Oncology

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CHAPTER 17 Oncology

II. Risk factors

A. Environmental

B. Occupational

2. Benzene, chromium, nickel

III. Principles of tumor growth

A. Tumor growth is exponential.

B. Chemotherapy kills a certain percentage of cells, not a particular number.

1. Spread of cancer cells from tumor site to distant sites

a. Spread by blood and lymphatic pathways

VI. Diagnosis and staging

A. Diagnosis: pathologic evaluation and biopsy

B. Staging: determines prognosis, metastasis, and treatment

C. TNM classification (T = tumor, N = node, M = metastasis)

VII. Types of cancer

A. Carcinoma: cancer that begins in the skin or in tissues that line or cover internal organs

B. Sarcoma: cancer of the bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue

C. Leukemia: cancer that starts in blood-forming tissue such as bone marrow and causes production of large numbers of blood cells to be produced and enter the bloodstream

D. Lymphoma: cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course.

E. Adenoma: a noncancerous tumor that starts in gland-like cells of the epithelial tissue (thin layer of tissue that covers organs, glands, and other structures within the body)

VIII. Cancer treatment

C. Chemotherapy

D. Immunotherapy

E. Hormone therapy

IX. Chemotherapy

A. Purpose: destroy cells that may have spread from primary site

1. Curative: entirely free of disease

2. Adjuvant: keep it from spreading

3. Neoadjuvant: reduce tumor burden or spare organ

4. Palliative: relieve symptoms (i.e., pain) and allow individual to live comfortably

C. Common routes of chemotherapy administration

2. Intravenous (IV)

4. Intracavitary

5. Intra-arterial

D. Classification of chemotherapeutic agents

a. Anthracycline antibiotics

(1) Examples: daunorubicin, liposomal daunorubicin doxorubicin, epirubicin, idarubicin, valrubicin

b. Miscellaneous

(1) Examples: bleomycin, mitomycin, plicamycin, dactinomycin

6. Tyrosine kinase inhibitors

(a) Examples: imatinib, gefitinib

7. Miscellaneous

(1) Examples: L-asparaginase, hydroxyurea, estramustine, bexarotene, arsenic trioxide, denileukin diftitox, bortezomib

E. Adverse effects of chemotherapy

2. Extravasation

a. Leakage of drug into surrounding tissues

b. For doxorubicin, daunorubicin, may apply cold pack

c. For vincristine, vinblastine, vinorelbine, taxanes, mechlorethamine, apply warm pack (avoid cold application)

3. Bone marrow suppression: Common dose-related toxicity

4. Cardiotoxicity

a. Doxorubicin, daunorubicin, cyclophosphamide

b. Patients should be monitored; early detection is key.

c. Dexrazoxane, a cardioprotectant (Totect, Zinecard); also used for treatment of extravasation

5. Nephrotoxicity

a. Cisplatin, carboplatin, carmustine

2. Diuresis with mannitol and/or furosemide

3. Amifostine (Ethyol) may be given before cisplatin but may cause hypotension

6. Hemorrhagic cystitis

a. Cyclophosphamide, ifosfamide

b. Treatment: mesna reduces the incidence of hemorrhagic cystitis

7. Hepatotoxicity

a. L-asparaginase, nitriturias, methotrexate, 6-mercaptopurine, and others

8. Neurotoxicity

a. CNS (headache, somnolence, confusion): cytarabine (cerebellar toxicity), asparaginase, ifosfamide, fluorouracil, vincristine, vinblastine

b. Peripheral neuropathy: vincristine, cisplatin, paclitaxel, fludarabine, docetaxel

9. Pulmonary toxicity

a. Bleomycin (pulmonary fibrosis, infiltrates, cough), busulfan

(1) Interstitial pneumonitis: carmustine, chlorambucil, cyclophosphamide, mitomycin, methotrexate, fludarabine, melphalan, cytarabine

a. Cyclophosphamide, ifosfamide, fluorouracil, dactinomycin, doxorubicin, daunorubicin, bleomycin, paclitaxel, docetaxel

13. Sterility/infertility

a. Alkylating agents, procarbazine, methotrexate, fluorouracil, busulfan, cyclophosphamide

14. Ocular toxicity

a. Cytarabine (conjunctivitis), busulfan (cataracts), vinca alkaloids (optic neuritis), cisplatin (optic neuritis)

