately, no screening method has been discovered that can identify patients with early-stage disease. Practitioners must be aware that abdominal pain, bloating, early satiety, and urinary frequency may be early symptoms of ovarian cancer and should not be overlooked. Treatment for early-stage ovarian cancer consists of surgery, and cure is possible. Chemotherapy with paclitaxel and carboplatin is essential in treating late-stage disease and is often palliative in nature. IP chemotherapy is being used in stage III ovarian cancer as a means of improving disease control.

References

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