Treatment of Cancer: Surgery, Chemo, & Radiation Flashcards
4 Phases of the Cell Cycle
G1
S
G2
M
G1: RNA and protein synthesis, cell growth, DNA repair
S: DNA completely replicated
G2: Additional RNA synthesis, protein & specialized DNA
M: Mitosis
Resting Phase
Growth Fraction
Resting Phase: Cells don’t engage in synthesis activities
Growth Fraction: Cell proportion of a tumor that are actively involved in division
Chemotherapy
MOA: Cell-cycle specific and nonspecific
Specific: Kills @ specific cycle phase
Nonspecific: Kills in all phases
-Alkylating agents, antitumor antibiotics, cisplatin
Alkylating Agent
One of 1st discovered
Directly damage DNA - work on all phases (nonspecific)
Blood cancer, HL, MM, sarcoma, lung/breast/ovary cancer
Class toxicities: N/V, myelosuppression, alopecia
May cause leukemia from long-term bone marrow damage
-risk is dose-dependent w/ highest risk 5-10 yrs out
Alkylating Agent Classes
Nitrogen Mustards: Cyclophosphamide, Ifosfamide
-Hemorrhagic cystitis from metabolic products - increase fluids
Platinum analogs: Carboplatin, Oxaliplatin, Cisplatin
- Nephrotoxic, neurotoxic, ototoxic
- Give w/ amifostine to prevent these
Antimetabolites
MOA: Interfere w/ DNA & RNA growth - substitute for normal aa
Damage occurs during S phase while chromosome is copied
Primary toxicities: Myelosuppression, N/V, mucositis, dermatologic
-rash, pruritus, injection site reaction
Antimetabolite Classes
Purine analogs - Mercaptopurine
Pyrimidine analogs - Fluorouracil, Gemcitabine
Folate Antagonists - Methotrexate (MTX, Trexal)
- SE: Toxicity effects rapid turnover cells (BM, mucosa)
- Get damage to liver and kidneys, decreased renal clearance
MTX - drugs that reduce excretion
ASA
NSAIDS
Amiodarone
Omeprazole
PCN
Phenytoin
Sulfa compounds
Drug given w/ MTX to reverse toxic effect
Drug given w/ Cisplatin to prevent toxic effects
Methotrexate - Leucovorin to reduce folic acid
-reverse toxic effects and prevent death
Cisplatin - IV Amifostine
Mitotic Inhibitors
AKA Anti-tumor antibiotics
MOA: Alter DNA - works in all phases of cell but mostly M
- Stops mitosis in M phase
- Inhibits enzymes and damages DNA in all phases
Mitotic Inhibitor Classes
Epothilones - Ixabepilone
Taxanes - Paclitaxel
Vinca Alkaloids - Vincristine
- Interfere w/ M phase
- SE: Neuropathy - distal to proximal; also get constipation (most common SE)
Anthracyclines - Daunorubicin, Doxorubicin
-SE: Cardiotoxicity causing systolic CHF - get MUGA scans
Topoisomerase Inhibitors
MOA: separate DNA strands so they can be copied during S phase
Topoisomerase I Inhibitors: Topotecan
Topoisomerase II Inhibitors: Etoposide (VP-16)
Increase risk of secondary cancers (AML) as early as 2-3 years after treatment
General Toxicities: Myelosuppression, alopecia, GI toxicity
Miscellaneous drugs
Mitomycin - C
Mitoxantrone (acts as topoisomerase II)
Actinomycin - D
Bleomycin
-SE: interphalangeal joint edema, hardened skin on palms and soles, anaphylactic/serum sickness-like reaction, pulmonary fibrosis
Get hypotensive reaction - severe/fatal after 1st dose in 1% patients
Targeted Chemo Therapies
Specifically attack cancer cell
Mutant genes or too many copies make them targets
Main treatment or to prevent recurrence
Imatinib (Gleevec)
Differentiating Agents
Cause cancer cells to mature into normal cells
Hormone Therapy
Sex hormones - slow growth of genital cancers by changing triggering hormone production
-Anti-estrogens (tamoxifen) - Commonly causes blood clots
Aromatase inhibitor (Anastrozole)
Progestin/Estrogen
Anti-androgens (Bicalutamide)
Gonadotropin-releasing hormone (GnRH) - Leuprolide
Immunotherapy
Active: Stimulates body’s own immune system to fight
Passive: Use immune system components created outside body
- Synthetic monoclonal Abs tag cancer cells for destruction
- “checkpoint inhibitors” which eliminate cancer cell immune override
Rituximab (Rituxan), BCG
Adjuvant
Neoadjuvant
Induction
Maintenance
Adjuvant: set course given to patients with no evidence dx after surgery or radiation
Neoadjuvant: Aim to eradicate micrometastatic dx or reduce inoperable dx
Induction: combo chemo given in high dose to cause remission
Maintenance: Long-term, low-dose regimen given in remission
-inhibits growth of remaining CA cells
Skin Toxicity
Erythema
Dry desquamation
Moist desquamation
Hyperpigmentation
Late: Hypopigmentation, Telangiectasis, fibrosis
Brain Radiation Toxicity
Acute: Fatigue, hair loss, skin erythema, desquamation
Late: Cognitive dysfunction, edema, necrosis
Head/Neck Radiation Toxicity
Acute: Mucositis, Taste dysfunction, Pain, Xerostomia
Late: Permanent Xerostomia, soft tissue fibrosis, osteoradionecrosis of mandible, dysphagia, pharyngeal stricture
Breast Radiation Toxicity
Acute - common and temporary
-Dry desquamation, fatigue, skin redness
Late - uncommon and permenant
-Fibrosis, cosmetic failure, hyperpigmentation
Lung Radiation Toxicity
Acute: skin reaction, fatigue, esophagitis (anesthetics/analgesics), cough, radiation pneumonitis
Late: Radiation pneumonitis, esophageal stricture, brachial plexopathy, pulmonary fibrosis
Esophageal Radiation Toxicity
Acute: Esophagitis, modest skin tan, fatigue, wt. loss, D/N/V
Late: esophageal stricutre/stenosis (60%), perforation, hepatobiliary
Abdominal Radiation Toxicity
Stomach, pancreas, hepatobiliary
Acute: Dyspepsia, anorexia, nausea, fatigue
Late: bowel obstruction, worsen DM secondary to pancreatic function, liver/kidney - possible renal failure/HTN
Pelvic Radiation Toxicity
Acute: Diarrhea, rectal irritation, urinary sx - nocturia, retention, fatigue
Late: Persistent urinary sx, bowel changes, erectile dysfunction
Anal Radiation Toxicity
Acute: Skin rxn, leukopenia, thrombocytopenia, proctitis, diarrhea, cysts
Late: Chronic diarrhea, rectal urgency, sterility, impotence, vaginal dryness/fibrosis, decreased testosterone
GYN Radiation Toxicity
Cystitis, proctitis, fistula, vaginal ulceration/stenosis/necrosis, skin rxn
Systemic Side effects of radiation
Fatigue is the only one
All other SE are limited to irradiated tissue
