Renal Pharmacology: Drugs for Renal Cancer

Question 1

What is the principal means of curing renal cancer?

Answer 1

Surgical excision.

Question 2

What are the common sites for metastatic growth of renal cancers?

Answer 2

(1) lymph nodes (most common)
(2) lung, liver, bones, (destructive lesions)
(3) Adrenal gland, Brain
(4) opposite kidney
(5) subcutaneous skin nodules.

Question 3

What is the general pattern of treatment for childhood tumors?

Answer 3

chemotherapy with VD, VDD, VDCE which have vincristine, dactinomycin, doxarubicin, cyclophosphamide, etoposide. If disease recurrs combinations with carboplatin, ifosfamide, cyclophosphamide are often used.

Question 4

What are the rapamycins?

Answer 4

Temsirolimus and everolimus.

Question 5

How do rapamycins function?

Answer 5

they bind to intracellular porteins then inhibit MTOR. This has immunosuppressant effects as well as inhibiting cell cycle progression and inducing cell apoptosis.

Question 6

How are the rapamycins administered?

Answer 6

temsirolimus is IV

Everolimus is oral

Question 7

How are the rapamycins metabolized?

Answer 7

They are both metabolized by CYP 3A4.

Question 8

What are the prominent side effects of the rapamycins?

Answer 8

30-50% of patients have

(1) maculopapular rash
(2) mucositis
(3) myelosuppression
(4) pulmonary infiltrates (less common 8%) (everolimus more than temsirolimus.)

Question 9

What class of drugs are sunitinib, sorafenib, and pazopanib?

Answer 9

They are all tyrosine kinase inhibitors.

Question 10

How to the TKIs function?

Answer 10

They bind and inhibit a variety of tyrosine kinases such as VEGF receptors and growth factor receptors.

Question 11

Which is the best antiangiogenic TKI?

Answer 11

sunitinib (30% response)

Question 12

How are the TKIs administered and metabolized?

Answer 12

The are given orally and are metabolized by CYP3A4.

Question 13

What are some common toxicities assocaited with the anti-angiogenic TKIs?

Answer 13

(1) bleeding
(2) HTN
(3) arterial thromboembolic events.

Question 14

What adverse effects are specific to sunitinib?

Answer 14

(1) fatigue
(2) hypothyroidism
(3) myelosuppression
(4) CHF
(5) Hand-foot syndrome.

Question 15

What adverse effects are specifically associated with pazopanib?

Answer 15

(1) hepatic disease (potentially fatal)

2) Hyperbilirubinemia (in Gilbert’s syndrome which is glucaronidation deficiency.

Question 16

What is the MOA of brevacizumab?

Answer 16

Brevacizumab directly inhibits VEGF. (works well in conjunction with INF-Alpha.)

Question 17

What adverse effects are associated with brevacizumab?

Answer 17

(1) HTN
(2) Thromboembolic events
(3) wound healing complications
(4) GI perforations
(5) proteinuria

Question 18

What is Aldesleukin?

Answer 18

Synthetic IL-2

Question 19

How does Aldesleukin work?

Answer 19

An orphan drug for renal cell carcinoma aldesleukin stimlulates the immune system to destroy the tumors. Exact mechanism is unknown.

Question 20

What adverse effects are associated with aldesleukin?

Answer 20

Very nasty stuff!

1) Capillary leak syndrome (leads to over 100 other adverse effects
(2) decrease in MAP may lead to death.

Question 21

How does INF-alpha work as a chemotherapeutic agent?

Answer 21

INF-Alpha has a direct anti-proliferative effect on tumor cells as well as stimulating the immune system to destroy tumor cells. Exact mechanisms are not clear.

Question 22

What adverse effects are associated with INF-alpha?

Answer 22

(1) neuro-psychiatric problems including suicidal tendencies.

Question 23

How beneficial is INF-alpha in treating renal cancer?

Answer 23

Study indicates that INF-alpha in conjunction with other therapies improves remission from 2.5% to 12.9% as opposed to other therapies alone.