Renal Malignancies

Question 1

Common sites for metastatic growth

Answer 1

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

Question 2

Childhood tumors

Answer 2

Wilm’s Tumor
Clear cell sarcoma
Rhabdoid and Neuroepithelial tumor

Question 3

Nephroblastoma

Answer 3

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

most commonly in children 3-4 yo

curable in majority of affected children

Question 4

Standard chemo for Wilm’s tumor postnephrectomy

Answer 4

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

Question 5

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

Answer 5

Vincristine, doxorubicin, and cyclophosphomide

Etoposide and cyclophosphamide

Question 6

Clear cell sarcoma: standard chemo

Answer 6

Either:

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

Question 7

Recurrent clear cell sarcoma

Answer 7

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

Question 8

Rhabdoid and Neuroepithelial tumor

Answer 8

no staisfactory therapy been discovered

Question 9

Route of administration for Childhood tumor treatments

Answer 9

IV

Question 10

Drugs for which childhood renal cancer is off label use

Answer 10

Carboplatin
Cyclophosphamide
Etoposide
Ifosfamide

Question 11

Carboplatin Toxicity

Answer 11

Myelosuppression; infection susceptibility

Question 12

Cyclophosphamide Toxicity

Answer 12

Myelosuppression: hemorrhagic cystitis (MESNA)

Question 13

DoxorubicinToxicity

Answer 13

Bone marrow suppression; acute and chronic cardiotoxicity

Question 14

Dactinomycin Toxicity

Answer 14

Myelosuppression; infection susceptibility

hepatic dysfunction

Question 15

Etoposide Toxicity

Answer 15

Hematologic toxicity

BP instability

Question 16

Ifosfamide toxicity

Answer 16

Bone marrow suppression
Hemorrhagic cystitis (MESNA)

Question 17

Vincristine toxicity

Answer 17

neurotoxicity; bilaterral sensory “stocking-glove” pattern

Question 18

Adult tumors

Answer 18

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

Question 19

Pts should receive single or combo therapy involving the following:

Answer 19

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

Question 20

The Rapamycins

Answer 20

Temsirolimus and Everolimus

Question 21

Rapamycins…MOA

Answer 21

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

Question 22

Rapamycins…Activity

Answer 22

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

Question 23

Temsirolimus administration

Answer 23

weekly IV

metabolized to sirolimus…prob the more important agent

Question 24

Everolimus administration

Answer 24

daily oral drug

Question 25

Rapamycins metabolized by

Answer 25

CYP 3A4

Question 26

Rapamycins...side effects

Answer 26

``` mild maculopapular rash mucositis anemia fatigue 30-50% of pts ``` Sometimes... reversible leukopenia or thrombocytopena pulmonary infiltrates (esp. w/ everolimus)

Question 27

TKIs

Answer 27

Sunitinib Sorafenib Pazopanib Inhibit VEGF-receptor + 2 other tyrosine kinases oral drugs metabolized by CYP3A4

Question 28

Response to sunitinib...

Answer 28

is better and longer lasting than for other antiangiogenic drugs

Question 29

Common vascular toxicities of antiangiogenic drugs

Answer 29

bleeding HTN arterial thromboembolic events

Question 30

Sunitinib specific side effects

Answer 30

``` fatigue hypothoyroidism bone marrow suppression CHF (often w/ HTN) Hand foot syndrome ```

Question 31

Pazopanib specific side effects

Answer 31

***Hepatic disease...severe and fatal hepatotoxicity!!! (needs monitoring) Hyperbilirubinemia...especially in gilbert's syndrome)

Question 32

VEGF-inhibitor

Answer 32

Bevacizumab (Avastin)

Question 33

Bevacizumab safety concerns

Answer 33

``` HTN inc incidence of arterial thromboembolic events wound healing complications GI perforations proteinuria fatigue ```

Question 34

Combo of bevacizumab w/ iterferon alfa

Answer 34

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

Question 35

Aldesleukin; IL-2

Answer 35

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

Question 36

Aldesleukin side effects

Answer 36

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

Question 37

Interferon-alpha (Roferon A)

Answer 37

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