Oncology / Chemotherapy

Oncology / Chemotherapy
NAPLEX Oncology / Chemotherapy PG 121

Characterized by uncontrolled cellular growth & proliferation
What is Cancer? Group of over 100 different diseases Characterized by uncontrolled cellular growth & proliferation Local tissue invasion Distant metastases As a group, the second-leading cause of death in Americans PG 121

Cancer Treatments PG 121 Surgery---local disease
Radiation---local or “regional” disease Alpha & beta particles, neutrons penetrate cell wall Chemotherapy- generally for metastatic disease or suspicion/high probability of micrometastatic dx can be used before surgery can cure some cancers (testicular & leukemias) Hormonal therapy- use in prostate, breast, uterine cancers; i.e. Prostrate – delay the progression of androgen-dependent cancer i.e. Breast – estrogen/progesterone receptor positive tumors Targeted therapy---most “mab”s (monoclonal antibodies) used alone or combination with chemo, targets a specific bioligic marker on the tumor or enzyme/compont See table 2-24 and 2-25 Target “Arrow” USE Route Side Effect HER2 Trastuzumamb (Herbeptin) Breast IV Cardiotoxicity CD33 Gemtuzumab (Mylotarg) AML Myleosuppression EGFR Cetuximab Colorectal Diarrhea CD52 Alemtuzumab CLL IV or SQ Myelosuppression PG 121

Angiogenesis Angiogensis – process of neovascularization – macrophages secrete angiogensis factor Occurs from existing capillaries Tumor cannot survive without adequate blood supply Tumors secretes vascular endothelial growth factor (VEGF) which acts on the endothelial growth factor receptor (EGFR) to “recruit” a blood supply MAB’s – target VEGF and EGFR Bevacizumab (VEGF) & Cetuximab (EGFR) target PG 122

Cell Cycle Specificity
M (mitosis) G1 phase (Gap 1) S phase (DNA synthesis) G2 (Gap 2) Phase-specific agents - Most active during a particular phase May be active during other phases Nonphase-specific agents - May favor a stage Dose dependent agents SEE TABLE 2-26 PG 122

Cell Cycle Specificity
M (mitosis) Vinca alkaloids taxanes G1 phase (Gap 1) S phase (DNA synthesis) Antimetabolites 5-FU, cytarabine, methotrexate G2 (Gap 2) Cell Cycle Specificity Alkylating Agents: Cisplatin Ifosfamide cyclophosphamide Hormones: Goserelin Tamoxifen Anastrozole Antibiotics: Bleomycin “rubicins” SEE TABLE 2-26 PG 122

Chemo Therapy Classes Antimetabolites - Interferes with synthesis of pyrimidine bases thus DNA synthesis Fluorouracil Folic Acid Analog – interferes with synthesis of pyrimidine bases thus DNA synthesis Methotrexate Purine Analogs – interferes with synthesis of purine bases Fludarabine Vinca Alkaloids – bind to tubulin to prevent formation of microtubules during mitosis Vincristine Podophyllotoxins – bind to tubulin – inhibiting topoisomerase II to cause DNA strand breaks Etoposide Taxanes – bind to tubulin – promotes synthesis of nonfunctional microtubules Paclitaxel Camptothecins – inhibits topiosomerase I, stabilizing single strand breaks in DNA Topotecan Antiandrogens – Inhibit uptake & binding of testosterone and didhydrotestosterone Flutamide (Eulexin) Progestins – suppresses release of luteinizing hormone and increase estrogen metabolism Megestrol (Megace) Antiestrogen – Bind to estrogen receptor in breast tissue – prevent binding of estrogen Tamoxifen (Nolvadex) Gonadotropin-releasing hormone analog – turn off negative-feedback release of FSH & LH, reduces testosterone and estrogen production Leuprolide (Lupron)

