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Repro > Sweatman - Ovarian/Bladder Cancer > Flashcards

Sweatman - Ovarian/Bladder Cancer Flashcards

1
Q

What is one of the potential problems with the “belly bath” approach?

A

Potential for drug systematization

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2
Q

What intervention may be necessary to improve QOL in pts with ovarian cancer?

A
  • Some patients with ovarian cancer will develop massive ascites
  • May need to have fluid drawn off to INC QOL
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3
Q

Why may be carboplatin be preferred over cisplatin in some cases?

A
  • Produces less peripheral neuropathy (but also MORE myelosuppresion)
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4
Q

What is a unique drug admin method for the bladder? Special considerations?

A
  • Because this is an organ of containment, you can put a catheter in, and put drugs into it
  • These drugs will, however, be absorbed into the circulation -> concentration and molecular weight important
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5
Q

What drugs can be used to treat ovarian cancer (table)?

A
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6
Q

What drugs can be used to tx bladder cancer (table)?

A
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7
Q

What is the epi of the epithelial ovarian carcinoma? Risk factors? Prevention?

A
  • 5th most freq cause of cancer death in women
    1. Hereditary patterns: ovarian cancer alone, ovarian and breast, ovarian and colon
    2. Most important risk factor: family history of first degree relative
  • BRCA1/2 germline muts INC risk
  • Prophylactic oophorectomy considered after age 35 if childbearing complete
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8
Q

How can we monitor epi ovarian carcinoma?

A
  • Serum CA (cancer antigen)-125 levels: secondary measure of tumor activity and progression, and also drug effectiveness
  • Protein level elevated in most ovarian cancer cells
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9
Q

What are the stages of epi ovarian carcinoma?

A
  • Stage 1: confined to 1 or both ovaries
  • Stage 2: 1 or both ovaries, and spread to other areas of the pelvis
  • Stage 3: spread to other parts of abdomen, and/or nearby lymph nodes
  • Stage 4: mets to lymph nodes, liver, lung, bone, and as pleural effusion
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10
Q

How might later stage epi ovarian carcinoma present?

A
  • For peritoneally confined disease, and with mets, pt may present w/peritoneal and/or pleural ascites
  • May require frequent drainage and make life uncomfortable for end-stage pts
  • Some pts may elect to receive IP drug instillations in a palliative mode to DEC rate of build-up of ascites
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11
Q

How is epi ovarian carcinoma treated?

A
  • May involve a combo of:
    1. Surgery: bilateral salpingo-oophorectomy or debulking
    2. Radiation: external and instilled P32
    3. Chemo
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12
Q

What are the chemo options for epi ovarian carcinoma?

A
  • High-volume intra-peritoneal cisplatin instillation: solution instilled (1-2L), retained for up to 2 hrs, then drained off (supine pt rotates from side-to-side)
    1. Allows higher doses and more freq admin; appears to be more effective
    2. For locally confined disease
  • Adjuvant IV admin of conventional agents (systemic; for more advanced disease)
    1. S1&2: carboplatin- or cisplatin-based regimen, usually w/cyclophosphamide and/or doxorubicin
    2. S3&4: carboplatin- or cisplatin with paclitaxel may be superior to cyclophos
  • NOTE: biologics and targeted therapies under investigation, but none has received approval yet
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13
Q

What is the staging for bladder carcinoma? Why?

A
  • Progression of original tumor from urothelial surface to underlying structures allows for escape from original organ of confinement
    1. INC penetration through lamina propria into the underlying muscle
  • NOTE: begins with transformation of cells lining the urothelial surface bc they remain in contact with high concentrations of chemicals, some of which are carcinogenic (i.e., smokers)
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14
Q

What is the epi of bladder cancer? Presenting symptom?

A
  • 7th most common cancer in men
  • 70% transitional cell carcinoma
  • 70% superficial on presentation: hematuria is common presenting symptom
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15
Q

How is bladder cancer treated?

A
  • Non-muscle invasive:
    1. Trans-urethral resection (TUR) of superficial disease and regular cystoscopy to monitor for recurrence or progression
    2. Intravesicular (IVe) instillation mitomycin C
    3. >1 yr of IVe Bacillus Calmette-Guerin (BCG)
    4. Add’l IVe drugs for high-risk pts (thiotepa)
  • Chemo-radiation or _systemic chemo_therapy
  • Cystectomy: if bladder-sparing techniques prove inadequate
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16
Q

BCG admin? How does it work?

