Transcript A lesson in Gynaecological cancer

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
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presentation and diagnosis
staging
prognosis
treatment
What I am not going to talk about…
Ovarian Cancer
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aetiology
pathology
risk factors and genetic susceptibility
screening
Ovarian Cancer- Presentation
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4th commonest female malignancy
4% cancer cases
often presents late
non-specific presentation
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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
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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
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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
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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!