learning objectives by the end of this lecture you have basic knowledge about the benign ovarian...

LEARNING OBJECTIVES

By the end of this lecture you have• Basic knowledge about the benign ovarian tumours• Basic knowledge about the histological types of ovarian cancer• Knowing the clinical presentation and clinical assessment•Outline the treatment of the Ovarian cancer•Have a plan for the follow up

Benign Ovarian Tumours

Benign Ovarian Tumours (cont.)

•Cystic •Solid

Dysfunctional Ovarian Cysts

• Follicle cysts of the ovary are the most common cystic structures found in healthy ovaries

• Result from either failure of a dominant mature follicle to rupture or failure of an immature follicle to undergo the normal process of atresia.

• Solitary follicle cysts are common and occur during all stages of life, from the fetal stage to the postmenopausal period.

Treatment

Generally, no treatment is required, and many of these cysts resolve spontaneously within 6-12 weeks.

Benign Epithelial Neoplastic Ovarian Cysts

• Epithelial cystic tumors account for about 60% of all true ovarian neoplasms.

• One third of all ovarian tumors are serous. • Two thirds of these serous tumors are benign.

•Serous tumors are characterized by proliferation of epithelium resembling that lining the fallopian tubes. • They are virtually all cystic.

• Most commonly seen in women in their 40s and 50s, and are bilateral in 15-20% of cases.

•Mucinous epithelial tumors account for 10-15% of all epithelial ovarian neoplasms.

• 75% are benign and are found in women aged 30-50 years.• They are usually smooth-walled; compared with the serous variety, they rarely are associated with true papillae. • Generally multilocular, and the mucus-containing loculi appear blue through the tense capsules.

• These tumors can grow quite large, measuring up to 30 cm. • Most common in the third to fifth decades of life and are only rarely bilateral. • The larger varieties are associated with an increased risk of rupture, with resultant pseudomyxoma peritonei.

Treatment• For women of childbearing age, simple unilateral oophorectomy via laparoscopy or laparotomy is adequate, provided that the contralateral ovary appears grossly normal.• In women desiring future fertility who have stage IA low-risk ovarian cancer, conservative surgical therapy is appropriate, provided that close follow-up can be maintained.• At the completion of childbearing, usually the remaining ovary and uterus are removed.

• Total abdominal hysterectomy and bilateral salpingo-oophorectomy (with or without staging) are reasonable options for women of perimenopausal age.

Benign Solid Ovarian Tumors• Solid epithelial ovarian tumors are almost invariably malignant.

• Approximately 80% of epithelial tumors are of the serous type, 10% are mucinous, and 10% are endometrioid.

• Rarer varieties including clear cell tumors, Brenner tumors, and undifferentiated ovarian carcinomas.

• Brenner tumors are usually found incidentally at pathologic evaluation, often in conjunction with a mucinous cystadenoma or dermoid cyst.

• They are relatively rare tumors and are most common in the fifth to sixth decades of life.

• Brenner tumors may be benign, intermediate, or malignant transitional cell tumors.

• These tumors are usually small, firm, and solid, and when confined to the ovary, they carry a good-to-excellent prognosis, depending on the malignancy status.

• Common benign solid tumors include fibromas and thecomas.

• Fibromas are the most common benign ovarian neoplasms. • These tumors occur most commonly in women of postmenopausal age. They are unilateral and are often at least 3 cm in size.• Fibromas are connective-tissue tumors that arise from the ovarian cortical stroma. • If the stroma is estrogenic or luteinized, the tumors are actually thecomas.

• Solid mature teratomas are tumors consisting of differentiated tissue from all 3 germ layers.

• Benign teratomas (mature teratomas or dermoid cysts) are likely to contain more of recognizable organic structures, such as thyroid, bronchial, and central nervous system tissue.

• In dermoid cysts, ectodermal structures such as hair, teeth, and skin predominate.

Treatment• In most instances, simple excision of the solid tumors is adequate therapy, particularly for women of reproductive age.

•Laparoscopic treatment of benign cystic teratomas of the ovaries is recommended (ie, laparoscopic ovarian cystectomy).

• In this procedure, in premenopausal women, the contralateral ovary is preserved, and every effort is made to excise only the dermoid cyst itself, thereby leaving both ovaries in situ.

Diagnostic imaging

• Ultrasonography is the standard for identifying ovarian pathology.

• Transvaginal ultrasonography is limited with regard to its role in assessing masses in neonates, children, and virginal adolescents.

