Download Slide 1

Common Urologic Agents Used in the GU
Cancer Patient
Jay Simhan, MD
March 2012
Bladder Cancer
Vinblastine
• Mechanism of Action: Inhibits assembly of
microtubules and arrests cells in metaphase
• Half-life: 24 hrs
• Primary clinical toxicity:
– Alopecia
– Parethesias
– HTN
– Myelosuppression
• Primary lab effect: Neutropenia
• Monitoring of Treatment: CBC, BMP, LFTs,
Serum Uric Acid
Methotrexate
• Mechanism of Action: Inhibits metabolism of
folic acid
• Half-life: 10 hrs
• Primary clinical toxicity:
– Ulcerative stomatitis
– CNS toxicity
• Primary lab effect: Neutropenia
• Monitoring of Treatment: CBC, BMP, LFTs,
Serum Uric Acid
Adriamycin (Doxorubicin)
• Mechanism of Action: Intercalates DNA
• Half-life: 3.5 hrs
• Primary clinical toxicity:
– Nausea
– Vomiting
– Heart Arrhythmias
• Primary lab effect: Neutropenia
• Monitoring of Treatment: CBC, BMP, LFTs,
cardiac exam (baseline)
Cisplatin
• Mechanism of Action: DNA alkylating agent
• Half-life: 1 hrs
• Primary clinical toxicity:
– Nephrotoxicity
– Neurotoxicity
– Nausea, vomiting
– Ototoxicity
• Primary lab effect: Cr clearance,
hypomagnesemia, hypocalcemia
• Monitoring of Treatment: CBC, BMP, LFTs,
U/A, Audiography
Carboplatin
• Mechanism of Action: DNA alkylating agent
• Half-life: 6 hrs
• Primary clinical toxicity:
– Myelosuppression
– Nausea/Vomiting
– Nephrotoxicity (at high doses)
• Primary lab effect: Neutropenia, anemia, Cr
(at high dosese)
• Monitoring of Treatment: CBC, BMP, LFTs
Gemcitabine
• Mechanism of Action: DNA analogue
replaces cytidine in DNA replication,
arresting cell cycle
• Half-life: 10 hrs
• Primary clinical toxicity:
– Muscle pain,
– Fever, chills, fatigue
– Headache
• Primary lab effect: LFT elevation, proteinuria
• Monitoring of Treatment: CBC, BMP, LFTs
BCG
• Mechanism of Action: Live attenuated
mycobacteria, induces local inflammatory
and granulomatous reaction
• Half-life: unknown
• Primary clinical toxicity:
– Dysuria
– Urinary urgency
– Fever
• Monitoring of Treatment: Flu like
syndrome/fever> 3days, CBC, BMP, LFTs
Mitomycin C
• Mechanism of Action: Antitumor antibiotic
activity
• Half-life: 1 hour
• Primary clinical toxicity:
– Bone marrow suppression (w/ long term use)
– Lung fibrosis
– Renal damage
• Primary lab effect: Anemia
• Monitoring of Treatment: CBC, BMP, PT, PFTs
Interferon
• Mechanism of Action: Protein that acts on
oncogenes to induce cell death
• Half-life: 5 hours
• Primary clinical toxicity:
– Bone marrow suppression
– Flu like syndrome
– Cardiovascular effects
• Primary lab effect: LFT elevation
• Monitoring of Treatment: CBC, BMP, LFTs
Testis Cancer
Bleomycin
• Mechanism of Action: Inhibits synthesis of DNA by
binding DNA and inducing strand breaks
• Half-life: 9 hours
• Primary clinical toxicity:
– Pulmonary fibrosis
– Alopecia
– Hepatotoxicity
– Chills/Fever
• Primary lab effect: LFT elevation
• Monitoring of Treatment: CBC, BMP, LFTs, PFTs,
CXR
Ifosfaminde
• Mechanism of Action: Cross links DNA
causing synthesis inhibition
• Half-life: 15 hours
• Primary clinical toxicity:
– Bone marrow suppression
– CNS toxicity
– Hemorrhagic cystitis
