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HEME PHARM > Renal Malignancies > Flashcards

Renal Malignancies Flashcards

1
Q

Common sites for metastatic growth

A 
Lymph nodes (most common)
Lung, Liver, Bone (destructive lesions)
Adrenal gland
Brain
Opposite kidney
Subcutaneous skin nodules
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2
Q

Childhood tumors

A

Wilm’s Tumor
Clear cell sarcoma
Rhabdoid and Neuroepithelial tumor

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3
Q

Nephroblastoma

A

(Wilm’s Tumor)
most common renal tumor in children

most commonly in children 3-4 yo

curable in majority of affected children

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4
Q

Standard chemo for Wilm’s tumor postnephrectomy

A
  • -Vincristine, dactinomycin x 18 wks
  • -Vincristine, dactinomycin, doxorubicine x 24 wks
  • -Vincristine, doxorubicin, cyclophosphamide, etoposide x 24 wks
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5
Q

Recurrent disease (Wilm’s tumor) involves alternating cources of:

A

Vincristine, doxorubicin, and cyclophosphomide

Etoposide and cyclophosphamide

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6
Q

Clear cell sarcoma: standard chemo

A

Either:

  • -Vincristine, dactinomycin, and doxorubicin for 15 mo and radiation
  • -vincristine, doxorubicin, cyclophosphamide and etoposide and radiation
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7
Q

Recurrent clear cell sarcoma

A

cyclphosphamide and carboplatin if not used initally
pts w/ recurrent CCSK involving brain respond to ifosfamide, carboplatin and etoposide (ICE) coupled w/ local control consisting of either surgical resection and/or radiation

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8
Q

Rhabdoid and Neuroepithelial tumor

A

no staisfactory therapy been discovered

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9
Q

Route of administration for Childhood tumor treatments

A

IV

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10
Q

Drugs for which childhood renal cancer is off label use

A

Carboplatin
Cyclophosphamide
Etoposide
Ifosfamide

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11
Q

Carboplatin Toxicity

A

Myelosuppression; infection susceptibility

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12
Q

Cyclophosphamide Toxicity

A

Myelosuppression: hemorrhagic cystitis (MESNA)

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13
Q

DoxorubicinToxicity

A

Bone marrow suppression; acute and chronic cardiotoxicity

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14
Q

Dactinomycin Toxicity

A

Myelosuppression; infection susceptibility

hepatic dysfunction

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15
Q

Etoposide Toxicity

A

Hematologic toxicity

BP instability

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16
Q

Ifosfamide toxicity

A 
Bone marrow suppression
Hemorrhagic cystitis (MESNA)
17
Q

Vincristine toxicity

A

neurotoxicity; bilaterral sensory “stocking-glove” pattern

18
Q

Adult tumors

A

responses to cytotoxic chemo generally have not exceeded 10% for any “traditional” drug regimen

19
Q

Pts should receive single or combo therapy involving the following:

A 
Aldesleukin; IL-2
Bevacizumab w/ or w/out interferon-alpha
Everolimus (for pts who've been previously treated w/ sunitinib and/or sorafenib)
Interferon-alpha
Pazopanib
Sorafenib
Sunitinib
Temsirolius
20
Q

The Rapamycins

A

Temsirolimus and Everolimus

21
Q

Rapamycins…MOA

A

bind to FKBP 12 and inhibit mTORC1
–immunosuppressant effects
–inhibition of cell-cycle progression and angiogenesis
–promotion of apoptosis
Resistance incompletely understood but may arise through action of second mTOR complex
–may be responsible for incomplete responses or resistance of rapamycins

22
Q

Rapamycins…Activity

A

Temsirolimus prolongs survival and delays disease progression in pts w/ advanced and poor or intermediate risk renal cancer

Everolimus prolongs survival in pts who had failed intial treatment w/ anti-angiogenic drugs

23
Q

Temsirolimus administration

A

weekly IV

metabolized to sirolimus…prob the more important agent

24
Q

Everolimus administration

A

daily oral drug

25
Q

Rapamycins metabolized by

A

CYP 3A4

26
Q

Rapamycins…side effects

A 
mild maculopapular rash
mucositis
anemia
fatigue
30-50% of pts

Sometimes…
reversible leukopenia or thrombocytopena
pulmonary infiltrates (esp. w/ everolimus)

27
Q

TKIs

A

Sunitinib
Sorafenib
Pazopanib

Inhibit VEGF-receptor + 2 other tyrosine kinases

oral drugs metabolized by CYP3A4

28
Q

Response to sunitinib…

A

is better and longer lasting than for other antiangiogenic drugs

29
Q

Common vascular toxicities of antiangiogenic drugs

A

bleeding
HTN
arterial thromboembolic events

30
Q

Sunitinib specific side effects

A 
fatigue
hypothoyroidism
bone marrow suppression
CHF (often w/ HTN)
Hand foot syndrome
31
Q

Pazopanib specific side effects

A

***Hepatic disease…severe and fatal hepatotoxicity!!! (needs monitoring)

Hyperbilirubinemia…especially in gilbert’s syndrome)

32
Q

VEGF-inhibitor

A

Bevacizumab (Avastin)

33
Q

Bevacizumab safety concerns

A 
HTN
inc incidence of arterial thromboembolic events
wound healing complications
GI perforations
proteinuria
fatigue
34
Q

Combo of bevacizumab w/ iterferon alfa

A

first-line treatment in pts w/ metastatic renal cell carcinoma…significant improvement in progression-free survival compared w/ interferon alfa alone

35
Q

Aldesleukin; IL-2

A

recombinant form of IL-2
Orphan drug for renal cell carcinoma
–stimulates cytokine cascade involving various interferons, interleukins, TNF
Antitumor activity believed to result from activation of cytotoxic lymphocytes

36
Q

Aldesleukin side effects

A

VERY NASTY STUFF
capillary leak syndrome
Decreased MAP and decreased organ perfusion
Many many more adverse effects

37
Q

Interferon-alpha (Roferon A)

A
  • -Direct antiproliferative effect on tumor cell
  • -Induction of host response to tumor (immunomodulatory effects)
  • -Life-threatening or fatal neuropsychiatric events

HEME PHARM (10 decks)

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