Drugs to Treat Ovarian and Bladder Cancer

Question 1

What is the most important risk factor for Epithelial Ovarian Carcinoma?

Answer 1

Cancer in a 1st degree relative

Question 2

For Ovarian Cancer limited to the ovary and peritoneum, what drug can be administered intraperitoneally?
- advantages?

Answer 2

• *High Volume Cisplatin Instillation**
• allows for high drug concentration without systemic toxicity

Question 3

What Drugs (4 or 5 of them) are used in treatment of ovarian cancer? 
\*\*What drug should be included for more advanced cancers?

Answer 3

Platinum Drug + Cyclophosphamide or Doxorubicin or Paclitaxel

More advanced cancers require Paclitaxel

Question 4

What is the most common presenting symptom in bladder cancer?

Answer 4

Hematuria

Question 5

BCG

• Administration
• MOA
• Indication

Answer 5

BCG (Bacillus-Calmette-Guerin)
ADMINISTRATION
Intravesicular

MOA
Binding to Urothelial cells attracts APCs that present cancer cell antigens to Lymphocytes, NK cells, ect that will learn to recognize cancer cell antigens

INDICATION
Bladder Cancer

Question 6

What abnormal histology might be seen in bladder cancer if it has been treated with BCG?

Answer 6

**Could see granulomas in the bladder of someone treated with BCG for bladder cancer**

Question 7

Carboplatin

• MOA
• AEs

Answer 7

MOA:
- Forms DNA intrAstrand crosslinks and adducts

AE:

• Allergic (platinum) rxns, dose-related myelo-suppression, cumulative anemia, BLOOD DYSCRASIA, N/V.
• Increased Hepatic Enzymes, BUN and Creatinine
• Oto/Nephro/Neurotoxic, but not to the extent of cisplatin

*Indicated for the treatment of bladder cancer

Question 8

Cisplatin

• MOA
• AEs

Answer 8

Cisplatin:
- forms DNA intrAstrand crosslinks and adducts

AEs:

• Allegeric (platinum) rxns, Dose-related SEVERE (dose-limiting) nephrotoxicity, myelosuppression, N/V.
• OTOTOXICY, Nephropathy

Indicated for tx of bladder CA

Question 9

Cyclophosphamide

• MOA
• AEs

Answer 9

Cyclophosphamide
MOA:
- Pro-drug of active alkylating moiety

Indication:
- Renal Compromise, HEMORRHAGIC CYSTITIS (give mesna), Amenorrhea, infertitlity, Pulmonary Fibrosis

Question 10

Doxorubicin
MOA
AEs

Answer 10

Doxorubicin
MOA
- Intercalator, free radical generator, topo II inhibitor (etoposide is also a topo II inhibitor, the tecans inhibit topo I)

AEs
- myelosuppression, CHF (dilated cardiomyopathy), Hepatic disease, secondary malignancy, extravasational necrosis

Question 11

Mitomycin C

• MOA
• AEs

Answer 11

Mitomycin C
MOA
- Mono and Bi-functional alkylating agent

AEs
- Pancytopenia, CHEMICAL CYSTITIS (along with cyclophosphamide), Contact dermititis, PALMAR and PLANTAR erythema IF contact made with sol’n DIRECTLY or IN URINE

Question 12

Paclitaxel
MOA
AEs

Answer 12

MOA
Stabilizes microtubues and prevents the cell from exiting M-phase

AEs
Neuropathy

Question 13

Thiotepa

• MOA
• AEs

Answer 13

Thiotepa
MOA
- Polyfunctional alkylator with loss of aziridine (alkylator) moeity

AEs
- Dysuria, Urinary Retention, Chemical/Hemorrhagic Cystitis, Renal Dysfunctoin

Question 14

What drug are often administered intravesicularly in bladder cancer?

Answer 14

Mitomycin C
Thiotepa
BCG

Question 15

What 3 drugs used to treat bladder CA cause hemorrhagic cystitis?

Answer 15

Cyclophosphamide
Mitomycin C
Thiotepa

Question 16

What drug that is commonly administered intravesicularly is likely to have systemic effects despite the route of administration?
- Why?

Answer 16

Thiotepa is a LOW MW drug and thus can diffuse through urothelial tissue and have systemic effects

Question 17

NOTE - all of these drugs damage the integrity of the bladder to some extent giving them a greater chance of going systemic

Answer 17

NOTE - all of these drugs damage the integrity of the bladder to some extent giving them a greater chance of going systemic

Question 18

What two drugs used to treat bladder cancer have the potential to cause pulmonary fibrosis and unproductive cought?
- what unique side effect could differentiate these two?

Answer 18

Both Mitomycin C and Cyclophosphamide could do this.
Mitomycin C has the unique effect of cause erythema when it comes into contact with skin