A
  • Used after TURBT and in tx of CIS: 50 mL instillation held for 1-2hr, 6x/week
    1. Good response rates for prophylaxis, CIS, and eradication of residual disease
  • Activity requires an intact immune system:
    1. Binds urothelial cells and activates APCs
    2. Induces production of effector cells: CTLs, NKs, LAKs, and BAKs
    3. Peak response in 6-24 hrs, INC w/successive cycles (lasts for days)
    4. Sustained effect over months: rationale for maintenance, “booster” tx (short, periodic cycles) -> no universally accepted schedule
17
Q

What is the MOA of carboplatin/cisplatin?

A

Form DNA intrastrand crosslinks and adducts

18
Q

What is the MOA of cyclophosphamide?

A

Pro-drug of alkylating moiety

19
Q

What is the MOA of Doxorubicin?

A
  • Interacalator
  • Free radical generator
  • Topo II inhibitor
20
Q

What is the MOA of Mitomycin C?

A

Mono- and bifunctional alkylating agent

21
Q

What is the MOA of Paclitaxel?

A

Microtubule stabilizer inhibiting depolymerization

22
Q

What is the MOA of Thiotepa? What is unique about this drug for bladder cancer tx?

A
  • MOA: polyfunctional alkylator w/loss of aziridine (alkylator produced by metabolic hydrolysis from thiotepa, which has 3 aziridine groups) moiety
    1. Remaining moiety, diethylenethiophosphor-amide forms DNA interstrand cross-links
  • Lipophilic small molecular weight drug that can penetrate easily into urothelial tissue, which has been the source of some systemic toxicities due to the unique nature of this drug vs. the others that are instilled IVe
23
Q

How might IVe drugs penetrate the bladder wall?

A
  • TUR damages the integrity of the bladder containment
  • Depending on the extent and depth of penetration, this can compromise the retention of the drug in the bladder lumen, and significantly INC the potential for drug systematization
24
Q

What are the issues with Carboplatin?

A
  • Allergic (platinum) reactions
  • Dose-related myelosuppression; cumulative anemia
  • Dose-related N/V
  • Blood chemistry dyscrasia
  • INC hepatic enzymes, BUN, and creatinine
25
Q

What are the issues with Cisplatin?

A
  • Allergic (platinum) reactions
  • Dose-related severe nephrotoxicity, myelosuppression, and N/V
  • Significant ototoxicity: tinnitus, and occasionally deafness reported in CHILDREN
  • Peripheral neuropathy
26
Q

What are the issues with Cyclophosphamide?

A
  • Blood dyscrasias -> anemia, infection
  • Renal compromise
  • N/V, rashes
  • Hemorrhagic cystitis (mesna is protective)
  • Amenorrhea, infertility
  • Monitor for 2o malignancies
  • Pulmonary fibrosis
27
Q

What are the issues with Doxorubicin?

A
  • Myelosuppression
  • CHF
  • Hepatic disease
  • 2o malignancies
  • Extravasational necrosis
  • N/V
28
Q

What are the issues for Mitomycin C?

A
  • IV: pancytopenia
  • IVe: chemical cystitis
    1. Contact dermatitis, but also as palmar and plantar erythemas if contact made with instillate solution or void volume
  • Also capable of producing pulmonary infiltrates, with dyspnea and unproductive cough
29
Q

What are the issues with Paclitaxel?

A
  • Taxane hypersensitivity
  • Myelosuppression
  • Myalgia and arthralgia
  • Peripheral neuropathy
30
Q

What are the issues with Thiotepa?

A
  • IV: pancytopenia
  • IVe: dysuria (painful or difficult urination), urinary retention
    1. Chemical/hemorrhagic cystitis
    2. Renal dysfunction
31
Q

Are biomarkers used in the tx of bladder cancer?

A
  • Yes!
  • Don’t need to memorize these yet though bc no therapeutic decisions made based on this data yet
  • This will change -> potential for targeted therapy

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