Pharmacology Of Renal Neoplasia

Question 1

Kidney and renal cancer facts

Answer 1

6th most common cancer in men; 8th most common in women

Commonly diagnosed in 40-70s

Risk factors
- smoking 
- obesity 
- untreated HTN (especially if >150/90) 
Family history 

85% = renal call carcinomas
- most common subtype = clear cell

Question 2

Clincial presentation of renal cancers

Answer 2

Classic triad (although only 10% present with this)

• flank pain
• hematuria
• palpable mass that cross midline

Question 3

Staging of kidney cancers and overall survival %

Answer 3

Stage 1:

• only found in kidney
• low grade
• is less than 7cm in diameter
• 5 yr% = 96

Stage 2:

• only found in kidney
• low-mid grade
• > 7cm in diameter
• 5 yr% = 82

Stage 3: 
 Has spread to near by structures and surrounding fat (however has NOT crossed Geroat’s fascia) 
- mid-high grade 
- can be any size 
- 5 yr % = 64 

Stage 4:

• has spread past geroat’s fascia and is often metastatic to lungs and brain tissues
• high grade
• can be any size
• 5 yr% = 23

Question 4

What are the most common metastasis sites for kidney cancers (renal cell carcinomas)?

Answer 4

Lung

Bone

Liver

Brain

Question 5

Goals of therapy for RCC

Answer 5

Stage 1-3

• nephrectomy (+/-) chemo
• • 20-30% of patinets will release though within 2 yrs so need to monitor aggressively

Stage 4

• palliative care (+/-) aggressive chemo
• focus more on quality of life

Question 6

How is chemotherapy divided in kidney cancer patients?

Answer 6

Based on whether it is clear cell histology on biopsy or not

Question 7

Why does gemcitabine, vinblastine and 5-FU have such poor efficacy in RCC?

Answer 7

Due to very high levels of P-glycoprotein being present especially in RCC cases
- this protein functions as an energy dependent pump towards chemotherapy agents and other toxins

This induces drug resistance and is a product of up-regulation of the MDR1 gene

Question 8

What is capillary leak syndorme

Answer 8

Rare disorder that can occur idiopathically or via drug exposure (usually biologics)

Casues capillary fenestrations to widen greatly, leading to hypotension, hypoalbuminemia, hemoconcentrations

Leads ultimately if untreated to overwhelming edema and shock levels of hypotension and stoppage of breathing

must try to catch this if it starts to present since its highly fatal

Question 9

What are the first generation TK Inhibitors used in RCC?

Answer 9

Sunitinib

Sorafenib
- 2nd line in noval mRCC. Hardly used for refractory or advanced mRCC

Pazopanib

sunitinib and pazopanib are first line agents in noval mRCC and 2nd line in advanced or refractory

Question 10

What is the 2nd generation TK- inhibtor used for mRCC?

Answer 10

Axitinib

50-450x more potent and is first line in both noval mRCC and advanced/refractory mRCC

Question 11

What is the hallmark for clear cell RCC?

Answer 11

Inactivation of VHL suppressor gene

Question 12

What are the first line therapy options of mRCC non advanced?

Answer 12

Temisrolimus IV = only for high risk mRCC

Sunitinib, pazopanib and axitinib are the 1st line TK-Inhibitors

Question 13

What are 2nd line agents reserved for only advanced mRCC/ refractory mRCC

Answer 13

Sorafenib and carbozantinib and everolimus