F. Radiation therapy

1. Uses high-energy rays to kill cancer cells

2. Local therapy

3. Used alone or in conjunction with chemotherapy

1) Depends on the stage of the disease and the overall health of the patient

2) Used in conjunction with chemotherapy and radiation therapy

Chemotherapeutic Agent (generic name)	Brand	Indications
ALKYLATING AGENTS
Nitrogen mustards Chlorambucil Cyclophosphamide Ifosfamide Mechlorethamine Melphalan

Cytoxan, Neosar

Chronic lymphocytic leukemia

Hodgkin and non-Hodgkin lymphoma

Waldenström macroglobulinemia

Breast (palliative)

Chronic lymphocytic leukemia

Recurrent testicular cancer and germ cell tumors

Hodgkin and non-Hodgkin lymphoma

Nonsmall cell lung cancer (NSCLC)

Lung (palliative)

Cutaneous T-cell lymphoma

Thiotepa Thioplex Chronic myelogenous leukemia (CML) Busulfan

CML (palliative)

Brain neoplasms (malignant glioma)

Mutliple myeloma

Hodgkin’s and non-Hodgkin’s lymphoma

Dacarbazine DTIC-Dome

Hodgkin lymphoma

Soft tissue sarcomas

Procarbazine Matulane

Hodgkin lymphoma

Platinum compounds

Platinol

ANTIMETABOLITES Fluorouracil, 5-FU Adrucil Prolong survival (combination with leucovorin) Floxuridine FUDR

Methotrexate Methotrexate Osteosarcoma Leucovorin Wellcovorin, Leucovorin Colorectal (palliative; combination with 5-FU) Hydroxyurea

Ovarian (refractory)

Essential thrombocytosis and polycythemia vera

Thioguanine, 6-TG Thioguanine Tabloid

Acute lymphocytic leukemia (ALL)

Mercaptopurine, 6-MP Purinethol ALL Cytarabine DepoCyt Lymphomatous meningitis (intrathecal) Pentostatin Nipent Hairy cell leukemia Fludarabine Fludara B-cell lymphocytic leukemia (CLL) Cladribine Leustatin, 2-CdA Active hairy cell leukemia Asparaginase Elspar ALL (combination) Gemcitabine (Gemzar) NSCLC (advanced (Stage IIIA or IIIB) or metastatic (Stage IV)) ANTIBIOTIC AGENTS

Doxorubicin liposomal

Adriamycin, Rubex

Breast (adjunct)

AIDS-related Kaposi sarcoma

Epirubicin Ellence Breast

daunorubicin liposomal

daunorubicin, daunomycin

Advanced, HIV-related Kaposi sarcoma

Idarubicin Idamycin

Acute myeloid leukemia (AML)

Acute nonlymphocytic leukemia (ANLL)

Mitoxantrone Novantrone

Prostate (advance refractory, combination therapy)

Dactinomycin Cosmegen

Soft tissue sarcoma

Rhabdomyosarcoma

Germ cell tumors

Gestational trophoblastic disease

Choriocarcinoma

Sarcoma botryoides

Bleomyicn Blenoxane Malignant pleural effusion (MPE), prevention of recurrent pleural effusions BIOLOGIC AGENTS

Interleukin-11, oprelvekin

Supportive treatment (stimulate bone marrow to produce platelets; decrease the need for platelet transfusions)

interferon alpha 2a

interferon alpha 2b

Hairy cell leukemia

AIDS-related Kaposi sarcoma (interferon alpha 2b)

Malignant melanoma (interferon alpha 2b)

Non-Hodgkin lymphoma (interferon alpha 2b)

BCG

Immunization against tuberculosis (TB)

Levamisole Ergamisol Colon cancer (combination with 5-FU) Sargramostim, GM-CSF Leukine Accelerate WBC recovery (used in AML, non-Hodgkin lymphoma, acute lymphocytic leukemia, or Hodgkin disease) Octreotide Sandostatin Control certain symptoms (e.g., diarrhea, flushing)

Tretinoin, ATRA

AIDS-related Kaposi sarcoma

Acute promyelocytic leukemia (APL)

HORMONAL AGENTS Tamoxifen Nolvadex Breast Megestrol acetate Megace

Supportive treatment for severe loss of appetite

Anastrozole Arimidex Breast (adjunct) Letrozole Femara Breast Goserelin

Zoladex Implant

Breast Leuprolide Eligard Prostate Bicalutamide Casodex Prostate Flutamide Eulexin Prostate PLANT-DERIVED AGENTS Vincristine Oncovin

