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Learn about the common urologic agents used in the treatment of GU cancers, their mechanisms of action, clinical toxicities, and primary lab effects. Monitoring of treatment is also discussed.
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Common Urologic Agents Used in the GU Cancer Patient Jay Simhan, MDMarch 2012
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
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
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
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