Flashcards in 15 Renal Cell Cancer Chan Deck (71):
What are some of the risk factors for Renal Cell Cancer?
Incidence increase age 55 and older. Gender: AA. Smoking and Obesity are the strongest links. Advanced kidney disease. HTN (increased secretion of renin by tumor). Strong family history
What are the strongest links to Renal Cell Cancer?
Smoking and Obesity
What is the hereditary risk factor with Renal Cell Cancer?
Von Hippel-Lindau (VHL) disease: rare, autosomal dominant genetic condition. Caused by mutations in the VHL gene. Patients often develop several kinds of tumors and cysts in different parts of the body. increased risk of CLEAR CELL cancer (seen often in younger patients)
What are the warning sings and symptoms in early stage?
Non-specific. Hematuria (60%), Flank mass (25%) - lower back or abdomen, Flank pain (40%)
What are the warning signs and symptoms in advanced stage?
Less common. Bone pain, adenopathy, pulmonary symptoms from lung metastases. Weight loss (30%), anemia (30%) d/t decreased erythropoietin production (i.e. fatigue). Swelling in legs and ankles
What is done in a renal cell cancer workup?
CT abdominal and pelvic, lung
What are the 5-year survival rates like for renal cell cancer?
Stage I (96%). Stage II (82%). Stage III (64%). Stage IV (23%)
What is required for a poor prognosis in renal cell cancer?
3 or more of these predictors. Lactage Dehydrogenase (LDH) > 1.5x ULN (good indication of proliferation). Corrected calcium level > 10. Hemoglobin < lower limit of NL. Initial diagnosis < 1 year to start of systemic therapy. 2 or more sites of metastases. Karnofsky performance score < 70 or ECOG > 2
What is screening like for renal cell cancer?
Currently NO reliable screening tests. Renal tumors - can be identified on imaging study (i.e. CT or ultrasound of abdomen/Pelvis)
What are some good prevention strategies for renal cell cancer?
Avoid smoking. Limit consumption of alcohol. Increase diet high in fruits and vegetables. Maintain healthy weight. Genetic testing/counseling - VHL gene mutation positive
How is the diagnosis and staging done for renal cell cancer?
Biopsy = ONLY mean to confirm diagnosis. Most common - fine needle aspiration biopsy (FNA) or core needle biopsy. A tumor with positive margins has higher recurrence rates
What do the different stages of renal cell cancer mean?
Stage I-II: Localized. Stage III: Invades peri-renal capsule and vena cava. Stage IV: LN+, mets to other organs
When is surgery (Partial Nephrectomy (Nephron-sparing surgery)) a treatment option for renal cell cancer?
Stage I, II, III (localized) with no involvement in major vessels or urine collecting system. Uninephric state (w/ fxn opposite kidney). Renal insufficiency. Bilateral renal masses. Familial RCC (VHL mutation)
When is surgery (Radical Nephrectomy) a treatment option for renal cell cancer?
Stage I, II, III (if partial nephrectomy is NOT indicated). Removal of kidney. Removal of perinephric fat outside of fascia. Regional nodal dissection (ipsilateral vessels and hilar nodes). +/- Adrenalectomy
What is the Adjuvant therapy (Stage I, II, III) option?
Provide individualized follow-up plan based on disease involvement (physical exam, labs, CT scan abdomen/lung, Chest X-ray, etc)
What is the recommended treatment option for Metastatic Stage IV renal cell cancer?
Cytoreductive nephrectomy prior to systemic therapy in patients with surgical resectable primary and multiple metastases
When is systemic therapy indicated in renal cell cancer?
Stage IV disease. Relapse of Stage I, II, or III disease. Surgically unresectable disease
What are the agents used for systemic therapy?
TKIs (Sunitinib, Sorafenib, Bevacizumab, Pazopanib). Temsirolimus (for poor prognosis patients). IL-2 (complete remission, high toxicity)
What are the second line systemic agents for renal cell cancer?
What is the brand of Sunitinib?
What is the brand of Sorafenib
What is the brand of Temsirolimus?
What is the brand of Bevacizumab?
What is the brand of Pazopanib?
What is the brand of Everolimus?
What is the brand of Axitinib?
What are the general characteristics of Cytokines (IL-2)?
High dose IL-2 (Proleukin) - High response rates and complete remission. OS 16 months
What is the MOA of Cytokines (IL-2)?
Immunotherapy: Promotes differentiation of T cells, B cells, NK cells and stimulates interactions between immune system and malignant cells
What is the administration of IL-2 like?
IVPB over 15 minutes Q8hrs for max of 14 doses (cycle repeat after 9 days) for a total of 28 doses
What is the compatibility of IL-2 like?
What are the ADRs associated with IL-2?
VERY TOXIC. Hypotension (require pressors, hold for SBP < 90), could be d/t capillary leak syndrome. CNS toxicities (severe lethargy and somnolence, hold AMS). Pulmonary toxicity (hold if O2 sat < 90%)
When is IL-2 indicated?
Reserved for patients with excellent performance status, low-volume lung involvement, normal organ function
What premeds can be used to help with IL-2 tolerability?
APAP (decreases fever), H2 antagonist (decreases GI irritation), Antiemetics, Antidiarrheal agents, Antibiotic prophylaxis
What is the MOA of IFN?
