OVARIAN CANCER

February 26, 2007 Paula Kwong, RPh Pharm D Candidate

INTRODUCTION

• 6 th most common malignancy in women (excluding skin cancers) • 4 th leading cause of cancer related death in women • Incidence highest in US, Europe, Israel • Lowest incidence developing countries & Japan • 1 in 56 to 1 in 70 women will develop ovarian cancer; lifetime risk of about 1-2% • 2006 estimates: 20,180 cases and 15,310 deaths

INTRODUCTION…

• 5 yr survival for all stages nearly 50% • Survival for patients with localized disease nearly 90%, but only 10-30% with disseminated disease • 70% of patients diagnosed with disseminated disease • Early detection is critical

PRESENTATION- symptoms

• Vague and non-specific; can be confused with GI, urinary tract, stress, and menstrual problems • Early symptoms: nausea, dyspepsia, flatulence, bloating, fullness, early satiety, abdominal pain, urinary urgency & frequency

PRESENTATION-symptoms (2)

• May also complain of: • Dyspareunia • Low back pain • Lack of energy • Menstrual irregularities

PRESENTATION-physical signs

• May have palpable abdominal mass • May have lymphadenopathy • May have signs of ascites • May have abnormal hair growth • Red flag: palpable ovary in postmenopausal woman or before puberty

PRESENTATION- other facts

• Two-thirds of women with ovarian cancer are 55yo or older • More common in caucasians • Can occur in females before puberty • Majority of cases occur sporadically with only 5 to 10% being familial

DIFFERENTIAL (1)

• Ovarian Cysts • Ectopic Pregnancy • Pelvic Inflammatory Disease • Uterine Fibroids • Other gynecologic cancers • Other cancers: GI, pancreatic, colon/rectal

DIFFERENTIAL (2)

• Pelvic kidney • Diverticulitis • Hepatic failure • Colitis • Irritable Bowel Syndrome • Inflammatory Bowel Disease

METASTATIC SPREAD

• Intraperitoneal: pelvic & abdominal viscera, omentum • Bladder & bowel • Transdiaphragmatic spread to pleura, liver • Lymphatics • Hematogenous spread (advanced stage)

RISK FACTORS (1)

• Inherited gene mutations • Age • Family history • Menstrual periods • Nulliparity/Infertility/1 st child after 30yo • Obesity • HRT (hormone replacement therapy)

RISK FACTORS (2)

• Breast Cancer • Ovarian Cysts • Sedentary lifestyle • Smoking & alcohol • Talc • Clomid

PREVENTION

• BCP (birth control pills) • Tubal ligation/hysterectomy/oophorectomy • Pregnancy and breast feeding • Diet/Exercise • Aspirin • Acetaminophen

DIAGNOSIS

• Thorough Physical Exam • Comprehensive Family History • Chest X-ray • Imaging studies: MRI/CT/Ultrasound/Mammogram • Colonoscopy, UGI • Lab tests • SURGERY

LAB TESTS for DIAGNOSIS

• Chem profile including tests for hepatic and renal function • CBC: assess internal bleeding • Pregnancy test if premenopausal • Pap smear • Tumor markers: CA-125, hCG, AFP, CEA

TUMOR MARKERS

• CA-125: Normal= <35 u/ml • Elevated in 85% of ovarian cancers but only 50% of the time in early stage • Elevated in other cancers/benign conditions • Lacks sensitivity and specificity therefore is not diagnostic for ovarian cancer • Most useful for monitoring response to therapy and in detecting recurrence

PROBLEMS WITH CURRENT SCREENING TOOLS

• Rectovaginal Pelvic Exam: lacks sensitivity and specificity • Cancer Antigen-125: CA-125 elevated only 50% of the time in early stage • Transvaginal Sonography: TVS lacks specificity

HISTOLOGY

• Three major histologic (cell) types of ovarian cancer: • Epithelial Cell: 85-95% of cases, cells covering ovaries; 45-75yo • Stromal Cell: connective tissue cells that hold the ovary together and that make hormones • Germ Cell: egg producing cells; most common before age 20