Common adverse events related to chemotherapy
Myelosuppression Neutropenia, anemia, thrombocytopenia Nausea/vomiting cisplatin Alopecia Cyclophosphamide Mucositis Peripheral neuropathy Renal dysfunction Rash Infusion reactions Flu-like syndrome MAB’s, docetaxel Hemorrhagic Cystitis cylcophosphamide PG 123

Common Adverse Effects Caused by Antineoplastic Drugs
** Information above is embedded in the tables p **

Which of the following medications for
cancer is associated with causing cardiotoxicity? a. tamoxifen (Nolvadex) b. fluorouracil (5-FU) c. paclitaxel (Taxol) d. doxorubicin (Doxil) e. methotrexate (Rheumatrex)

Drug for prevention of adverse events related to chemotherapy
Action Mesna (Mesnex) Inhibits hemorrhagic cystitis caused by ifosfamide Dexrazoxane (Zinecard) Reduces cardiotoxicity caused by doxorubicin Leucovorin (Wellcovorin) Reduced from of folic acid, dosed with MTX to preserve normal tissue, rescue dose based on MTX levels, also used with 5-FU Amifostine (Ethyol) Reduces renal toxicity caused by cisplatin PG 135 – Drug Antagonist Chart

Supportive Care – Nausea/Vomiting
5HT3 inhibitors – mod/high emetogenic regimens, give one dose prechemo and sometimes oral dose for 3 days postchemo Not for PRN use----can cause HA Ondansetron (zofran) – inhibits 1A2, 2C9, 2D6 (weak) Granisetron (Kytril) - less drug interactions Dolesetron (Anzement)- QTc prolongation - 2D6 (weak) Palonosetron (Aloxi) - subtrate 1A2, 2D6, 3A4 NK1 (neurokinin) inhibitor - highly emetogenic regimens only- Aprepitant (Emend) Drug interactions – 3A4 inhibitor and inducer Combination with 5HTs inhibitors Benzodiazepines – anticipatory N/V Lorazepem (Ativan) Dexamethasone – moderately emetogenic regimens or in combo with 5HT3 for delayed N/V PG

Supportive Care – N & V (continued)
Metoclopramide ADRs: sedation, explosive diarrhea, EPS Phenothiazines (prochloperazine [Compazine] promethazine [Phenergan]) Used PRN ADRs: drowsiness, dry mouth, akathesia, dystonia PG 124

Supportive Care Sargramostim (Leukine) Anemia
Hgb < 11 g/dL with symptoms; < 10 without symptoms EPO (Procrit) 40,000 units sq qweek Darbopoetin (Aranesp) 2.25 u/kg sq qweek Don’t forget Iron supplements Neutropenia Nadir occurs 1-2 weeks after chemo Absolute neutrophil count - ANC < 500 Filgrastim (Neupogen) 300 uq sq qd x 5-7 days Pegfilgrastim (Neulasta) 6 mg sq once 24 h post chemo Sargramostim (Leukine) 250 mcg SQ daily x 5-7 days PG 124

Which of the following is a therapeutic substitution for ondansetron?
a. Adaptin b. Kytril c. Inderal d. Seroquel e. Neurontin

All of the following exhibit antiemetic properties EXCEPT:
a. granisetron b. loratadine c. ondansetron d. prochlorperazine e. trimethobenzamide

NAPLEX Contraception PG 103

Contraception Mechanism of action: inhibit ovulation via negative feedback on the hypothalmus affecting FSH/LH release. Also alter genital tract, thicken cervical mucus. Hormonal Agents Estrogen - ethinyl estradiol, mestranol Progestin - desogestrel, norgestimate, levonorgestrel, norethindrone, norgesterel Types of oral contraceptive products---various doses but estrogen dose is held constant while progestin varies Monophasic - Desogen, Yasmin, etc. Biphasic - Ortho Novum 10/11, etc. Triphasic - Triphasil, tri-Norinyl, Cyclessa, etc. Progestin only - Micronor, Ovrette, Nor-qd Extended/continuous - Seasonale PG 103

