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Radiotherapy and Chemotherapy in Gynaecology Cancers The Treatment of Ovarian Cancer Dr Michelle Ferguson What do you know about ovarian cancer? “its rare in men” What I am going to talk about… Ovarian Cancer • • • • presentation and diagnosis staging prognosis treatment What I am not going to talk about… Ovarian Cancer • • • • aetiology pathology risk factors and genetic susceptibility screening Ovarian Cancer- Presentation • • • • 4th commonest female malignancy 4% cancer cases often presents late non-specific presentation – – – – ascites/ bloating pelvic mass/ bladder dysfunction pleural effusion/shortness of breath incidental finding Ovarian Cancer-Diagnosis • Blood test- CA125 • ultrasound- transvaginal/abdominal • cytology- pleural fluid/ ascites • pathology Ovarian Cancer-Pathology • 90% epithelial cell tumours of ovary – – – – – serous mucinous endometrioid clear cell undifferentiated • 10% germ cell, granulosa cell Ovarian Cancer-Staging FIGO stage:I- confined to 1 or both ovaries II-spread to other pelvic organs eg uterus, fallopian tubes III- spread beyond the pelvis within the abdomen IV- spread into other organs eg liver, lungs Ovarian Cancer-Prognosis Stage 5 year survival I 80-90% II 65% III 15-35 IV up to 15% Ovarian Cancer- Treatment • Surgery (TAH, BSO, omentectomy, optimal debulking) • surgery and chemotherapy • chemotherapy and surgery • timing and sequence Ovarian Cancer-Chemotherapy • response rates of 60-70%- carboplatin/ paclitaxel • relapse rates high • palliative chemotherapy- carboplatin, paclitaxel, etoposide, caelyx, topotecan, gemcitabine, chlorambucil etc etc • most with advanced disease recur • relapsing, chronic illness • some receive many classes of chemotherapeutic agents before their disease becomes truly drug resistant Hope for “cure” “Cure” unrealistic Surgery/Chemotherapy “Chronic disease” / Multiple lines of therapy Platinum/paclitaxel presentation Caelyx Plat/pac relapse Topotecan Etop Tam death Ovarian Cancer-Advanced Disease • 70% present with advanced disease, rarely cured • ? addition of a 3rd drug • ? intraperitoneal chemotherapy • ? maintenance therapy • ? targeted therapy • ? neo-adjuvant chemotherapy Intraperitoneal Chemotherapy • rational- bulk of disease is in peritoneal cavity • increase [cytotoxic] locoregionally • several trials (GOG172) show superiority over the same drugs given intravenously Intraperitoneal Chemotherapy • • • • GOG172 improved PFS ( 24 versus18 months) improved OS ( 66 versus 50 months) only 42% received planned ip dose • at least 3 trials with same conclusions plus Cochrane meta-analysis in favour of ip chemo • debate continues and further trials planned Ovarian Cancer-New Biological Treatments • Bevacuzimab- VEGF (vascular endothelial derived growth factor) • PARP inhibitors- PARP-1 ( DNA single strand break repair enzyme) • Decitabine- methylase inhibitors Targeted Therapy • “biological” therapies • Specific molecular targets • Front runner- antiangiogenic therapy, antiVEGF antibody • 15% (bevacizumab) in platinum resistant ovarian cancer • ICON-7 Targeted Therapy • agents targeting EGF and tyrosine kinases • modest single agent activity but toxicity problematic when combined with cytotoxics Ovarian Cancer- Hormone Manipulation • Tamoxifen- 10% ovarian cancers respond to tamoxifen with about 30% achieving disease stabilisation Cochrane review • Letrozole-stopped tumour growth in 25% ER +ve cancers, maintained for >6 months. Smyth J et al. Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen-receptor positive patients. Clinical Cancer Research 13;12:3617-3622. Treatment Goals for Ovarian Cancer • • • • • • cure prolong survival achieve a durable objective response improve cancer related symptoms optimise quality of life delay time to (symptomatic) disease progression UPDATE 2-Roche's Avastin helps in ovarian cancer “ZURICH, Feb 25 (Reuters) - Roche's (ROG.VX) Avastin helps women with advanced ovarian cancer live longer without their disease getting worse, a late-stage study showed, boosting its prospects after a recent setback in stomach cancer. Roche, the world's largest maker of cancer drugs, said on Thursday it was the first positive Phase III study of an anti-angiogenic therapy, which uses drugs to stop tumours from making new blood vessels, in advanced ovarian cancer.” 3 March 2010 Older women with suspected ovarian cancer 'face referral delays' “Women aged 45 to 69 were typically referred within ten weeks of visiting their GP, whereas those aged between 75 and 79 years usually waited for 20 weeks before seeing a specialist.” Women Missing Ovarian Cancer Signs Channel 4 news 26/2/2010 “Almost one in three women (29%) mistakenly believe a smear test will pick up signs of ovarian cancer a poll has found. Only 4% are confident they could spot symptoms of the disease themselves and many believe it is less common than cervical cancer. Some 6,800 women are diagnosed with ovarian cancer every year and 4,500 die from it, four times as many as die from cervical cancer.” “Battling a silent killer 22 February 2009 By Ruth Walker” Theres one in every holiday snap!