• Ultrasonography can be used to evaluate material or fluid contained in a mass, as well as to assess the surface of the ovarian capsule.

• Color-flow Doppler ultrasonography is useful for distinguishing between benign and potentially malignant lesions.

• In most cases, computed tomography (CT) and magnetic resonance imaging (MRI) are unnecessary in the evaluation of an adnexal mass.

• Ultrasonographic findings suggestive of malignancy include :

1. Ovarian mass with solid or complex components2. Septations3. Evidence of surface nodularity or papillae4. Increased vascular flow5. Heterogeneous echotexture

• The presence of pelvic or abdominal ascites or pelvic or abdominal lymphadenopathy on CT or MRI further raises the index of suspicion for ovarian malignancy.

Laboratory studies• The cancer antigen 125 (CA-125) test

• Alpha-fetoprotein (AFP) is another tumor marker that is elevated in the setting of endodermal sinus tumors, mixed germ cell tumors, immature teratomas, and embryonal carcinomas.

•The lactate dehydrogenase (LDH) level may be elevated in women with dysgerminomas.

• Human chorionic gonadotropin (hCG) level may be elevated in women with choriocarcinomas, germ cell tumors, or embryonal cell tumors.

•Testosterone levels may be elevated in patients with fibromas and Sertoli-Leydig tumors, and estradiol levels may be elevated in patients with thecomas or dysgerminomas.

Ovarian Lesions Before Birth and During Childhood

Maternal ovarian cysts during pregnancy• Fairly common

• largely as a result of excessive stimulation of human chorionic gonadotropin (hCG) by the corpus luteum.

• The corpus luteum itself may then become quite large and undergo ovarian torsion.

• Because pregnancy is a time of frequent USS evaluation, the other common ovarian cysts seen in the childbearing age group (eg, dermoid cysts, endometriomas, and, occasionally, malignant epithelial tumors) tend to be diagnosed more frequently during pregnancy.

Fetal cysts Both the maternal and fetal ovaries are exposed to excessive stimulation by human chorionic gonadotropin.

Other maternal hormone levels are also high.

The fetal pituitary gland is also producing follicle-stimulating hormone (FSH), which increases the size and number of fetal ovarian follicles. These factors may contribute to the formation of fetal ovarian cysts.

• Often diagnosed in the third trimester during routine ultrasound surveillance.

• These lesions are typically cystic (99%) and can be either simple or complex. The contralateral ovary also may be cystic.

• Of all fetal cysts, 97% are functional, and the average size is approximately 3.4 cm.

•Half of these cysts spontaneously resolve, and of the remainder, 25-40% undergo torsion.

• The differential diagnosis of an adnexal mass detected in utero includes neoplastic lesions (eg, cystic teratomas, cystadenomas, granuloblastomas); mesenteric cysts; and gastrointestinal, genitourinary, or enteric duplication.

• In the antenatal period, a conservative approach is recommended because many spontaneously resolve.

• Although antenatal aspiration is an option, it has not shown any significant benefit and is not the standard of care.

Ovarian lesions in childhood• Childhood is a time of busy activity for the ovaries.• Histologically, the ovarian stroma is growing, causing the ovaries to enlarge.• When cysts manifest, they are usually small and simple. • The incidence of simple cysts increases with age, and most are caused by a failure of the follicle to undergo involution. • When smaller than 5 cm, these lesions may be followed conservatively.

• Intervention should be considered for: cysts larger than 5 cm, lesions demonstrating solid components, those accompanied by pain, those associated with systemic endocrinologic signs, and those with complex components or internal septations.• When ovarian neoplasms are encountered in girls of this age group, they fall into the germ cell, epithelial cell, and stromal/sex chord familial classification. • The vast majority of ovarian lesions of childhood are of the germ cell variety, but only about 8% of ovarian tumors of childhood are malignant.

Ovarian lesions in adolescence

• With the activation of the hypothalamic-pituitary-ovarian axis that accompanies menarche, an increase occurs in circulating gonadotropin, estrogen, and progesterone levels.

• The axis of an adolescent may remain immature for some time after menarche; this results in frequent anovulatory cycles and ovulatory defects.

• Of the numerous benign ovarian lesions seen in girls of this age group, the functional cyst, the corpus luteum cyst, and the hemorrhagic cyst are the most common.

