Renal Pharmacology: Drugs for Renal Cancer Flashcards
What is the principal means of curing renal cancer?
Surgical excision.
What are the common sites for metastatic growth of renal cancers?
(1) lymph nodes (most common)
(2) lung, liver, bones, (destructive lesions)
(3) Adrenal gland, Brain
(4) opposite kidney
(5) subcutaneous skin nodules.
What is the general pattern of treatment for childhood tumors?
chemotherapy with VD, VDD, VDCE which have vincristine, dactinomycin, doxarubicin, cyclophosphamide, etoposide. If disease recurrs combinations with carboplatin, ifosfamide, cyclophosphamide are often used.
What are the rapamycins?
Temsirolimus and everolimus.
How do rapamycins function?
they bind to intracellular porteins then inhibit MTOR. This has immunosuppressant effects as well as inhibiting cell cycle progression and inducing cell apoptosis.
How are the rapamycins administered?
temsirolimus is IV
Everolimus is oral
How are the rapamycins metabolized?
They are both metabolized by CYP 3A4.
What are the prominent side effects of the rapamycins?
30-50% of patients have
(1) maculopapular rash
(2) mucositis
(3) myelosuppression
(4) pulmonary infiltrates (less common 8%) (everolimus more than temsirolimus.)
What class of drugs are sunitinib, sorafenib, and pazopanib?
They are all tyrosine kinase inhibitors.
How to the TKIs function?
They bind and inhibit a variety of tyrosine kinases such as VEGF receptors and growth factor receptors.
Which is the best antiangiogenic TKI?
sunitinib (30% response)
How are the TKIs administered and metabolized?
The are given orally and are metabolized by CYP3A4.
What are some common toxicities assocaited with the anti-angiogenic TKIs?
(1) bleeding
(2) HTN
(3) arterial thromboembolic events.
What adverse effects are specific to sunitinib?
(1) fatigue
(2) hypothyroidism
(3) myelosuppression
(4) CHF
(5) Hand-foot syndrome.
What adverse effects are specifically associated with pazopanib?
(1) hepatic disease (potentially fatal)
2) Hyperbilirubinemia (in Gilbert’s syndrome which is glucaronidation deficiency.
What is the MOA of brevacizumab?
Brevacizumab directly inhibits VEGF. (works well in conjunction with INF-Alpha.)
What adverse effects are associated with brevacizumab?
(1) HTN
(2) Thromboembolic events
(3) wound healing complications
(4) GI perforations
(5) proteinuria
What is Aldesleukin?
Synthetic IL-2
How does Aldesleukin work?
An orphan drug for renal cell carcinoma aldesleukin stimlulates the immune system to destroy the tumors. Exact mechanism is unknown.
What adverse effects are associated with aldesleukin?
Very nasty stuff!
1) Capillary leak syndrome (leads to over 100 other adverse effects
(2) decrease in MAP may lead to death.
How does INF-alpha work as a chemotherapeutic agent?
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.
What adverse effects are associated with INF-alpha?
(1) neuro-psychiatric problems including suicidal tendencies.
How beneficial is INF-alpha in treating renal cancer?
Study indicates that INF-alpha in conjunction with other therapies improves remission from 2.5% to 12.9% as opposed to other therapies alone.
