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Renal Pharm > Rx of Renal Cancer > Flashcards

Rx of Renal Cancer Flashcards

(48 cards)

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1
Q

What is the principal means of producing a cure in renal cancer?

A

thru surgical excision

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2
Q

What are the 4 situations in the treatment of renal cancer when chemotherapy/radiotherapy drugs would be employed?

A
  1. With advanced stage/grade
  2. If the tumor has metastasized
  3. As an adjunctive therapy with surgery/radiation
  4. As a primary therapy where medical circumstances preclude surgery
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3
Q

What are common sites for renal tumor metastasis (5)? What is the most common? Where does a renal tumor metastasis cause destructive lesions?

A
  1. Lymph nodes (most common)
  2. Lung Liver Bone (destructive lesions)
  3. Adrenal Gland, Brain
  4. Opposite kidney
  5. Subcutaneous skin nodules
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4
Q

What are the three types of childhood renal tumors? Which is most common?

A
  1. Nephroblastoma (WIlm’s Tumor)→most common
  2. Clear Cell Sarcoma
  3. Rhabdoid and Neuroepithelial Tumor
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5
Q

In what age group is nephroblastoma (Wilm’s) most common? What is the prognosis and 5-yr survival rate?

A

children age 3-4; curable in the majority of children; 5-yr survival rate above 90% (not as high for clear cell sarcoma)

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6
Q

What is standard therapy for nephroblastoma?

A

Nephrectomy followed by a 1.5-2 yr regimen of a combo containing Vincristine + Dactinomycin and/or Doxorubicin +/- others.

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7
Q

Treatment of recurrent nephroblastoma involves what?

A

Alternating courses of 1. Vincristine + Doxorubicin + Cyclophosphamide and 2. Etoposide + Cyclophosphamide

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8
Q

Standard chemotherapy of Clear Cell Sarcoma (CCSK)?

A

Combo of components of nephroblastoma tx and RADIATION THERAPY

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9
Q

Tx of recurrent CCSK?

A

initially carboplatin and cyclophosphamide (CC=CC)

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10
Q

Patients with recurrent CCSK involving the brain respond to what treatment?

A

ICE (ifosfamide, carboplatin, and etoposide) with either surgery or radiation

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11
Q

What is the standard therapy for Rhabdoid and Neuroepithelial tumors?

A

No satisfactory therapy has been discovered

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12
Q

Toxicities of Carboplatin?

A

myelosuppresion; infection susceptibility; ototoxicity, nephrotoxicity

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13
Q

Toxicity of Cyclophosphamide?

A

Myelosuppresion; Hemorrhagic Cystitis→MESNA

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14
Q

Toxicity of Doxorubicin?

A

Bone marrow suppression; acute and chronic CARDIOTOXICITY

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15
Q

Toxicity of Dactinomycin?

A

Myelosuppression; HEPATIC dysfunction; infection susceptibility

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16
Q

Toxicity of Etoposide?

A

Hematologic toxicity; BP INSTABILITY

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17
Q

Toxicity of Ifosfamide?

A

bone marrow suppression; Hemorrhagic Cystitis→MESNA

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18
Q

Toxicity of Vincristine?

A

Neurotoxicity; bilateral sensory “stocking glove pattern→peripheral neuropathy

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19
Q

How do adult renal tumors respond to cytotoxic therapy? What has this led to?

A

responses to cytotoxic therapy generally have not exceeded 10% for any traditional drug regimen. So, now patients receive a single of combination therapy of the drugs listed in the table on p. 3

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20
Q

What are the two Rapamycin drugs?

Study These Flashcards
A

Temsirolimus and Everolimus

21
Q

What is the mechanism of action of the Rapamycins? What does this result in?

Study These Flashcards
A

They bind to FKBP12 and inhibit mTORC1, which causes:

  1. Immunosuppressant effects
  2. Inhibition of cell-cycle progression
  3. Promotion of apoptosis
22
Q

What may be responsible for incomplete responses or resistance to rapamycins?

Study These Flashcards
A

Resistance may arise thru the action of a second unaffected mTOR complex, which regulates AKT Kinase

23
Q

How does Temsirolimus therapy of renal cancer compare to standard IFN-alpha therapy?

Study These Flashcards
A

Temsirolimus prolongs survival and delays progression in patients with advanced and poor- or intermediate-risk renal cancer, compared to standard IFN-alpha treatment.

24
Q

Everolimus prolongs survival in what kind of renal cancer patients?

