Ovarian Cancer Flashcards
Ovarian Cancer
- Leading cause of death in the US from gynecologic malignancies
- Peak incidence is ~ __ years of age
– Lifetime risk is 1 in ___
- 65
- 72
Etiology and Pathogenesis
exact cause unknown
The “incessant ___ ” theory
– A women’s risk of developing ovarian cancer is related to her ___ of ovulatory cycles
– Ovulation results in disruption and repair of the epithelial lining of the ovaries
– The ___ of the lining is proposed as one origin of sporadic ovarian cancer
- ovulation
- number
- repair
Etiology
- Germ line mutations are responsible for ~ 5 - 10% of all ovarian cancers
- Lifetime risk of ovarian cancer in a patient with a ___ mutation is 25 - 45%
- Lifetime risk of ovarian cancer in a patient with a ___ mutation is up to 30%
- 5 to 10% of patients have hereditary non- polyposis colorectal cancer (HNPCC) or other rare genetic syndromes
- BRCA1
- BRCA2
Risk Factors
- Early menarche, late menopause
- (increased number and/or duration of ___ cycles)
– Increased ___
– Nulliparity
– ___ fertilization (Use of ovulatory stimulating agent can ↑ the
number of ovulatory cycles)
– Two or more first degree relatives with ovarian cancer - Genetic factors: ___, ___have ↑’d risk for development of ovarian cancer
- Lynch II syndrome (Hereditary nonpolyposis colorectal cancer (HNPCC)
- ovulatory
- age
- in-vitro p53
- BRCA,
Decreased Risk
- Multiple ___
- Prolonged use of ___ - > 50% ↓ after 5 years of use
- Prophylactic ___
- pregnancies
- oral
- oophoretomy
Clinical Presentation: “Silent Killer”
- Most patients with Stage I and II disease are asymptomatic
- Leads to the unfortunate result of most patients presenting with ___ disease (stage III and IV) - 70%
advanced
- In advanced disease symptoms could include: ascites, pleural effusion, constipation, small bowel obstruction, nausea or vomiting
Initial Treatment
Most patients will achieve a clinical
complete remission to initial treatment
* However, 70-90% of patients will recur in the first 3 years
Initial treatment approach:
– Goal is ___
– Surgery + adjuvant chemotherapy is standard approach first line (neoadjuvant?)
– With relapse any therapy is ___
Should have genetic risk evaluation, germline and somatic testing in all patients to help decide ___ therapy; in absence of BRCA mutations, ___ ___ ___ (HRD) may help determine therapy
- cure
- palliative
- maintenance
- homologous recombination deficiency
Homologous Recombination Deficiency (HRD)
50% high-grade serous ovarian carcinomas are homologous recombination deficient
- Defect in one or more genes involved in homologous ___ pathway
- Includes germline and somatic ___ pathogenic variants
- repair
- BRCA
Treatment Overview
0) ± neoadjuvant platinum-based
chemotherapy
1) Surgical staging and debulking
2) Adjuvant platinum-based chemotherapy
3) Frontline maintenance therapy
4) Relapse
5) Recurrence therapy
6) Maintenance therapy of recurrence
Surgery
“Debulking” Surgery generally entails:
* Total abdominal hysterectomy (TAH)
* Bilateral salpingo-oophrectomy (BSO)
* Omentectomy
* Pelvic and para-aortic lymph node sampling
* Peritoneal biopsies
* Peritoneal washings
Surgical Outcomes
- Optimally debulked: < 1 cm of disease
- Sub-optimally debulked: > 1 cm of disease remaining
Patients that have a sub-optimally debulked surgery have a poorer prognosis
Adjuvant Chemotherapy
Stage IA or IB grade 1 disease
* Observation and follow up every 3 months
All other stages should receive adjuvant chemotherapy. Standard of care:
- ___ and ___
- Paclitaxel
- Carboplatin
Adjuvant Chemotherapy
Most patients will receive 6 cycles of
chemotherapy
Carboplatin dosing:
– Elimination of carboplatin closely mirrors GFR
Calvert equation:
* Carboplatin dose = AUC x (GFR + 25)
The AUC is usually __ - __ if given every 3 weeks
5 -7.5
Hypersensitivity Reactions
- Agents commonly used are paclitaxel, docetaxel, carboplatin, and cisplatin
- All agents are known culprits to causing hypersensitivity reactions
