Ovarian Cancer

Question 1

What is etiology of Ovarian Cancer?

Answer 1

• Cause unknown
• Mutations [BRAC 1 =25-45%; BRAC 2 = 30%]

Question 2

What is the pathogenesis of Ovarian Cancer?

Answer 2

• “Incessant Ovulation” - number of ovulatory cycles that results in disruption and repair of the epithelial lining

Question 3

What are some of the risk factors for Ovarian Cancer?

Answer 3

• # of ovulatory cycles
• Age
• Kids?
• Genetics [BRAC 1 & 2]

Question 4

What are some of the the ways that we could decrease the risk factors for Ovarian Cancer?

Answer 4

• Multiple pregnanies
• ORAL contraceptives
• Oophorectomy [remove ovaries]

Question 5

Why is Ovarian Cancer known as the “Silent Killer”?

Answer 5

• Stage I and II is asymptomatic - DONT KNOW THEY HAVE IT
• Leading to advanced disease [70%]

Question 6

What are some of the Clinical Presentations for Ovarian Cancer?

Answer 6

• Bloating, Fatigue, Indigestion, Increased Urination, Pelvic Pain, constipation
• Lasting more than 12 or more days of a month for 2 months GO TO DOCTOR

Question 7

What is the initial treatment that should be used in Ovarian Cancer?

Answer 7

• CURE
• Surgery + Adjuvant Chemo [70-90% will recur]

Question 8

What are some thing that should be done to help with determining Ovarian Cancer Treatment?

Answer 8

• Genetic Evalution
• BRCA or HRD can help determine

Question 9

What is Homologous Recombination Deficiency within Ovarian Cancer?

Answer 9

• 50% of ovarian carcinomas - defect in one or more genes

Question 10

What is the treatment overview for Ovarian Cacner?

Answer 10

• +/- neoadjuvant platinums
• Surgery or not [ALWAYS A ROLE]
• Adjuvant platinums
• Maintenance [PARPs]
• RELAPSE [restart chemo]
• recurrent therapy
• Maintenance [PARPs]

Question 11

What is important to know about Surgery in Ovarian Cancer?

Answer 11

• “Debunking” - removing as much cancerous tissue from the abdomen to < 1cm [OPTIMAL]
• Sub-optimal = > 1cm

Question 12

What is adjuvant chemotherapy for Ovarian Cancer?

Answer 12

• NOT in stage I or II [observation]
• ALL OTHER STAGES [Paciltaxel x3h + Carboplatin x21d]

Question 13

What is the way that we determine the Carboplatin dosing in Adjuvant Chemo for Ovarian Cancer?

Answer 13

• Calvert Equation = AUC x (GFR + 25)
• AUC ~ 5-7.5

Question 14

What are some of the most common agents to cause Hypersensitivity reactions in Ovarian Cancer?

Answer 14

• PACLITAXEL [Cremophor], docetaxel, carboplatin, cisplatin
• NEED DESENSITIZATION [slowly infuse drug]

Question 15

What is Type I Hypersensitivity in Ovarian Cancer?

Answer 15

• immediate response to drug
• Anaphylaxis, Itching, rash, chest tightness

Question 16

What Type IV Hypersensitivity in Ovarian Cancer?

Answer 16

• Repeated exposure to the drug - T cells recognize antigens
• Erythema [skin redness], Induration [thicken soft tissue]

Question 17

What is important to know about Paclitaxel in Hypersensitivity in Ovarian Cancer?

Answer 17

• COMMON - 30% [Type I]
• Due to Cremophor

Question 18

What is important to know about the Taxane Infusion Reactions in Hypersensitivity in Ovarian Cancer?

Answer 18

• Direct effect on immune cells during the 1st or 2nd exposure
• Flushing, Back Pain, Chest tightness

Question 19

What are some of the ways that we are able to avoid the problems with Paclitaxel in Ovarian Cancer?

Answer 19

• Steroid + H1 + H2
• Dexamethasone + Diphenhydramine + Famotidine [Anaphylactic Kit]

Question 20

What is important to know about Docetaxel and Albumin Bound Paclitaxel reaction in Ovarian Cancer?

Answer 20

• Docetaxe: Polysorbate 80
• Albumin Bound Paclitaxel: Human Albumin

Question 21

What is important to know about Carboplatin Hypersensitivity in Ovarian Cancer?

Answer 21

• Occurs after multiple cycles - 7 CYCLE [Type IV]
• Can cause vomiting, hypotension

Question 22

What can be used as maintenance therapy in Ovarian Cancer?

Answer 22

• Bevacizumab or PARP Inhibitors

Question 23

What is important to know about PARP inhibitors in Ovarian Cancer?

Answer 23

• MOA: Forms double strand DNA breaks in BRCA cells and prevents DNA repair = cell death
• OlaPARib, RucePARib, NiraPARib

Question 24

What is PARP?

Answer 24

• Helps repair the Single and Double Stranded DNA breaks [can increase Cancer survival]
• PARP Inhibitors STOP repair

Question 25

What PARP inhibitors are used for Maintenacne after platinum respone? What are used in Recurrent Ovarian Cancer?

Answer 25

• Platinum: Olaparib [BRCA] & Niraparib [No BRCA]
• Recurrent: Olaparib [No BRCA], Niraparib [BRCA], Rucaparib [BRCA]

Question 26

What are some of the important monitoring parameters for PARP inhibitors in Ovarian Cancer?

Answer 26

• CBC monitoring & Renal Function [Olaparib]

Question 27

What are some of the adverse effects in PARP inhibitors in Ovarian Cancer?

Answer 27

• Anemia, Neutropenia, Thrombocytopenia

Question 28

What is important to know aobut Metastatic Ovarian Cancer?

Answer 28

• NO LONGER CURE
• no standard of therapy

Question 29

What is Recurrence within Ovarian Cancer?

Answer 29

• Relapses > 6 months following completion = “Platinum Sensitive” [can use plats again]
• Relapses < 6 months following platinums = “Platinum Resistant” [never responded]

Question 30

What is the treatment for the recurrences in Ovarian Cancer?

Answer 30

• Sensitive: Paclitaxel/Carboplatin again
• Resistant: Non-Platinums [Cyclophophamide, Docetaxel…]
• Clinical trails

Question 31

EXAMPLE: What is the 1st line chemotherapy for someone with Stage III Ovarian Cancer?

Answer 31

• Paclitaxel + Carboplatin x6 cycles
• Surgery

Question 32

EXAMPLE: What would be the 1st choice for treatment for recurrent Ovarian Cancer?

Answer 32

• WHEN?
• > 6 = same chemo [Paclitaxel + Carboplatin]
• <6 = Switch to non-platinum agent

Question 33

EXAMPLE: What is the role of maintenance therapy in Ovarian Cancer?

Answer 33

• PARP Inhibitors
• Olaparib [BRCA] or Narapinib [NO BRCA] –> Chemo –> Maintenance with PARP