Ovarian Cancer: Treatment Options after Diagnosis

Ovarian Cancer: Treatment Options after Diagnosis Mildred R. Chernofsky, MD Sibley Center for Gynecologic Oncology and Advanced Pelvic Surgery Ovarian Health: Knowledge is Power Community Lecture Series 15 September 2009

Ovarian Cancer
Second Most Common Gynecologic Cancer
3% of all cancers diagnosed in women
21,550 new ovarian cancers (2009)
14,600 deaths (2009)
Leading Cause of Gynecologic Cancer Death
More women die of ovarian cancer than cervical and endometrial cancer combined
At presentation:
About 3/4 will have Advanced Disease
Only ¼ will have Early Disease
American Cancer Society, Cancer Facts and Figures 2009

Ovarian Cancer is a:
Surgically Staged Disease:
Extent of disease is determined at time of surgery by removal of specific organs and biopsies
Why is stage important?
Prognosis
Need for additional treatment besides surgery: (chemotherapy)

Ovarian Cancer Staging: Surgery
Peritoneal washings (Cytology)
Intact removal of the tumor (removal of both tubes and ovaries) + Hysterectomy
Inspection of all peritoneal surfaces + multiple biopsies
Lymph node assessment: (pelvic and aortic)
Removal of the omentum

Tumor Staging

Ovarian Cancer is a
Surgically Treated Disease:
In presence of extensive disease (surgical debulking/cytoreduction)
Removing as much tumor as possible is critical:
Best: no residual cancer (optimal)
Next best: remaining tumor nodules be very small (less than 1 cm) (optimal)
This means we remove, if necessary, in addition to the uterus, tubes, ovaries and omentum,: sometimes the spleen, some bowel, some surface lining (peritoneal lining)
When pts have large residual disease: suboptimal
This approach confers a survival advantage
Optimal versus suboptimal (11 months median survival improvement)*
Optimal median survival 33.9 months
Suboptimal medical survival 22.7 months
*Bristow RE, JCO 2002;20:1248-1259

Ovarian Cancer Patient Populations
Limited disease (resected) and low risk for recurrence
Risk of recurrence: 10 %
Limited disease (resected) and high risk for recurrence
High risk: grade, high risk cell type (clear cell), surface ovarian disease, disease outside the ovary, ascites or positive washings)
Recurrence risk: 20-35%
Small volume residual advanced disease ( optimal cytoreduction )
High risk for recurrence: 65-75%
Large volume residual advanced disease ( suboptimal cytoreduction )
High risk for recurrence: 80-90% (  100%)
Thigpen JT, Clinical Ovarian Cancer 2008;1: 96-103

Ovarian Cancer: Early Stage Patients
Low Risk (Disease confined to 1 or 2 ovaries, with no risk factors)  No additional treatment
High risk  Chemotherapy
Paclitaxel + Carboplatin ( = Taxane + Platinum)
Taxane agents: Paclitaxel and docetaxel Platinum agents*: Carboplatin, Cisplatin Thigpen JT, Clinical Ovarian Cancer 2008;1: 96-103

Ovarian Cancer: Advanced Disease
Small volume residual advanced disease (optimal cytoreduction) &
Large volume residual advanced disease (suboptimal cytoreduction)
Both groups receive: Chemotherapy
Paclitaxel + Carboplatin ( = Taxane + Platinum)
80 % will respond to treatment and go on remission
75 % will recur
20 % will have chemoresistant disease and do poorly
Taxane agents: Paclitaxel and docetaxel Platinum agents: Carboplatin, Cisplatin

Ovarian Cancer: Small Volume Residual (Optimal), Advanced Disease Patients
Intraperitoneal (IP) Chemotherapy:
Delivery of chemotherapy to the abdominal cavity directly

Ovarian Cancer: Small Volume Residual (Optimal), Advanced Disease Patients
Intravenous (IV) & IP Paclitaxel and IP Cisplatin (GOG 172) versus IV Paclitaxel/Cisplatin
IP arm demonstrated the longest survival reported in the optimally debulked Stage III patients
16 months improvement: 65.6 months median survival vs 49.7 months
An improvement in Progression free survival (PFS): period of time that patients are alive without disease returning:
IV & IP Paclitaxel / IP Cisplatin: PFS: 23.8 months
IV Paclitaxel / IV Cisplatin: PFS 18.3 months
Armstrong DK et al. NEJM 2006. 354: 34-43

Trends in Five-year Relative Survival (%)* Rates, US, 1975-2003
All sites 50 54 66
Breast (female) 75 79 89
Colon 51 59 65
Leukemia 35 42 50
Lung and bronchus 13 13 16
Melanoma 82 87 92
Non-Hodgkin lymphoma 48 53 64
Ovary 37 40 45
Pancreas 2 3 5
Prostate 69 76 99
Rectum 49 57 66
Urinary bladder 74 78 81
* 5-year relative survival rates based on follow up of patients through 2004. Source: Surveillance, Epidemiology, and End Results Program, 1975-2004, Division of Cancer Control and Population Sciences, National Cancer Institute, 2007. Site 1975-1977 1984-1986 1996-2003

Recurrent Ovarian Cancer

Recurrent Ovarian Cancer
Patients free of disease 6 months or greater and then recur: Platinum sensitive. Options depend on:
amount of tumor that recurs - isolated versus multifocal
Can it be all removed surgically
functional status of patients - healthy versus unwell
For some: Surgery  chemotherapy (Platinum + Taxane) (Paclitaxel + Carboplatin)
Majority  Chemotherapy (Platinum + Taxane) (Paclitaxel + Carboplatin)
The response to the chemotherapy will be better the longer beyond 6 months that they were free of disease
Treat until progression, or unacceptable toxicity or complete response
If become resistant: change to a new drug, and repeat…
Patients free of disease less than 6 months and then recur: Platinum resistant.
Chemotherapy: Response rate is low (7-26 %)
Start with a nonplatinum single agent
Do poorly

Chemotherapy Agents Used in Recurrent Ovarian Cancer
carboplatin
cisplatin
pegylated liposomal doxorubicin
topotecan
gemcitabine
oral etoposide
vinorelbine
weekly paclitaxel
docetaxel
permetrexed
tamoxifen
oxaliplatin
5-fluorouracil

What’s new and hot: Targeted Therapies or Biologics!! agents that block a necessary pathway for cancer cells

What’s new and hot
Bevacizumab:

Future Directions

Future Directions in Advanced Ovarian Cancer GOG 212 GOG 252 Trying to find a more tolerable IP regimen Maintenance Chemotherapy

(Many agents being tested) :Better tolerated regimen, role of IP Carboplatin (Paclitaxel or bevacizumab)

Questions ??
Panel session for questions. Submit your questions.
Acknowledge & Thank: GynecoLogic Cancer Collaborative: Society of Gynecologic Oncologists (SGO): slides
Mildred R. Chernofsky, MD
Sibley Center for Gynecologic Oncology and Advanced Pelvic Surgery
202-243-5295

November 6-8, 2009
Washington, DC
Half marathon/5K /1 mile
walk
gcfrace.com
Free concurrent Survivor’s
Courses
Cervical Cancer,
Endometrial Cancer
Ovarian Cancer
To register:
http://www.wcn.org/courses/
CME Course for Physicians
To register:
www.sgo.org/content.aspx?id=2760

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Ovarian Cancer: Treatment Options after Diagnosis

by Sibley Memorial Hospital on Oct 12, 2009

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