Ovarian Lesions in Reproductive YearsFibromaThe most common benign solid tumor of the ovary is the fibroma . Fibromas are derived from connective tissue and arise from the solid ovarian cortical stroma. Histologically, spindle cells are seen. Ultrasonographically, these tumors appear hypoechoic with attenuation of the ultrasound beam.

• These tumors may undergo calcification and degeneration. • More than 90% are unilateral, and approximately 10-15% are found in association with ascites. • Fewer than 1% undergo malignant transformation to fibrosarcomas. • About 1% of cases are associated with Meigs syndrome, characterized by ovarian fibroma, ascites, and pleural effusion.

Tubo-ovarian abscess• Tubo-ovarian abscesses (TOAs) are an infectious component of the benign lesions seen in females of reproductive age (see Tubo-ovarian Abscesses). TOAs are present in 14-38% of patients hospitalized with pelvic inflammatory disease (PID).

• Patients usually report abdominal and pelvic pain; may have nausea, vomiting, and diarrhea; and are often febrile.• Physical examination reveals bilateral tender adnexal masses and diffuse peritoneal signs

On imaging studies, TOAs may appear as complex, large, and often bilateral masses, with heterogeneous components on both ultrasonography and CT.Often, the ovarian outline lacks definition, and the periovarian tissue appears thickened. Pyosalpinges may reveal increased echoes within the purulent tubular fluid, and fluid may also be present in the cul-de-sac.

• Treatment includes intravenous (IV) broad-spectrum and anaerobic antibiotic coverage until symptoms resolve.

• Bilateral salpingo-oophorectomy, with or without hysterectomy, is a last resort and should only be undertaken acutely in the presence of severe sepsis.

Polycystic ovary syndrome

Currently, 2 of the following 3 criteria are required to establish the diagnosis of PCOS:

• Polycystic ovaries (multiple small cysts, often around the periphery of the ovary—the classic “string of pearls” appearance)• Signs of androgen excess (eg, acne, hirsutism, temporal balding, male pattern hair loss, or clitoromegaly)• Menstrual irregularities (oligomenorrhea or polymenorrhea)

Ultrasonographic findings suggestive of PCOS commonly include the following:

• Ovarian enlargement• Increased follicle count• Stromal echogenicity

Endometriomas• An estimated 1-10% of reproductive-age women may have endometriosis to some degree.

• The differential diagnosis of endometriomas also includes hemorrhagic cysts, TOAs, and ovarian malignancies.

OVARIAN MALIGNANCY

Estimated new cases and deaths from ovarian cancer in the United States in 2014:New cases: 21,980Deaths: 14,270

The incidence rate for ovarian cancer between 2006 and 2010 was 12.5 cases per 100,000 women.

BRCA1 and BRCA2: Cancer Risk

Causes and Risk Factors

Oral Contraceptives and Cancer RiskOral Contraceptives and Cancer Risk

Factors With Adequate Evidence of Increased Risk of Ovarian Cancer Hormone replacement therapy Perineal talc exposure Obesity, weight gain and height

Factors With Adequate Evidence for a Decreased Risk of Ovarian Cancer Oral contraceptives Tubal ligation Breast-feeding Risk-reducing bilateral salpingo-oophorectomy

Areas of Uncertainty Ovarian hyperstimulation for infertility treatment

Cellular Classification of Ovarian Epithelial Cancer

Serous cystomas: Serous benign cystadenomas. Serous cystadenomas with proliferating activity of the epithelial cells and nuclear abnormalities but with no infiltrative destructive growth (low potential or borderline malignancy). Serous cystadenocarcinomas.

Mucinous cystomas: Mucinous benign cystadenomas. Mucinous cystadenomas with proliferating activity of the epithelial cells and nuclear abnormalities but with no infiltrative destructive growth (low potential or borderline malignancy). Mucinous cystadenocarcinomas.

Endometrioid tumors Endometrioid benign cysts. Endometrioid tumors with proliferating activity of the epithelial cells and nuclear abnormalities but with no infiltrative destructive growth (low malignant potential or borderline malignancy).

Endometrioid adenocarcinomas. Clear cell (mesonephroid) tumors:

Benign clear cell tumors. Clear cell tumors with proliferating activity of the epithelial cells and nuclear abnormalities but with no infiltrative destructive growth (low malignant potential or borderline malignancy).

Clear cell cystadenocarcinomas.

Unclassified tumors that cannot be allotted to one of the above groups. No histology. Other malignant tumors (malignant tumors other than those of the common epithelial types are not to be included with the categories listed above).

