Describe epithelial ovarian carcinomas
This is a common gynecologic malignancy with risk factors including fam hx of similar cancers in 1st degree relatives and BRCA1/2 mutations
What serum marker is commonly used to measure EOC progression/proliferation?
How are EOCs staged?
By confinement to the ovaries or lack of
E.g. Stage I is confined to 1 or both ovaries, Stage II is spread to other areas of the pelvis, Stage III is spread to nearby lymph nodes, and Stage IV is mets to lung, liver, bone, and as pleural effusion
What are the treatment options of EOC?
May involve a combo of surgery (bilateral salpingo-oophorectomy), radiation, and chemo
What chemo drugs are commonly used in EOC Tx?
Commonly a platinum drug in combo with cyclophosphamide, doxorubicin, or paclitaxel. For advanced disease, these are given IV but for local disease pts receive a 1-2L instilled volume of drugs that is retained up to 2 hrs then drained off to ensure adeuqate coverage of peritoneal surfaces
Describe the progression of bladder cancer?
Bladder cancer begins in the cells lining the urothelial surface, the ones that are in frequent contact with carcinogenic substances (especially in smokers!!). With progression of the tumor, there is increased penetration through the lamina propria into the underlying muscle, and the potential of mets
What is the most common presenting symptom of bladder carcinoma?
How is superficial bladder cancer treated?
trans-urethral resection of the cancer, often followed by intravesicle instillation of a high conc of chemo drugs. Where the tumor progresses, chemo-radiation is employed, and possibly cystectomy if needed.
What are the most common chemo drugs used for intravesical instillation?
mitomycin and BCG
How does BCG instillation work?
It binds to urothelial cells, attracts APCs,a nd ultimately leads to production of a host of immune system effector cells, including CTLs and NKs. This immune response can be detected within hrs and persist for days
How do Carboplatin and Cisplatin work?
They form DNA intrastrand crosslinks and adducts
How does cyclophosphamide work?
It is a pro-drug of active alkylating moiety
How does doxorubicin work?
It is an intercalator, free radical generator, and topo II inhibitor
How does Mitomycin C work?
What is Thiotepa?
Thiotepa is a small molecular weight drug that can pentrate urothelial tissue that forms by forming DNA intrastrand cross-links via diethylenethiophosphoramide after metabolic hydrolysis cleaves aziridine.
What are the AEs of Carboplatin?
Allergic rxns; Dose-related myelosuppression
Dose-related N/V, dyscrasia, and hepatic and renal dysfunction
What are the AEs of Cisplatin?
Allergic rxns; Dose-related nephrotoxicity, myelosuppression, and N/V
Significant ototoxicity in children
What are the AEs of Cyclophosphamide?
What are the AEs of Doxorubicin?
What are the AEs of Mitomycin C?
Pancytopenias when used IV
chemical cystitis, contact dermatitis but also as palmar and plantar erythemas if contact is made with instillate solution or voided volume
pulmonary infiltrates with dyspnea and unproductive cough
What are the AEs of Paclitaxel?
taxane hypersensitivity, myelosuppression, myalgia and arthralgia
What are the AEs of Thiotepa?
pancytopenia (when used IV)- dose limiting
dysuria, urinary retention, chemical/hemorrhagic cystitis and renal dysfunction