• Primary lab effect: Metabolic acidosis,
hyperbilirubinemia, AKI
• Monitoring of Treatment: CBC, BMP, LFTs
Etoposide
• Mechanism of Action: Delays transit of cells
through S phase; topoisomerase II inhibitor
• Half-life: 8 hours
• Primary clinical toxicity:
– Bone marrow suppression
– Hypersensitivity reactions
– Hypotension
• Primary lab effect: Neutropenia, LFT
elevation
• Monitoring of Treatment: CBC, BMP, LFTs
Kidney Cancer
Sunitinib
• Mechanism of Action: VEGF inhibitor
• Half-life: 2 days
• Primary clinical toxicity:
– HTN
– Fatigue
– Hand-foot syndrome
– Nausea
• Primary lab effect: LFT elevation, CK
elevation, AKI
• Monitoring of Treatment: CBC, BMP, LFTs,
TFTs, U/A, Echo (assessing LV EF)
Pazopanib
• Mechanism of Action: VEGF inhibitor
• Half-life: 31 hrs
• Primary clinical toxicity:
– HTN
– Hair color change
– Diarrhea, fatigue
• Primary lab effect: LFT elevation
• Monitoring of Treatment: CBC, LFTs, TFTs,
U/A, blood pressure
Sorafenib
• Mechanism of Action: Multikinase inhibitor,
including VEGF, RAF kinase, cKIT, RET
• Half-life: 1-2 days
• Primary clinical toxicity:
– Hand-foot syndrome
– HTN
– Complications from wound healing
• Primary lab effect: Leukopenia, elevates INR,
hypoalbuminemia
• Monitoring of Treatment: CBC, BMP,
amylase, lipase, TFTs
Bevacizumab
• Mechanism of Action: VEGF inhibitor
• Half-life: 20 days
• Primary clinical toxicity:
– GI organ perforation
– HTN
– Complications from wound healing
• Primary lab effect: Proteinuria
• Monitoring of Treatment: CBC, blood
pressure, urine dipstick for proteinuria
Temsirolimus
• Mechanism of Action: mTOR inhibitor – reduces
HIF proteins and VEGF
• Half-life: 17 hours
• Primary clinical toxicity:
– Rash
– Mucositis
– Nausea
– Dyspnea
• Primary lab effect: hyperlipidemia, hyperglycemia
• Monitoring of Treatment: CBC, BMP, LFTs, lipid
panel
Erlotinib
• Mechanism of Action: EGFR inhibitor
• Half-life: 1-2 days
• Primary clinical toxicity:
– Fatigue
– Rash
– Diarrhea
– Dyspnea
• Primary lab effect: LFT elevation, renal failure
• Monitoring of Treatment: LFTs, BMP
Everolimus
• Mechanism of Action: mTOR inhibitor
• Half-life: 30 hrs
• Primary clinical toxicity:
– Stomatitis
– URI
– Rash
– Fatigue
• Primary lab effect: LFT elevation, anemia,
hypercholesterolemia
• Monitoring of Treatment: CBC, BMP, LFTs,
lipid panel
IL-2
• Mechanism of Action: Proliferation of immune
cells causing interaction w/malignant cells and
subsequent cell death
• Half-life: 2 hrs
• Primary clinical toxicity:
– Hypotension (capillary leak syndrome)
– Chills, diarrhea
– Oliguria, dyspnea
• Primary lab effect: AKI, LFT elevation,
thrombocytopenia
• Monitoring of Treatment: CBC, BMP, LFTs, CXR,
PFTs, ABG, Thallium stress test
Prostate Cancer
Bicalutamide
• Mechanism of Action: Antiandrogen,
competitive inhibitor for binding of DHT and
testosterone
• Half-life: 6 days
• Primary clinical toxicity:
– Hot flashes
– Pain
– Constipation
• Primary lab effect: LFT increase
• Monitoring of Treatment: CBC, LFTs, EKG,
testosterone, PSA
Flutamide
• Mechanism of Action: Antiandrogen, inhibits
androgen uptake or binding of androgen in