Cellular Classification of Ovarian Germ Cell Tumors

Dysgerminoma.Other germ cell tumors:

Endodermal sinus tumor (rare subtypes are hepatoid and intestinal).Embryonal carcinoma.Polyembryoma.Choriocarcinoma.

Teratoma: Immature.Mature:

Solid.Cystic:

Dermoid cyst (mature cystic teratoma).Dermoid cyst with malignant transformation.

Monodermal and highly specialized: Struma ovarii.Carcinoid.Struma ovarii and carcinoid.Others (e.g., malignant neuroectodermal and ependymoma).

Mixed forms.

Description of stagesStage I:Growth limited to the ovariesStage IA:Growth limited to 1 ovary, no tumor on the external surface, capsule intact, no ascites present containing malignant cellsStage IB:Growth limited to both ovaries, no tumor on the external surfaces, capsules intact, no ascites present containing malignant cellsStage IC:Tumor either stage IA or IB, but with tumor on surface of 1 or both ovaries with capsule ruptured,* with ascites present containing malignant cells, or with positive peritoneal washingsStage II:Growth involving 1 or both ovaries with pelvic extensionStage IIA:Extension and/or metastases to the uterus and/or tubes

Stage IIB:Extension to other pelvic tissuesStage IIC:Tumor either stage IIA or IIB, but with tumor on surface of 1 or both ovaries, with capsule(s) ruptured,* with ascites present containing malignant ovaries, or with positive peritoneal washingsStage III:Tumor involving 1 or both ovaries with histologically confirmed peritoneal implants outside pelvis and/or positive retroperitoneal or inguinal nodes; superficial liver metastasis; tumor limited to true pelvis, but with histologically proven malignant extension outside of the pelvis

Stage IIIA:Tumor grossly limited to the true pelvis, with negative nodes, but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces outside of the pelvisStage IIIB:Tumor of 1 or both ovaries with histologically confirmed implants, peritoneal metastasis of abdominal peritoneal surfaces ≤ 2 cm in diameter; nodes are negativeStage IIIC:Peritoneal metastasis beyond the pelvis > 2 cm in diameter and/or positive retroperitoneal or inguinal nodesStage IV:Growth involving 1 or both ovaries with distant metastases; if pleural effusion is present, positive cytology must be apparent to allot a case to stage IV; parenchymal liver metastasis qualifies as stage IV disease

Clinical presentation

•Fague•Bloating•Abdominal distention•Constipation•Abdominal pain

Investigations

•Biochemistry•Tumour markers•USS•CT Scan•MRI

OVARIAN MALIGNANCY TREATMENT

Surgical:• Debulking • StagingIncludes: TAH+ BSO+OMENTECTOMY+LNS DISSECTION + PERIOTONEAL CYTOLOGY

ADJUVANT CHEMOTHERAPY

Cysplatinum- based chemotherapy

Chemotherapy recommendations based on stageStage I:Consider chemotherapy for stages 1A and 1B grades 2 and 3, and stage 1C. Chemotherapy is usually given after surgery.Paclitaxel 175 mg/m2 IV over 3h plus carboplatin AUC 6 IV over 30min on day 1; every 21d for 3-6 cycles[ orDocetaxel 75 mg/m2 IV over 1h plus carboplatin AUC 5 IV over 1h on day 1; every 21d for 3-6 cycles (by inference from Bell et al orCarboplatin AUC 5 IV over 1h on day 1; every 21-28d for 6 cycles orCarboplatin 350 mg/m2 IV over 1h on day 1; every 21-28d for ≥ 4 cyclesStages IIA and IIB:All patients with stage II or higher cancer should be considered for front-line chemotherapy and should strongly

Stages IIA and IIB:All patients with stage II or higher cancer should be considered for front-line chemotherapy and should strongly consider participation in clinical trials if the option is available. Paclitaxel 175 mg/m2 IV over 3h plus carboplatin AUC 7.5 IV over 30min on day 1; every 21d for 3-6 cycles orDocetaxel 75 mg/m2 1h IV infusion plus carboplatin AUC 5 IV over 1h on day 1; every 21d for 3-6 cycles (from Vasey et al[4] and by inference from Bell et al[) orCarboplatin AUC 5 IV over 1h on day 1; every 21-28d for 6 cyclesorCarboplatin 350 mg/m2 IV over 1h on day 1; every 21-28d for ≥ 4 cycles

