Therapeutics of Ovarian Cancer (Weddle) Flashcards
Explain the “incessant ovulation” theory.
That ovarian cancer risk is related to number of ovulatory cycles
List some risk factors for ovarian cancer.
- early menarche, late menopause
- increased age
- nulliparity
- in vitro fertilization
- 2+ 1st degree relatives with ovarian cancer
- BRCA1/2, p53
- Lynch II syndrome (HNPCC)
- Caucasian
What are some factors that decrease risk of ovarian cancer?
- multiple pregnancies
- prolonged oral contraceptive use
- prophylactic oophorectomy
___________________ represents > 90% of ovarian cancer cases.
epithelial adenocarcinoma
What are the five subtypes of ovarian cancer?
- serous
- endometrioid
- mucinous
- clear cell (worse prognosis)
- sex cord stromal tumors
What is the current screening tool for ovarian cancer?
there is no effective screening tool
How should women at low risk for ovarian cancer be screened?
annual physical and pelvic exam
How should women at high risk for ovarian cancer be screened?
pelvic exam, transvaginal ultrasound, and CA-125 blood test every 6-12 months (starting age 25-35)
Why do most ovarian cancer patients tend to present with advanced-stage disease?
because stage I and II are typically asymptomatic
What symptoms may present with advanced ovarian cancer?
- ascites
- pleural effusion
- constipation
- small bowel obstruction
- nausea/vomiting
What is involved in a diagnostic work-up for ovarian cancer?
- H&P
- pap smear
- transvaginal ultrasound
- abdominal CT, chest x-ray
- colonoscopy
- CBC, serum chemistries, CA-125
- exploratory laparotomy
How is ovarian cancer staged?
surgically
What is the standard, 1st line approach to treating ovarian cancer?
surgery + adjuvant therapy
What does it mean if a patient is classified as “optimally debulked”?
< 1 cm of disease remaining
What does it mean if a patient is classified as “sub-optimally debulked”?
> 1 cm of disease remaining
Which stage of ovarian cancer does not need adjuvant chemotherapy?
IA/IB grade 1; just observe and follow-up every 3 months
What is the current standard of adjuvant chemotherapy for ovarian cancer?
paclitaxel and carboplatin every 3 weeks
Elimination of carboplatin closely mirrors ___________.
GFR
Why is the GYN/ONC cancer population extra susceptible to hypersensitivity reactions?
chemotherapeutic agents used (paclitaxel, docetaxel, carboplatin, cisplatin) and exposure to multiple chemotherapy cycles
What is a type I hypersensitivity?
occurs with initial contact
What is the mechanism of type I hypersensitivity?
cross-linking to mast cells and basophils which trigger release of histamine and other inflammatory mediators
What is a type II hypersensitivity?
occurs with repeated exposure to an agent
What is the mechanism of type II hypersensitivity?
T-cells recognize antigens
What symptoms are associated with type I hypersensitivity?
anaphylaxis, itching, rash, chest tightness
What symptoms are associated with type II hypersensitivity?
erythema, induration (infusional type reactions)
Which chemo hypersensitivity culprits are actually often infusion-related reactions?
paclitaxel (Cremophor) and liposomal doxorubicin
List some common symptoms of infusion-related toxicity.
- flushing
- redness
- tingling
- headache
- shortness of breath
- abdominal/chest pain
Most paclitaxel hypersensitivity reactions manifest as type __.
I
What are the three standard pre-medications that can be used to avoid hypersensitivity reactions to paclitaxel?
- dexamethasone
- diphenhydramine
- famotidine
Carboplatin hypersensitivity can best be described as type IV. What is type IV?
delayed reaction occuring when antigen-sensitized cells release cytokines after subsequent contact
What are the two aims of intraperitoneal chemotherapy for stage IIIC ovarian cancer?
increased tumor exposure and decreased systemic toxicity
Patients with tumors ______ cm tend to respond best to intraperitoneal chemotherapy.
< 2
What qualifications make a patient a good candidate for intraperitoneal chemotherapy?
- stage III
- good performance status
- normal renal function
- no previous problems that could worsen during chemo (i.e., preexisting neuropathy)
- no hx of bowel surgery/resection
What toxicities are prevalent in ovarian cancer patients treated with adjuvant bevacizumab therapy?
hypertension and GI perforations
Give an example of a PARP inhibitor.
olaparib, rucaparib, niraparib
Which PARP inhibitor should be used as maintenance after 1st line chemo for germline or somatic BRCA mutations?
olaparib (Lynparza)
Which PARP inhibitor should be used as maintenance after 1st line chemo in patients regardless of BRCA status?
niraparib (Zejula)
What are the two most common toxicities amongst all PARP inhibitors?
fatigue, anemia (also N/V)
What does it mean when a patient is platinum sensitive?
they have relapsed > 6 months following completion of their initial platinum-containing regimen
What are the treatment options for a platinum sensitive patient?
can be treated with the initial chemo regimen again; re-use paclitaxel/carboplatin
What does it mean when a patient is platinum resistant?
the patient has relapsed < 6 months after receiving a platinum-containing regimen
What does it mean if a patient is platinum progressive/refractory?
they have shown no response/progression of disease during primary therapy with paclitaxel/carboplatin