Two Possible Components
Synthetic Estrogens Synthetic Progestins Estrogens – 2 Ethinyl Estradiol (EE) Mestranol Progestins – 12

Contraception (cont’d)
- Treatment should be delayed one year post menarche to allow for normal cycle development - Adverse effects of oral contraceptives Major: • Thromboembolism • Stroke • Myocardial infarction • Endometrial carcinoma • Pregnancy category X • Risk factors - Smoking - Age > 35 PG 103

Minor: • Weight gain, edema • Breakthrough bleeding - Early BTB: Insufficient estrogen activity; associated with amenorrhea - Late BTB: Insufficient progestin activity • Nausea and vomiting • Mild depression Drug Interactions: • Antimicrobials (griseofulvin, penicillins, tetracyclines) • Enzyme inducer (barbiturates, rifampin, PIs, St.Johns Wart.) PG 104

Drug Interactions with Oral Contraceptives
Anticonvulsants/Sedatives/Hypnotics: Induction of liver enzymes causes rapid metabolism of estrogen and increased binding of progestin and EE to SHBG - Sex hormone-binding globulin. Not a problem with valproic acid or some newer anticonvulsants such as lamotrigine. Antibiotics cause enterohepatic circulation disturbance. Rifampin increases the metabolism of progestins. I’m going to focus on antibiotics, because for any of the chronic medications on the list, it is best just to switch the patient to another form of birth control. Anticonvulsants/Sedatives/Hypnotics: Induction of liver enzymes causes rapid metabolism of estrogen and increased binding of progestin and EE to SHBG. Not a problem with valproic acid or some newer anticonvulsants such as lamotrigine. Antibiotics cause enterohepatic circulation disturbance. Rifampin increases the metabolism of progestins.

Non-Oral Hormonal Contraceptives
- Medroxyprogesterone acetate injection (Depo-Provera) – q 3 mths - Estradiol cypionate and medroxyprogesterone acetate (Lunelle) - DC - Intrauterine progesterone contraceptive system (Progestasert) - Levonorgestrel intrauterine system (Mirena) – can last up to 5 years - Ortho Evra patch – apply weekly for 3 weeks, 1 week off. Less effective if > 198 lbs Think about general counseling points about patches - Nuva Ring – intravaginal ring inserted for 3 weeks PG 104

Non-Hormonal Methods Contraception (cont’d)
Copper interuterine devide (ParaGard) – replaced every 10 years Spermicidal foams or suppositories – do not protect from sexual transmitted diseases. Barrier methods - condoms (latex, animal membrane, male versus female); cervical cap; diaphragms Natural family planning - basal body temperature method; symptothermal method; calendar (rhythm) method PG 104

Abortion Pill Mifepristone (Mifeprex-RU486)- generally used with misoprostol (Cytotec); for termination of early pregnancy (<49 days) - Increase for bacterial infections (sepsis), prolonged vaginal bleeding - Only be prescribe by physicians with a “Prescribers Agreement” - Not available in public pharmacies Emergency Contraceptive First dose within 72 hours of unprotected sex and a second dose 12 hours later - Levonorgestrel (high dose) (Plan B) - 89% effective Yuzpe Regimen Reduces risk of pregnancy by 75% Lo/Ovral 30ug EE + 0.3mg norgestrel 4 now and 4 in 12 hrs PG 104

Miscellaneous Hormonal Agents
Ovulation stimulants Estrogen antagonist Clomiphene citrate (Clomid, Serophene). Induces the release of FSH & LH – 6 cycles only Gonadotropins containing FSH (recombinant DNA technology) Follitropin alfa (Gonal-F) – FSH analogs Follitropin beta (Follistim) Urofollitropin (Fertinex) Human menopausal gonadotropins Menotropins (Pergonal, Humegon) – mixture of FSH/LH PG 105

