Anti-Neoplastic Therapy Flashcards
Cytotoxic Chemotherapy
- Traditional
- Toxic to all cells but more specific for rapidly dividing cells
- Alkylating agents
- Antimetabolites
- Natural products
- Miscellaneous agents
Alkylating Agents
- Cyclophosphamide, Ifosfamide
- Cisplatin, Carboplatin, Oxaliplatin
- Carmustine, Lomustine, Procarbazine
- Busulfan, Melphalan
- Chlorambucil
- Mechlorethamine
- Temozolomide/dacarbazine
- Mechlorethamine
- Streptozocin
- Thiotepa
Alkylating Agents: Toxicity
Common toxicities
- Nausea/Vomiting (most acute/some delay; often moderately to high emetogenic)
- Myelosuppression
- Alopecia
- Sterility/infertility
- Secondary malignacies
Cyclophosphamide/ifosfamide
- Hemorrhagic cystitis (primarily ifosfamide) due to acrolein metabolite
Cisplatin
- Nephrotoxicity
- Nausea/vomiting (acute and delayed)
- Ototoxicity
Oxaliplatin
- Neuropathies (exacerbated by cold temeratures)
Antimetabolites
- Structural analongs of naturally occurring substances necessary for specific biochemical reactions
Complete with normal metabolites OR
Falsely insert themselves for a metabolite normally incorporated into DNA and RNA - Most commonly active in the S phase
Antimetabolites Agents
Methotrexate Pemetrexed Pralatrexate Fludarabine Mercaptopurine Cladribine Pentostatin Clofarabine Capecitabine Fluorouracil Cytarabine Azacitidine Decitabine Gemcitabine Thioguanine Nelarabine
Antimetabolites: Toxicities
- Common toxicities: myelosuppression, mucositis, mild N/V, diarrhea
Methotrexate
- Renally toxicity
- Leucovorin rescue for high dose (>1gm/m2)
Cytarabine
- High dose therapy: Nervous system (cerebrllar) toxcitiy
- Ocular irritation - eye drops
Capecitabine
Hand-foot syndrome
Natural Products
- Antitumor antibiotics
- Plant alkaloids
Vinca alkaloids, taxanes, topoisomerase I & II - Marine-based products
- Enzymes
Antitumor Antibiotics
- Anthracyclines
- Mitomycin
- Dactinomycin
- Bleomycin
Anthracyclines
block DNA and RNA transcriptase
Mitomycin
Cross-links DNA
Dactinomycin
Blocks RNA synthesis
Bleomycin
Inhibits DNA synthesis (only cell-cycle specific agent)
Antitumor Antibiotics - Toxicities
- Nausea/Vomiting, Alopecia, Stomatitis, myelosuppression
- Bleomycin: lung toxicity - pulmonary fibrosis, Interstitial pneumonitis (lifetime max 400 units)
- Anthracyclines: cardiotoxicity - congestive heart failure
Myocardiotoxicity
(dose-dependent)
- Production of toxic free radicals, membrane lipid peroxidation leading to irreversible damage and replacement by fibrous tissue
- Risk factors: Cumulative dose, patient age, concomitant chemotherapy with known cardiotoxicity, radiation therapy
- Early toxicity: HF can develop within 3 months following completion
- Late toxicity: Symptoms may appear one decade following
completion
- Dexrazoxane MOA: EDTA-like chelating agent, binds intracellular iron released following lipid peroxi
Microtubule agents
- synthetic and semi-synthetic
- different mechanisms of action
- Taxanes (docetaxel, paclitaxel, cabazitaxel, nab-paclitaxel)
- Vinca alkaloids (vinblastine, vincristine, vinorelbine)
Microtubule Toxicities
- Taxanes
Docetaxel – neuropathies, peripheral edema,
hypersensitivity reactions
Paclitaxel – neuropathies, hypersensitivity reactions
Premedicate with H1 and H2 blocker + steroid - Vincristine
neuropathies, constipation, DO NOT give intrathecally
Topoisomerase I inhibitor
irinotecan, topotecan
Topoisomerase II inhibitor
etoposide, teniposide
enzyme
asparaginase, pegaspargase
Topoisomerase I inhibitor Toxicities
Diarrhea (2 phase)
- immediate - cholinergic reaction
- delayed - loperamide, diphenoxylate/atropine
Topoisomerase II inhibitor Toxicities
secondary cancer
Enzyme Toxicities
hypersensitivity reaction, hyperglycemia, pancreatitis, coagulopathies
- E. coli derived PEGylated erwinia-derived
Marine-based products
Eribulin - sea sponge
- microtubule-like agent
- toxicities: fatigue, peripheral neuropathy, Chemo Induced N/V (CINV)
Trabectedin - sea squirt
- mechanism - somewhat like an alkylating agent
- toxicities: fatigue, hand-foot syndrome, CINV, hepatic damage
Hormonal Treatment
- Block production of hormones or hormone receptors in the body
- Anti-estrogens
- Anti-adrogens
- Luteinizing hormone-releasing hormone (LHRH) analogs
- Ex. Breast, prostate cancer
Serm Hormone Therapy
- Tamoxifen
- Use in hormone receptor + dosease: premenopausal, postmenopausal
- Benefits: decrease odds of recurrence, increase 15 year survival
- ADE: cataracts, endometrial cancer, VTE CYP2D6 active metabolite
Aromatase Inhibitor Horomone Therapy
- Letrozole, anastrozole, exemestane
- Use in hormone receptor + dosease: postmenapausal (preferred), premenopausal when in comboination with ovarian suppression
- Postmenopausal: decrease in recurrence
- Premenopausal:
- ADE: osteoprosis, fractures, arthralgias
LHRH Agonists
- Inhibit the pituitary (through negative feedback) from releasig LH and FSH which stops stimulation of the testes to produce testosterone (can also be used in breast cancer with same MOA but stops stimulation of ovaries to produce estrogen
- Tumor flare
- Leuprolide, goserelin, triptorelin
LHRH Antagonists
- directly inhibits pituitary from releasing LH and FSH
- Degarelix
Antiandrogens
- Blocks androgen receptor
- Bicalutamide, Flutamide, Nilutamide, Enzalutamide
- Abiraterone
Targeted Agents
- Identifies certain features of a cancer cell that make it different from the normal cell
- prevent tumor cells from entering cell cycle or target signals that trigger cancer growth, metastasis, and immortality
Molecularly targeted therapies
Block signaling inside the cell
Monoclonal Antibodies
Antibodies that match an antigen on the cancer cell surface
VEGF signaling Pathway (VSP) Inhibitors
- Vascular endothelial growth factor
- Hypertension proteinuria, bleeding, impared wound healing
- Hypertension may indicate effectiveness
- Becacizumb, Sunitinib, Pazopanib, Regorafenib
EGFR Inhibitors
- epidermal growth factor receptor
- Acneiform rash
- Rash may indicate effectiveness
- Erlotinib, gefitinib, alectinib, cetuximab, panitumumab
EGFR - Acneiform Rash
acneiform-like rash with EGFR inhibitors
- tetracyclines
- topical antibiotics
- surrogate marker for response?
mTOR inhibitors
mammalian target of rapamycin
- hyperglycemia, dyslipidemia, mucosal sensitivity, ulcers
- DDI 3A4
- Everolimus, Sirolimus, temsirolimus
BCR-ABL Mutation inhibitor
Imatinib: edema, n/v Dasstinib: neutropenia, edema, n/v Nilotinib: n/v, fatigue Ponatinib: cardiac Bosutinib: diarrhea, n/v - CYP3A4 substrate (except ponatinib) DDI possible - Imatinib 3A4 inhibitor
mTOR inhibitor Toxicities
mucosal ulcer
CD20
rituximab, ofatumumab, obinutuzumab
HER2 inhibition
human epidermal growth factor receptor-2
- Trastuzumb, pertuzumab, Lapatinib
Trastuzumb, pertuzumab Toxicities
cardiotoxicity
Lapatinib
N/V, fatigue, diarrhea, hand-foot syndrome; drug interactions with strong 3A4 inducers/inhibitors
CD20 Toxicities
infusion reactions, myelosuppression
Monoclonal antibodies Toxicities
Potential hypersensitivity reactions based on mAb origin
• QT prolongation
Nilotinib, pazopanib, ponatinib
Brentuximab
Neuropathy
Vemurafenib
Colitis
Bortezomib
Neuropathies
Target Agents Toxicities General
- Fatigue, Hair thinning
- Low grade (if at all)
n/v, myelosuppression - Hair depigmentation
- Dysphonia
- Hypothyroidism (sunitinib, pazopanib, regorafenib)
Immunological Therapies
Interferon Interleukin Lenalidomide Thalidomide CTLA-4 inhibitors PD-1/PD-L1 inhibitors Cancer vaccine
PD1 and PD-L1 inhibitors
Pembrolizumab
Nivolumab
Pembrolizumab
- Melanoma, gastric, head & neck, Hodgkin lymphoma, lung cancer, urothelial, Merkel cell
- Toxicities: fatigue, itching, rash
Nivolumab
- Melanoma, lung cancer, colorectal cancer, head & neck, hepatocellular, Hodgkin lymphoma, renal cell cancer, urothelial cancer
- Toxicities: fatigue, malaise
Anti-PD-L1
Atezolizumb
Avelumab
Durvalumab
Bone Marrow Transplants
Autologous (self) - high dose with stem cell rescue
allogeneic (other)
Nonmyeloablative
Stem Cell Sources
Bone marrow
Peripheral blood
Cord Blood