target tissue
• Half-life: 6 hours
• Primary clinical toxicity:
– Gynecomastia
– Nausea/vomiting
– Galactorrhea
• Primary lab effect: LFT increase, anemia
• Monitoring of Treatment: LFTs,
testosterone/estrogen, phosphatase
Nilutamide
• Mechanism of Action: Antiandrogen, blocks
testosterone effects at the androgen level
• Half-life: 3 days
• Primary clinical toxicity:
– Hot flashes
– Nausea
• Primary lab effect: LFT increase
• Monitoring of Treatment: LFTs, CXR
Ketoconazole
• Mechanism of Action: Inhibits androgen
synthesis
• Half-life: 8 hours
• Primary clinical toxicity:
– Nausea/vomiting
• Primary lab effect: LFT increase
• Monitoring of Treatment: LFTs
Cyproterone
• Mechanism of Action: Antiandrogen, blocks DHT to
prostate cancer cells and release of LH from
pituitary
• Half-life: 4 days
• Primary clinical toxicity:
– Edema
– Dry skin
– Chills
• Primary lab effect: LFT increase, anemia, adrenal
suppression
• Monitoring of Treatment: CBC, BMP, LFTs, adrenal
function
Abiraterone
• Mechanism of Action: Selectively and
irreversibly inhibits CYP17 (lyase), enzyme
required for androgen synthesis
• Half-life: 12 hours
• Primary clinical toxicity:
– Edema
– Diarrhea
– Joint swelling
• Primary lab effect: Triglyceride increase,
hypokalemia, LFT increase
• Monitoring of Treatment: LFTs
Docetaxel
• Mechanism of Action: Promotes assembly of
microtubules resulting in inhibition of DNA,
RNA, and protein synthesis
• Half-life: 11 hours
• Primary clinical toxicity:
– Fluid retention
– Alopecia
– Stomatitis
• Primary lab effect: Neutropenia, LFT increase
• Monitoring of Treatment: CBC, BMP, LFTs
Leuprolide
• Mechanism of Action: LHRH agonist
• Half-life: 3 hours
• Primary clinical toxicity:
– Hot flashes
– Headache
– Nausea/vomiting
• Primary lab effect: Increased creatinine
• Monitoring of Treatment: LH and FSH levels,
testosterone, PSA
Goserelin
• Mechanism of Action: LHRH agonist
• Half-life: 4 hours
• Primary clinical toxicity:
– Hot flashes
– Sexual dysfunction
• Primary lab effect: Increased lipids
• Monitoring of Treatment: Bone mineral
density, calcium, lipid panel
Degarelix
• Mechanism of Action: GnRH antagonist
• Half-life: 53 days
• Primary clinical toxicity:
– Hot flashes
• Primary lab effect: Increased lipids, LFT
increase
• Monitoring of Treatment: Testosterone, PSA,
BMP, LFTs
Mitoxantrone
• Mechanism of Action: Intercalates DNA
resulting in cross-linking and strand breaks
• Half-life: 3 days
• Primary clinical toxicity:
– Fever
– Alopecia
– Nausea
– Weakness
• Primary lab effect: Neutropenia, LFT increase
• Monitoring of Treatment: CBC, LFTs
Sipuleucel-T
• Mechanism of Action: Immunotherapy that
induces immune response against prostate
cancer cells
• Half-life: Unknown
• Primary clinical toxicity:
– Chills
– Nausea
– Back pain
– Infusion reaction
• Primary lab effect: Anemia
• Monitoring of Treatment: CBC, BMP
Cabazitaxel
• Mechanism of Action: Taxane that promotes
microtubule assembly preventing cell division
• Half-life: 4 days
• Primary clinical toxicity:
– Fatigue
– Diarrhea
– Weakness
• Primary lab effect: Anemia
• Monitoring of Treatment: CBC