Stage IIC:All patients with stage IIC cancer should be considered for treatment as for stage III cancer (see below).Stage III:Patients with optimally debulked (≤ 1 cm) stage III ovarian cancer after front-line surgery should be offered intraperitoneal (IP) chemotherapy. The Gynecological Oncology Group (GOG) trial compared IV cisplatin and paclitaxel with IP cisplatin and paclitaxel; results showed that IP therapy improved survival and yielded a 25% reduction in the risk of death. The trial also showed that IP chemotherapy resulted in increased toxicity when compared to IV chemotherapy

At this time, there is no standardized regimen for IP therapy; however, the following dosing regimens may be used:Paclitaxel 135 mg/m2 IV over 24h on day 1 plus cisplatin 100 mg/m2 IP on day 2 (may reduce dose to 75 mg/m2) plus paclitaxel 60 mg/m2 IP on day 8 for ≥ 6 cycles, provided that the disease is responsive[8]

Clinicians may reduce the cisplatin dose to 75 mg/m2 IP on day 2, and some give paclitaxel 135 mg/m2 IV over 3h followed by cisplatin 75 mg/m2 IP, both on day 1 and on an outpatient basis[9]

Normal range of carboplatin AUC for treatment of ovarian carcinoma ranges from 5 to 7.5; patients who have received extensive prior chemotherapy or radiation should start with an AUC < 5 If patient cannot tolerate IP delivery, revert to 1 of the 2 drug regimens listed below:Paclitaxel 175 mg/m2 IV over 3h plus carboplatin AUC 7.5 IV over 1h on day 1; every 21d for 6 cycles[10] orDocetaxel 75 mg/m2 IV over 1h plus carboplatin AUC 5 IV over 1h on day 1; every 21d for 6 cycles

Stage IVA:Treatment recommendations are similar to those for stage III.Stage IVB:Patients should be considered for front-line chemotherapy and should strongly consider participation in clinical trials if the option is available. Paclitaxel 175 mg/m2 IV over 3h plus carboplatin AUC 7.5 IV over 1h on day 1; every 21d for 6 cycles[10] orDocetaxel 75 mg/m2 IV over 1h plus carboplatin AUC 5 IV over 1h on day 1; every 21d for 6 cycles[6]

Chemotherapy recommendations for patients with implants > 1 cm after surgery

Paclitaxel 175 mg/m2 IV over 3h plus carboplatin AUC 7.5 IV over 1h on day 1; every 21d for 6 cycles, provided that the disease is responsive[10] orDocetaxel 75 mg/m2 IV over 1h plus carboplatin AUC 5 IV over 1h on day 1; every 21d for 6 cycles, provided that the disease is responsive[6]

*The addition of bevacizumab to front-line therapy is still controversial

Chemotherapy recommendations for consolidation

Consolidation is treatment given after completion of front-line therapy with a complete clinical or pathologic response.Patients treated for stage III or IV disease have a high rate of recurrence. Patients with stage III or IV disease in this situation should be considered for clinical trials. The use of bevacizumab for consolidation is still controversial.[11]

Chemotherapy recommendations for recurrent disease

Treatment is usually with chemotherapy; the treatment choice is dependent on the time interval from previous complete response to platinum containing chemotherapy. Platinum-sensitive recurrence:If recurrence occurs > 6mo from initial or subsequent complete clinical response to platinum-containing chemotherapy, the patient should be treated with one of the IV platinum-containing combination regimens below. The choice depends on factors such as preexisting comorbidity, prior toxicities and physician and patient preference. See the following: Carboplatin AUC 5 IV push plus liposomal doxorubicin 30 mg/m2 IV over 30 min; every 28d for 6 cycles[12] orPaclitaxel 175 mg/m2 IV over 3h plus carboplatin AUC 5 (Calvert) IV over 1h; every 21d for 6 cycles[13] orPaclitaxel 80mg/m2 IV over 1h weekly days 1, 8, and 15 plus carboplatin AUC 6 IV over 1h on day 1; every 21 days for 6 cycles[14] orDocetaxel 75 mg/m2 IV over 1h plus carboplatin AUC 5 IV over 1h; every 21d for 6 cycles[6] orGemcitabine 1000mg/m2 IV over 30 min days 1 plus 8 plus carboplatin AUC 4 IV over 1h on day 1; every 21 days for 6 cycles[15, 16]

Consideration may be given to bevacizumab either alone[17] or with carboplatin/gemcitabine,[18] but the use of this agent is still controversial. See the following: Bevacizumab 15 mg/m2 IV (initially over 90min, then over 60min, and finally over 30min for subsequent infusions); every 21d until disease progression, irrespective of prior platinum response[17]