Cytokine. Immunotherapy. MOA: multiple and all in cellular level: interferes with oncogene expression. Alters cell surface antigen, increased cytotoxicity lymphocytes
What is OS like for IFN monotherapy?
What is OS like for IFN combination therapy?
18.3 months with Bevacizumab
What are the COMMON ADRs with IFN?
Flu-like syndrome, fatigue, anorexia, somnolence, transient increase in LFT, myelosuppression
What are the SEVERE ADRs with IFN?
Chest pain. Arrhythmias. Hypotension. Autoimmune disorder. Psychiatic disorders
What is dose-adjustment like with IFN?
Withhold treatment for ANC < 500 or platelets < 25,000
What are the two Immunotherapy agents used?
Cytokines (IL-2, IFN)
What is Temsirolimus (Torisel)?
Approved for treatment of ADVANCED RCC (OS 10.9 months)
What is Temsirolimus dosed?
25mg (FIXED DOSE) IV weekly, continue until disease progression or unacceptable toxicity
What is the MOA of Temsirolimus?
mTOR Kinase Inhibitor (downstream) - inhibits production of proteins that regulate cell cycle progression and angiogenesis
What labs need to be monitored while on Temsirolimus?
CBC w/ diff, CMP, Phosphate, LFTs (require dose adjustment), Lipid panel
What are the ADRs associated with Temsirolimus?
Infusion reactions. Increased Lipids. Increased Glucose. Decreased Phos and K. Increased SCr. Lymphopenia. Neutropenis. Anemia. Thrombocytopenia. Peripheral edema. Mucositis
When do you need to dose adjust Temsirolimus?
Hold if ANC < 1000 or platelets < 75k, decrease dose to 20mg weekly
What is Sorafenib (Nexavar)?
Approved for treatment of ADVANCED RCC (OS 19.3 months)
What is the MOA of Sorafenib (Nexavar)?
Multikinase and VEGFR inhibitor
When does Sorafenib (Nexavar) need to be dose adjusted?
Dose adjustment required if used concomitantly with CYP 3A4 inducers
What labs need to be monitored with Sorafenib (Nexavar)?
LFTs (require dose adjustment), SCr (Requires dose adjustment), CMP, CBC w/ diff, Phosphate
What are the COMMON ADRs with Sorafenib (Nexavar)?
Diarrhea. Fatigue. Lymphopenia, Neutropenia, Hand-foot syndrome, rash, stomatitis, increased INR, decreased Phos
What are the SEVERE ADRs with Sorafenib (Nexavar)?
Mild-moderate HTN, cardiac ischemia
What is Sunitinib (Sutent)?
Approved for treatment of ADVANCED RCC (OS 26.4 months)
What is the MOA of Sunitinib (Sutent)?
Multikinase (PDGFR, VEGFR inhibitors; stem cell factor receptor (c-KIT); FMS-like TK (FL3)
What needs to be monitored while on Sunitinib (Sutent)?
LFTs, CBC w/ diff, CMP, CV (blood pressure, decreased LVEF, increased QTc)
When does Sunitinib (Sutent) need to be dose adjusted?
Adjustment required if use concomitantly with CYP 3A4 inhibitors/inducers. Renal adjustment not needed for SCr < 2. Liver adjustment not needed for mild-moderate increase in LFTs
What are the common ADRs with Sunitinib (Sutent)?
Similar to other TKIs
What are the SEVERE ADRs with Sunitinib (Sutent)?
Hypothyroidism. Neutropenia. Thrombocytopenia. Bleeding
What patient education should be done with Sunitinib (Sutent)?
Skin and/or hair depigmentation or discoloration
What is Pazopanib (Votrient)?
Approved for treatment of ADVANCED RCC (OS 9.2 months)
What is the MOA of Pazopanib (Votrient)?
Multikinase and VEGFR inhibitor
When does Pazopanib (Votrient) need to be dose adjusted?
Required if used concomitantly with CYP 3A4 inhibitors/inducers
What needs to be monitored while on Pazopanib (Votrient)?
LFTs (require dose adjustment), CMP, Mag, CV, UA, thyroid function test, CBC w/ diff
What patient education needs to be done with Pazopanib (Votrient)?
Hair color changes
What is Everolimus (Afinitor)?
Approved for 2nd line treatment of ADVANCED RCC (after failure with Sorafenib or Sunitinib)
What is the MOA of Everolimus (Afinitor)?
Macrolide immunosuppressant and an m-TOR Kinase inhibitor, decreases VEGF and hypoxia-HIF-1 expression
When does Everolimus (Afinitor) need dose adjustment?
If used concomitantly with CYP 3A4 inhibitors/inducers. With increased LFTs (monitor)
What is some patient education for Everolimus (Afinitor)?
Take with or without food, if unable to swallow, disperse completely in 30mL water with gentle stirring; rinse container with additional 30mL water and swallow. Avoid contact with or exposure to crushed or broken tablets
What is Axitinib (Inlyta)?
Approved for 2nd line treatment of advanced RCC (after failure with one prior systemic therapy with cytokines or Sunitinib)
What is the MOA of Axitinib (Inlyta)?
Multi-kinase inhibitor and VEGFR inhibitors