Study These Flashcards
A

those who had failed initial treatment with anti-angiogenic drugs (sunitinib and/or sorafenib)

25
How are temsirolimus and everolimus taken?
Temsir→weekly, IV | Ever→daily, oral
26
Temsirolimus is metabolized to what?
Sirolimus, likely the more important agent
27
Why are temsirolimus and everolimus susceptible to drug-drug interactions?
bc both are CYP3A4 substrates
28
What are prominent side effects of the rapamycins? (4) Minor side effects?
each occurs in 30-50% of patients: maculopapular rash, mucositis, anemia, and fatigue Minor: reversible thrombocytopenia and leukopenia
29
What potential side effect of rapamycins results in the need to discontinue them? Which rapamycin is more commonly associated with this? What are the signs that this is happening?
In 8% of Everolimus patients (and smaller percentage of temsirolimus pts) PULMONARY INFILTRATES emerge with symptoms such as SOB, or radiological changes→drug should be discontinued
30
What drug is used to treat the pulmonary infiltrate that may emerge in a patient on rapamycins?
Prednisone
31
Which anticancer drug is a recombinant form of IL-2? What was is designated as?
Aldesleukinn (proluekin); it was designated as an orphan drug for renal cell carcinoma.
32
What is the mechanism of action of Aldesleukin?
It interacts with the high-affinity IL-2 receptor on cells of the immune system→stimulates a cytokine cascade of IFNs, ILs, and TNFs→activation of cytotoxic lymphocytes
33
What is the potentially very serious consequence of Aldesleukin that is responsible for most of its 126 listed adverse effects?
Very nasty stuff: CAPILLARY LEAK SYNDROME: extravasation of plasma proteins and fluid into the extravascular space leading to loss of vascular tone→Reduced Mean Arterial Pressure
34
What is the potential result of Capillary leak syndrome in pt's on Aldesleukin?
Decreased MAP and organ perfusion may be severe and can result in DEATH
35
What are the TKIs used to treat renal cancers? (3)
1. Sunitinib 2. Sorafenib 3. Pazopanib
36
What is the mechanism of action of all three of these TKIs?
Anti-angiogenic: They all inhibit VEGF-receptor-2 and at least two other tyrosine kinases: blocking the major transduction pathways activated by these receptor tyrosine kinases
37
How does response to sunitinib compare to that of other antiangiogenic drugs?
Response to sunitinib is better (31%) and longer lasting than for other anti-angiogenic drugs.
38
Sunitinib, Sorafenib, and Pazopanib are all metabolized by what?
CYP3A4
39
What are the common toxicities of these anti-angiogenic drugs?
Vascular Toxicities: | 1. Bleeding 2. HTN 3. Arterial thromboembolic events
40
What are the Sunitinib-specific side effects? (5)
1. Fatigue 2. Hypothyroidism 3.Bone Marrow Suppression 4. CHF (often w/ HTN) 5. Hand-foot syndrome
41
What is the major Pazopanib-specific side effect? What does this require of the physician when giving this to the patient?
HEPATIC DISEASE: severe and fatal hepatotoxicity. | Have to monitor serum liver function tests
42
Which TKI can cause Hyperbilirubinemia, especially in Gilbert's syndrome (glucuronidation deficiency; reduced excretion of bilirubin)?
Pazopanib
43
What is Bevacizumab?
VEGF-inhibitor
44
What are the main safety concerns with bevacizumab? (6)
HTN, increased incidence of arterial thromboembolic events (TIA, stroke, angina, MI), wound-healing complications, GI perforations, proteinuria, fatigue
45
Which of the following treatments results in a significantly improved survival in patients with metastatic renal cell carcinoma: a) Bevacizumab+IFN-alpha b) IFN-alpha alone
Bevacizumab + IFN-alpha
46
How does IFN-alpha work? (2)
1. Direct and indirect anti-proliferative effects on tumor cells by a) enhancing or inhibiting the synthesis of specific proteins b) modifying cell surface antigen expression which modulates the immune system In other words, it induces a host response to the tumor (immunomodulatory effects) and exerts a cytostatic effect on tumor cells, slowing the rate of cell proliferation until tumor cell survival is threatened.
47
What are the very serious side effects associated with IFN-alpha?
Life threatening or fatal neuropsychiatric events, including: suicide, homicidal or suicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior even in patients without previous psychiatric disorders
48
What offers the best prospect for remission of advanced renal cell cancer?
Targeted Therapy, but even this approach has only limited success

Renal Pharm (4 decks)

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