Miscellaneous Hormonal Agents (cont’d)
Posterior pituitary hormones Vasopressin (Pitressin) - antidiuretic hormone for diabetes insipidus (injection) Lypressin (Diapid) - antidiuretic hormone for diabetes insipidus (intranasal) Desmopressin (DDAVP) - antidiuretic hormone, used to treat primary nocturnal enuresis and diabetes insipidus (nasal spray and tablets) – also useful for hemophilia A Oxytocin (Pitocin) - uterine stimulant – (injection) PG 105

Hormones (cont’d) Estrogens • Conjugated estrogen (premarin, etc.)
- synthetic forms : estradiol, estropipate • Estrogen dosage forms - tablet, cream, ring, transdermal patches, etc. - HRT improves lipid levels, reduces fracture risk, reduces vasomotor symptoms, DOES NOT reduce CV disease (WHI, HERS) - breast cancer risk - small, but there. Long-term use, family hx - Black Cohosh herbal has been touted for treatment of hot flashes, SSRIs, Soy product and clonidine are effective Selective estrogen receptor modulator (SERMs):raloxifene (Evista) - indicated for prevention and treatment of osteoporosis PG 106

When counseling a patient about medroxyprogesterone what are the important factors to discuss?
Weight gain Osteoporosis Risk of pulmonary embolism a. I only b. III only c. I and II only d. II and III only e. I, II, and III

Osteoporosis Low bone mass associated with age, hormone levels and medications. DEXA T-score >-1 is normal, -1 to -2.5 is osteopenia, and <2.5 is osteoporosis Oral calcium and vitamin D requirement Medications Oral Bisphosphonates ---1 st line Raloxifene Calcitonin Teriparitide Zoledronic acid (Reclast) I’m going to focus on antibiotics, because for any of the chronic medications on the list, it is best just to switch the patient to another form of birth control. Anticonvulsants/Sedatives/Hypnotics: Induction of liver enzymes causes rapid metabolism of estrogen and increased binding of progestin and EE to SHBG. Not a problem with valproic acid or some newer anticonvulsants such as lamotrigine. Antibiotics cause enterohepatic circulation disturbance. Rifampin increases the metabolism of progestins.

Paget’s disease is choatic bone resorption followed by choatic bone formation. Leads to enlarged but weakened and highly vasculized bone which is painful. PG

The medication Fosamax (alendronate):
I. must be taken with a meal II. is used to treat hot flashes III. is available as a once weekly dose a. I only b. III only c. I and II only d. II and III only e. I, II, and III

Drugs used in the prevention/treatment of osteoporosis include all of the following EXCEPT:
a. Evista b. Actonel c. Calcimar d. Prempro e. Proscar

Which of the following is an alternative treatment for osteoporosis in patients unable to tolerate oral biphosphonates due to GI upset? I. Zoledronic Acid II. Raloxifene III. Calcium + Vitamin D a. I only b. III only c. I and II only d. II and III only e. I, II, III

Which of the following products is a topical HRT?
a. Evamist b. Cenestin c. Premphase d. Provera e. FemHRT

NAPLEX Thyroid Case Study Page 106 PG 106

A goiter is caused by: a. hypothyroidism b. hyperthyroidism
c. deficient TSH d. a thyroid tumor e. a parathyroid dysfunction

L-thyroxine is the same as: a. T4
b. T3 c. liothyronine d. liotrix e. cytomel

Which of the following is used as an antithyroid drug: a. methamine
b. fluorouracil c. aspartame d. propylthiouracil e. protamine sulfate

Iodine-131 is a radioisotope that has a half-life of 8 days
Iodine-131 is a radioisotope that has a half-life of 8 days. How many days after a dose is administered will less than 1% of the original dose remain? a. 24 b. 32 c. 40 d. 56 e. 99

The parathyroid gland controls the body’s level of: a. iron
b. calcium c. iodine d. potassium e. glucose

Oncology / Chemotherapy

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