EPITHELIAL CLASSIFICATION

• Developed by WHO/FIGO • Serous: >50% of cases • Mucinous: approx 12% • Endometrioid: approx 10% • Clear cell: approx 3% • Transitional (Brenner), Undifferentiated, Mixed • Low-malignant Potential “Borderline” • Metastatic from other primary • Benign

EPITHELIAL HISTOLOGY

Grading Important • Gx: grade cannot be assesed • G1: well differentiated • G2: moderately differentiated • G3: poorly differentiated • Grade 1 more closely resembles normal tissue and G3 the least

FIGO STAGING OF EPITHELIAL OVARIAN CANCER

• Stage I – tumor confined to one or both ovaries • Stage II – tumor involves one or both ovaries with pelvic extension (metastasis with in pelvis) • Stage III – tumor involves one or both ovaries with metastasis outside pelvis +/- lymph node involvement • Stage IV – distant metastasis beyond the peritoneal cavity

TREATMENT OF EPITHELIAL OVARIAN CANCER

• Guidelines developed by the American Cancer Society and the National Comprehensive Cancer Network • NCCN guidelines available at www.nccn.org

INITIAL TREATMENT

• 1 st step-Surgical debulking at staging laparotomy • 2 nd -Adjuvant chemotherapy • 3 rd -Radiation • Participation in clinical trials encouraged

PROGNOSIS

• Related to stage, subtype & grade, volume of residual disease • Well differentiated IA/IB have 5 yr survival rates of 90% vs 5-10% Stage IV • Survival strongly correlated to size of residual tumors after debulking surgery • Residual tumors <0.5cm: median survival of 40 months; 0.5-2=18 months; >2cm= 6 12 months

NIH SCREENING GUIDELINES

• No reliable, sensitive, specific screening tool exists for women of average risk • ALL WOMEN: assess family history and yearly rectovaginal pelvic exam with Pap smear • No family Hx or 1 relative: participation in ovarian cancer screening trials • Pos family Hx in 2+ relatives: counseling by gynecologic oncologist (specialist)

SCREENING GUIDELINES cont.

• Hereditary Cancer Syndromes: yearly CA 125 + TVS until age 35 or childbearing complete. Prophylactic bilateral oophorectomy should then be considered to reduce overall risk.

• Screening trials

CANCER Jan 15, 2007 Goff, Barbara et al

• Case-control: 149 cancer/458 controls • Symptom index developed • Pelvic/abdominal pain, urinary urgency/frequency, abdominal bloating, early satiety • Frequency/Duration: >12x/mo, <12mo • Correlated to presence of ovarian cancer • Symptoms similar in both early/late stage

CANCER Jan 15, 2007 continued

• Screening test sensitivity = 56.7% early stage & 79.5% for late stage • Specificity was 90% for women > 50 years old and 86.7% for women < 50 years old • National Institute of Health website (medlineplus) says doctors and patients can use the screening test now but more research needed to see if results hold up in larger study

ROLE OF PHARMACIST

• Inpatient/IV infusion pharmacist: dose as per protocol, medication related side effects, nutrition, monitoring for the “fifth” vital sign (JCAHO requirement) • Retail: symptom recognition & referral, medication related side effects, “fifth” vital sign

REFERENCES (1)

• National Comprehensive Cancer Network Practice guidelines in Oncology-Ovarian Cancer. V.1. 2007 www.nccn.org/professionals/physician_gls/ PDF/ovarian.pdf

• DiPiro, JT et al. PHARMACOTHERAPY, A Pathologic Approach. 6 th edition, 2005. Ovarian Cancer. Section 17, pp 2467-84.

REFERENCES (2)

• American Family Physician Sep 15, 2003. Serum Tumor Markers. www.aafp.org/afp/20030915/1075.html

• American Family Physician December 15, 2004. US Preventative Services Task Force-Screening Recommendations for Ovarian Cancer. www.aafp.org/afp/20050215/us.html

REFERENCES (3)

• Naational Cancer Institute Announces Preferred Method of Treatment for Advanced Ovarian Cancer. Jan 4, 2006. www.cancer.govnewscenter/pressreleases /IPchemotherapyrelease