Gemcitabine 1000 mg/m2 IV over 30 min on days 1 and 8 plus carboplatin AUC 4 IV push on day 1; every 21d for 6-10 cycles plus bevacizumab 15 mg/kg IV on day 1 prior to gemcitabine and carboplatin and continued until progressive disease or unacceptable toxicity[18]

A minority of patients may be suitable candidates for secondary surgery, including those with limited disease and a long interval to recurrence from original treatment. All patients should be considered for entry into clinical trials. Platinum-resistant recurrence:If recurrence occurs ≤6mo from initial or subsequent complete clinical response to platinum-containing chemotherapy, the patient should be treated with one of the following regimens below. There is no standard for the number of cycles of treatment given in this situation. Often treatment is changed because of progressive disease or toxicity. Although liposomal doxorubicin is a good first choice, there are many agents available with similar efficacy and the final choice depends on individual circumstance and patient and physician preference. Some of the choices include the following:

Liposomal doxorubicin 40-50 mg/m2 IV over 30min; every 21d[19, 20, 21] orGemcitabine 1000 mg/m² IV over 30min on days 1 and 8; every 21d[20, 21, 22] orTopotecan 1.25-1.5 mg/m2 IV over 30min on days 1-5; every 21d[19, 23] orPaclitaxel 80mg/m2 IV over 1h weekly[24, 25, 26] orDocetaxel 75-100mg/m2 IV over 1h q21 days[27, 28] orEtoposide 50/m2/day PO for 21 days q28 days[29] orNanoparticle albumin-bound paclitaxel 100 mg/m2 IV over 30 min given weekly days 1, 8, and 15 q28 days[30]

Consideration may be given to bevacizumab as a single agent or in combination, as follows:Bevacizumab 15 mg/m2 IV (initially over 90min, then over 60min, and finally over 30min for subsequent infusions); every 21d until progression[17,

31] orBevacizumab 10mg/kg IV on days 1 and 15 plus topotecan 4 mg/m2 IV on days 1, 8, and 15 q28 days[32]

Hormonal therapy may be considered for patients who have asymptomatic recurrence or who require a break from regular chemotherapy if they are not tolerating treatment well, as follows: Tamoxifen[33, 34, 35] 20mg PO twice a day daily orLetrozole[36] 2.5mg PO daily All patients should be considered for entry into clinical trials.Special considerations

Elderly patients may not tolerate chemotherapy as well as younger patients.

Comorbid conditions affect tolerance to chemotherapy and necessitate close monitoring and dose reductions; such conditions may include liver or renal dysfunction. See the following: Carboplatin can be given at a reduced starting dose of AUC 4-5 plus paclitaxel 135mg/m2; every 21d[37] orCarboplatin may be given weekly at AUC 2 IV over 1h plus paclitaxel 80mg/m2 IV over 2h on days 1, 8, and 15; every 28d[38] orSingle-agent carboplatin may be given at AUC ≥4- 5 IV push; every 21-28d or AUC 2 weeklyPatients considered not fit for initial front-line surgery (including those with a recent pulmonary embolus) can be considered for neoadjuvant chemotherapy for 3 cycles[39] with one of the following combined platinum-taxane chemotherapy regimens: Paclitaxel 175mg/m2 IV over 3h plus carboplatin in AUC 7.5 IV over 1h on day 1; every 21d[9] orDocetaxel 60-75mg/m2 IV over 1h plus carboplatin AUC 5 IV over 1h on day 1; every 21d[6]

Prognosis in ovarian cancer is influenced by :

• Younger age.• Good performance status.• Cell type other than mucinous and clear cell.• Lower stage.• Well-differentiated tumor.• Smaller disease volume prior to any surgical debulking.• Absence of ascites.• Smaller residual tumor following primary surgery.

Treatment Options for Patients with Recurrent or Persistent Disease • Secondary cytoreduction has been advocated, but it remains controversial. • For patients with platinum-sensitive disease (i.e., ≥6–12 mo between completion of a platinum-based regimen and the development of recurrent disease), retreatment with a platinum or platinum-containing combination, such as carboplatin, should be considered .

• For patients with platinum-refractory or platinum-resistant disease (i.e., disease that has progressed while on a platinum-based regimen or has recurred within 6 months of completion of a platinum-based regimen), clinical trials should be considered.