- Exposure to multiple cycles of chemotherapy (i.e., > 7) ___ risk of carboplatin hypersensitivity reactions
increases
Type I Hypersensitivity
___ contact with agent
* Mechanism: Cross linking to mast cells and basophils which trigger release of histamine and other inflammatory mediators
* Symptoms: ___ , itching, rash, chest tightness
- initial
- Anaphylaxis
Type IV Hypersensitivity
With ___ exposure to agent
- Mechanism: T-cells recognize antigens (MHC, APC)
* Symptoms: ___ , induration
- repeated
- Erythema
Common Chemotherapy Culprits
Allergic to the drug itself
- Carboplatin
- Cisplatin
- Docetaxel
- Paclitaxel
- Rare: Etoposide, topotecan
- NEED ___
- Symptoms ___ after
stopping infusion
Often Infusion Related Reactions
- Paclitaxel – ___ EL
- Doxil - liposome
- Decreasing ___ ___typically resolves symptoms
- Symptoms ___ quickly after
stopping infusion
- DESENSITIZATION
- persist
- cremophor
- infusion rate
- resolve
Paclitaxel
- Most manifest as a Type __ reaction
- Most reactions occur within the first few ___ of the infusion with the first or second dose
- Believed to be due to the ___ diluent as opposed to the chemotherapy
- Type I
- minutes
- Cremophor EL
Taxane Infusion Reactions
- Likely a result of direct effects on immune cells
- Usually occurs during ___ or ___ exposure
Most common reactions to paclitaxel
- Facial flushing
- Back pain
- Chest or throat tightness
The risk of having a recurrent reaction ___ with repeated exposures
- 1st, 2nd
- decreases
Paclitaxel: Ways to Avoid Problems
Standard pre-medications
- ___ , ___ , and ___ 30 minutes prior
- ___ infusion may resolve
symptoms
- Always when administering, should have an ___ kit at bedside
- dexamethasone, diphenhydramine, famotidine
- prolonging
- anaphylactic
Carboplatin Hypersensitivity
Hypersensitivity to platinum agents generally develops after ___ cycles of treatment
- Peak incidence of hypersensitivity reactions to carboplatin occurs at a median of __ cycles
Most common symptoms
– Cutaneous symptoms
– Vomiting
– Hypotension
- multiple
- 7
Carboplatin
Mechanism could be 2-fold
- Type I: Drug/antigen specific IgE’s that have high binding affinity to receptors on mast cells and basophil
- Type IV: Delayed hypersensitivity reaction occurring when antigen sensitized cells release cytokines after subsequent contact
- ___ exposures (≥ __ cycles of carboplatin) increased risk of hypersensitivity reactions
repeated, 8
Maintenance Bevacizumab?
- Bevacizumab recommended in those that received bevacizumab with chemotherapy upfront prior to surgery to continue as monotherapy
- Not recommended in those with ___ mutations
BRCA
PARP Inhibitors
MOA: prevents the
PARP protein from repairing damaged DNA in cancer cells
Three agents approved in ovarian cancer:
– Olaparib (Lynparza)
– Rucaparib (Rubraca)
– Niraparib (Zejula)
PARP inhibitors
monitoring parameters
- Olaparib: CBC, ___ function
- Niraparib: CBC, __, HR
- Rucaparib: CBC, ___ (if warfarin cant be avoided)
AE
- N/V, fatigue, anemia, neutropenia, thrombocytopenia
- renal
- BP
- INR
Metastatic Disease
- Ultimately, 60 - 80% of pts will relapse
- The goal is no longer ___
- Decisions about therapy should include toxicity, regimen, and convenience of administration, and quality of life
- No standard therapy for recurrent disease
- cure
Recurrence Definitions
if the pt relapses > 6 months following completion of their initial platinum containing regimen, the patient is “Platinum ___ ”
- May be treated with the ___ chemotherapy regimen again
If the patient relapses < 6 months after
receiving a platinum containing regimen, the patient is considered “Platinum ___ ”
- a ___ regimen is generally chosen
Platinum ___ : (Platinum refractory)
- No response or progression of disease during primary therapy with ___ / ___
- sensitive
- initial
- resistant, salvage
- progressive
- paclitaxel/carboplatin
Recurrence Definitions
If the patient is platinum sensitive, re-use ___ / ___ combination
paclitaxel/carboplatin
Treatment Regimens
Single agent non-
platinum based if
platinum resistant:
