Exam III Oncology Flashcards
Cancer Cell Characteristics
Uncontrolled cellular growth
Ability to invade adjacent structures and/or travel to distant areas
Incapable of physiologic functions of the mature tissue of origin
Altered proteins, enzyme systems, membrane characteristics, and cytogenetics
Cancer treatment types
Radiation
Surgery
Chemotherapy
Anti-Cancer Therapy
Cytotoxic therapies
Anti-hormonal therapies
Targeted therapies
Immunotherapy
Blood and marrow transplant (BMT)
Tumor Staging and treatment terminology
TNM Staging (Tumor, Nodal status, Metastasis) for Solid Tumors (Stage I, II, III, IV)
Adjuvant chemotherapy:
-Given after surgery to reduce risk of local and systemic recurrence
Neoadjuvant chemotherapy:
-Given prior to surgical intervention to reduce tumor size or to remove micrometastases
Oncogene
Tumor suppressor gene
Anticancer Drugs
Alkylating agents
-Cyclophosphamide, Cisplatin
Protease Inhibitor
-Bortezomib, Carfilzomib
Antimetabolites
-5-Fluorouracil, Methotrexate, Gemcitabine, 6-Mercaptopurine
Natural Products
-Etoposide, Paclitaxel, Vincristine
Antitumor antibiotics
-Bleomycin, Doxorubicin, Mitomycin
Hormonal
-Prednisone, Tamoxifen
Misc
-Imatinib, Cetuximab
Cytotoxic Chemotherapy
Traditional
Toxic to all cells, but more specific for rapidly dividing cells
Tumor Growth Kinetics
Doubling time
-Time needed for a tumor cell population to double in size
Gomperzian growth
-Early growth is exponential, but as tumor gets bigger, growth slows due to decreased nutrients/blood supply
Log-kill hypothesis
A given dose of chemotherapy kills the same fraction of tumor cells regardless of the size of the tumor at the time of treatment
Principles of Cytotoxic Chemotherapy - Combination chemotherapy or “Regimen”
Good single-agent activity against tumor
Different mechanism of action
Different toxicities or different onset of toxicities
Maximum cell kill within toxicity limits
Different mechanisms of action to target a cancer
Decrease drug resistance
Principles of Cytotoxic Chemotherapy - Dosing / Admin
Dosing
-Dose usually based on body surface area (BSA)
–Also mg/kg dosing or flat dosing
-Which weight to use
–Ideal, actual, adjusted
Administration
- Cycles every 14, 21, or 28 days most common
- Dose intensity and dose density
Alkylating agents - MoA
Prevents cell division by cross-linking DNA strands and decreasing DNA synthesis
Cell cycle non-specific
Myelosuppression is generally the dose-limiting toxicity
Alkylating Agents
Cyclophosphamide, Ifosfamide
Cisplatin, Oxaliplatin
Carboplatin,
Carmustine, Lomustine
Busulfan, Melphalan
Chlorambucil
Mechlorethamine
Temozolomide/Dacarbazine
Mechlorethamine
Streptozocin
Thiotepa
Alkylating agents: Common Toxicity
Nausea/Vomiting
- Mostly acute - some delay
- Often moderately to highly emetogenic
Myelosuppression
Alopecia
Sterility/Infertility
Secondary Malignancies
Alkylating Agents: Specific Toxicities
Cyclophosphamide/Ifosfamide
-Hemorrhagic cystitis (primarily Ifosfamide) due to acrolein metabolite
–Mesna
Cisplatin
- Nephrotoxicity
- N/V (acute and delayed)
- Ototoxicity
Oxaliplatin
-Neuropathies (exacerbated by cold temperatures)
Antimetabolites
Structural analogues of naturally occurring substances necessary for specific biochemical reactions
- Compete with normal metabolites or
- Falsely insert themselves for a metabolite normally incorporated into DNA and RNA
Most commonly active in the S phase
DNA and RNA Bases
Purine Bases: A and G
Pyrimidine bases: T (DNA), U (RNA), and C
De-Novo base synthesis or salvaged bases used in building DNA and RNA
Continuously dividing cells favor using de novo synthetic pathway
Antimetabolites Most Important
Capecitabine
Cytarabine
Fluorouracil
Methotrexate
Antimetabolites Rest
Azacitidine
Cladribine
Clofarabine
Decitabine
Fludarabine
Gemcitabine
Methotrexate
Mercaptopurine
Nelarabine
Pentostatin
Pemetrexed
Pralatrexate
Thioguanine
Metabolites that use DHFR
Methotrexate
Flourouracil
Antimetabolites: Toxicities
Common toxicities: myelosuppression, mucositis, mild N/V/D
Methotrexate (MTX)
Renal toxicity
Leucovorin rescue for high dose (>1 gm/m2)
Cytarabine
High dose therapy: nervous system (cerebellar) toxicity
Ocular irritation - eye drops
Fluorouracil (leucovorin)
Capecitabine: Hand-foot syndrome
Natural Products
Antitumor antibiotics
Plant alkaloids
Vinca alkaloids
Taxanes
Topoisomerase I & II
Marine-based products
Enzymes
Antitumor Antibiotics
Anthracyclines - block DNA and RNA transcription
Daunorubicin - Lifetime dose Limit
Doxorubicin - Lifetime dose limit
Epirubicin
Idarubicin
Mitoxantrone
Mitomycin - cross-links DNA
Dactinomycin - blocks RNA synthesis
Bleomycin - inhibits DNA synthesis (only cell-cycle specific agent)
Doxorubicin – Streptomyces peucetius
Bleomycin – Streptomyces certicillus
Mitomycin – Streptomyces caespitosus
Dactinomycin – Streptomyces parvulus
Antitumor Antibiotics - Toxicities
N/V, alopecia, stomatitis, myelosuppression
Bleomycin: lung toxicity - pulmonary fibrosis, interstitial pneumonitis
Lifetime max 400 units
Anthracyclines: cardiotoxicity - CHF
Lifetime max dose (doxorubicin 450 mg/m2 or equivalent)
Dose-Dependent Cardiotoxicity of Anthracyclines
Antitumor Antibiotics - Myocardiotoxicity
Myocardiotoxicity (dose-dependent):
Production of toxic free radicals, membrane lipid peroxidation leading to irreversible damage and replacement by fibrous tissue
Risk Factors: Cumulative dose, PT 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 releaeed following lipid peroxidation
Natural Products - Microtubule agents
M-Phase
Synthetic and semi-synthetic
Diffuse mechanisms of action
Vinca alkaloids prevent microtubule assembly
Taxanes prevent microtubule disassembly
Plant Alkaloids: Microtubule Toxicities
Taxanes
Docetaxel - neuropathies, peripheral edema, hypersensitivity reactions
Paclitaxel - neuropathies, hypersensitivity reactions
-Premedicate with H1 and H2 blocker + steroid
Vinca Alkaloids
Vincristine - neuropathies, constipation, DO NOT give intrathecally
Vinblastine
Vinorelbine - myelosuppression
Natural Products and Toxicities
Topoisomerase I inhibitors
Irinotecan, Topotecan
Topoisomerase II inhibitors
Etoposide, Teniposide
Enzyme
Asparaginase, Pegaspargase
Irinotecan - diarrhea (2 phases)
Immediate - cholinergic reaction
Delayed - Ioperamide, Diphenoxylate/Atropine
Etoposide - secondary cancers
Asparaginase - hypersensitivity reaction, hyperglycemia, pancreatitis, coagulopathies
E Coli-drevived PEGylated, Erwinia-derived
Natural Products-Marine-based products
Eribulin - Sea sponge
Microtubule-like Agents
Toxicities: Fatigue, peripheral neuropathy, CINV
Trabectedin - Sea squirt
Mechanism - somewhat like an alkylating agent
Toxicities: fatigue, hand-foot syndrome, CINV, hepatic damage
Hormonal Treatment
Blocks production of hormones or hormone receptors in the body
Anti-estrogens
Anti-androgens
Luteinizing hormone-releasing hormone (LHRH) analogs
Ex: breast, prostate cancer
Hormone Therapy Chart
Hormonal Therapy: Prostate Cancer
LHRH agonists
Inhibit the pituitary (through negative feedback) from releasing 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 receptors
Bicalutamide, Flutamide, Nilutamide, Enzalutamide, Apalutamide
Abiraterone
HPT Axis
Targeted Agents
Identifies certain features of a cancer cell that make it different from the normal cell
Prevents Tumor cells from entering cell cycle or target signals that trigger cancer growth, metastasis, and immortality
Monoclonal antibodies
Antibodies that match an antigen on the cancer cell surface
Molecularly targeted therapies
Block signalling inside the cell
Targeted Agents names/types
Targets of targeted agents
VEGF signalling pathway (VSP) inhibitors
(VEGF(R) inhibitors - vascular endothelial growth factor (receptor))
HTN, proteinuria, bleeding, impaired wound healing
HTN may indicate effectiveness
Bevacizumab, Sunitinib, Pazopanib, Regorafenib, ETC.
EGFR inhibitors - epidermal growth factor receptor
Acneiform rash
Rash may indicate effectiveness
Erlotinib, Gefitinib, Alectinib, Cetuximab, Panitumumab
EGFR Acneform RAsh
Targets PT-II
mTOR inhibitors - mammalian Target of Rapamycin
Hyperglycemia, dyslipidemia, mucosal sensitivity, ulcers
Drug interactions - 3A4
Everolimus, sirolimus, temsirolimus
BCR-ABL mutation inhibition -
Imatinib (edema, N/V), Dasatinib (neutropenia, edema, N/V), Nilotinib (N/V, fatigue), Ponatinib (cardiac), Bosutinib (N/V/D)
CYP3A4 substrates (except ponatinib) so drug interactions possible
Imantinib also a 3A4 inhibitor
mTOR inhibitor Toxicities
Specific Targets
CD20 - Rituximab, Ofatumumab, Obinutuzumab - (infusion RXN, myelosuppression)
HER2 inhibition - human epidermal growth factor receptor - 2
Trastuzumab, Pertuzumab - Cardiotoxicity
Lapatinib - N/V/D, fatigue, hand-foot syndrome; drug interactions with strong 3A$ inducers/inhibitors (also cardiotoxicity as it is a HER2 INH)
Targeted Agents: Toxicities (MABS)
MAB: Brentuximab (neuropathy), Vemurafenib (Colitis), Bortezomab (Neuropathies)
Potential hypersensitivity reactions based on mAB origin
QT prolongation
Nilotinib, Pazopanib, Ponatinib
Fatigue, hair thinning
Low grade (if at all)
N/V
Myelosuppression
Targeted Agent Toxicities
Hair depigmentation (and repigmentation)
Dysphonia
Hypothyroidism
Sunitinib, Pazopanib, Regorafenib
Immunological Therapies
INF
Interleukin
Lenalidomide
Thalidomide
CTLA-4 inhibitors
PD-1 inhibitors
Cancer Vaccine
PD-1 and PD-L1 Inhibitor
Pembrolizumab
??
Big adverse effects
LO