Hodgkin and non-Hodgkin lymphoma

Rhabdomyosarcoma

Multiple myeloma

Chronic leukemias

Vinblastine Velban

Hodgkin and non-Hodgkin lymphoma

Mycosis fungoides (T-cell lymphoma)

Choriocarcinoma

Vinorelbine Navelbine NSCLC Etoposide

Small cell lung cancer (SCLC)

Teniposide Vumon ALL Paclitaxel

AIDS-related Kaposi sarcoma

Docetaxel Taxotere

Topotecan Hycamtin

Irinotecan Camptosar

MISCELLANEOUS

Monoclonal antibodies

Non-Hodgkin lymphoma

Tyrosine Kinase Inhibitor

Gleevec

Gastrointestinal

EGFR Inhibitors

VEGF inhibitors

Avastin Reversible posterior leukoencephalopathy syndrome (NSCLC)

Depiro J. Pharmacotherapy: A pathophysiological approach, ed 7. McGraw-Hill Medical, 2008.

United States National Institutes of Health, National Cancer Institute (NCI). General website for information and links to information regarding cancer and cancer treatment. Available at http://www.cancer.gov

http://www.nlm.nih.gov http://www.nlm.nih.gov/medlineplus/ency/article/003645.htm Accessed November 16, 2009

http://www.uspharmacist.com http://www.uspharmacist.com/content/t/oncology/c/10350/ Accessed November 16, 2009

http://www.chemocare.com http://www.chemocare.com/managing/nephrotoxicity-renal-toxicity.asp

PATIENT PROFILE

Patient Initials: DB

Height: 5′ 9″

Allergies: No known drug allergies (NKDA)

Current: Three months ago, the patient reported significant urinary flow symptoms to physician. At that time, the patient had an elevated PSA and a noted mass with digital rectal exam. The mass was confirmed with an ultrasound procedure, and a biopsy revealed that DB had prostate cancer. There is no metastatic disease at this time.

Medical History:

None significant to current issues. No chronic health problems except mild osteoarthritis of the knees and hands.

Social History:

Tobacco use: None in the past 40 years; smoked in young adulthood but less than 1 pack per day

Alcohol use: Rare

Current Medications:

None, occasional use of nonprescription Aleve for osteoarthritis

PATIENT PROFILE QUESTIONS

1. Part of DB’s treatment regimen will include the use of a luteinizing hormone–releasing hormone (LHRH) agonist to significantly reduce androgen levels. Which of the following is an LHRH agonist?

d. Saw palmetto

Answer: b. Goserelin is the LHRH agonist. Finasteride is an antiandrogen (5-alpha reductase inhibitor) that reduces conversion of testosterone to dihydrotestosterone (DHT). Tamsulosin is a selective alpha receptor antagonist. Saw palmetto is a natural dietary supplement used for prostate health.

REVIEW QUESTIONS

(Answers and Rationales on page 364.)

1. Which of the following drugs is NOT a part of the chemotherapy regimen–MOPP?

a. Mechlorethamine

c. Procarbazine

2. Which of the following agents CANNOT be injected intrathecally?

d. Methotrexate

e. Hydrocortisone

3. Which of the following is NOT an alkylating agent?

b. Mechlorethamine

4. Which of the following is NOT a side effect of tamoxifen?

e. Peripheral edema

5. Which of the following is a proposed mechanism of doxorubicin?

A. Intercalation

b. Inhibit protein synthesis

c. Iron chelation

d. All of the above

e. None of the above

7. Depolymerization of microtubules is the mechanism of action of:

c. Methotrexate

8. Which of the following is true of irinotecan?

a. It may cause diarrhea

b. It may cause hypovolemia

c. It may be used to treat colon cancer

d. It is a topoisomerase II inhibitor

9. All of the following are true about nilutamide (Nilandron) EXCEPT:

a. It is an antiandrogen

b. It is used for prostate cancer

c. It is not available for oral use

d. May elevate liver enzymes

e. Patients using nilutamide should wear tinted glasses

10. 5-Fluorouracil:

a. Is used to treat colorectal carcinoma

b. Can be administered orally

c. May cause constipation

d. Activates thymidylate synthetase

e. Has a duration of action of 2-3 days

12. Doxorubicin may cause all of the following EXCEPT:

a. Nephrotoxicity

b. Myelosuppresion

c. Cardiac disease

d. Gastrointestinal toxicity

e. It may cause any of the above

13. Allopurinol and mercaptopurine, when combined, produce severe side effects. This is caused by:

a. Quanylate kinase inhibition

b. Xanthine oxidase inhibition

c. Accumulation of allopurinol

d. Accumulation of chemotherapeutic agent

14. Which of the following is an alkylating agent:

c. Cyclophosphamide

15. Which of the following may cause hemorrhagic cystitis?

a. Cyclophosphamide

c. Methotrexate

e. None of the above

17. Cyclosporine:

a. Causes severe myelosuppression

b. Causes hepatotoxicity

c. Does not elevate serum creatinine

d. Is useful in the treatment of many solid tumors

18. What is the most common use of cyclosporine?

c. Immunosuppression

19. What side effect is associated with cisplatin?

a. Nephrotoxicity

c. Electorlyte imbalance

20. Why are most cancers treated with a combination of chemotherapeutic agents?

a. Different mechanisms of action

b. Different toxicity profiles

c. Different mechanisms of tumor resistanc

21. Which of the following may cause congestive heart failure?

b. L-Asparaginase

d. Cyclophosphamide

22. Which of the following is a side effect of 17-alpha alkylated androgens?

a. Hepatic adenocarcinoma

b. Peliosis hepatitis

c. Elevated hepatic transaminases

d. Cholestatic hepatitis

e. All of the above

23. Which of the following is an appropriate use of androgens?

a. Breast carcinoma

b. Hereditary angioneurotic edema

c. Hypogonadism

d. Erythropoiesis

e. All of the above

25. Which of the following is an appropriate indication for anti-androgens?

a. Prostate cancer

b. Male pattern baldness

e. All of the above

26. Which of the following is INCORRECT?

a. Aminoglutethimide inhibits the rate-limiting step in cortisol synthesis

b. Trilostane decreased aldosterone synthesis

c. Metyrapone inhibits 11-hydroxylase

d. Ketoconazole inhibits cortisol synthesis

e. Aminoglutethimide inhibits androstenedione conversion to testosterone

27. Interferons:

a. Enhance MHC class I and II expression

b. Have antioncogenic effects

c. Are produced in response to viral infections

28. Interleukin 1:

a. Enhances endothelial adhesion factor expression

b. Are analgesic

c. Act to reset the hypothalamic thermoregulatory center

29. Which of the following is true regarding interleukins (IL)?

a. IL-2 is produced by B-lymphocytes

b. IL-4 causes IgG and IgE synthesis and B cell proliferation

c. IL-6 is immunosuppressive

d. IL-7 is produced by Th2 cells

e. Il-10 activates Th1 cytokine production

31. Which of the following is true regarding lymphocytes?

a. NK cells causes lysis of tumor cells

b. Helper T cells cause lysis of virally infected cells

c. B cells cause lysis of virally infected cells

d. Cytotoxic T cells release cytokines that promote B cell activation

e. B cells account for 80% of all lymphocytes

32. Which of the following is FALSE concerning the complement pathway?

a. The classical pathway is initiated by the C1 complex

b. Decay accelerating factor can inhibit C3 convertase

c. C3a and C5b are opsonins

d. The membrane attack complex is made up of C5b, C6, C7, C8 and C9

e. CD59 activates the membrane attack complex

a. Is the primary antibody found in mucosal secretions

b. Can cross the placenta

c. Can be one of eight subclasses

d. Is secreted by T cells

e. All of the above

34. Antigen presenting cells:

a. Activate cytotoxic T cells

b. Internalize antigens from the extracellular space

c. IInclude dendritic cells, macrophages, and B-cells

d. All of the above

35. Leukoran is a member of which drug class?

b. Alkylating agents

c. Antimetabolites

d. Anthracyclines

e. Topoisomerase inhibitors

37. Which of the following drugs is fatal when given intrathecally

d. Methotrexate

e. None of the above

38. Which of the following drugs is cardiotoxic:

c. Methotrexate

39. Which of the following drugs may cause peripheral neuropathy?

c. Daunorubicin

40. Which of the following drugs is NOT a part of the chemotherapy regimen–ABVD?

e. Cyclophosphamide

41. Which drug(s) may cause respiratory distress?

II. Cyclophosphaide

III. Daunorubicin

e. I, II, and III

42. Which of the following best describes the mechanism of action of Anzemet?

a. 5-HT3 antagonist

b. Histamine antagonist

c. Beta-2 antagonist

d. Alpha-2 antagonist

e. None of the above

43. Which of the following are considered mitotic inhibitors?

e. I, II, and III

44. Although it may be useful in control of metastatic ovarian cancer, this topoisomerase I inhibitor’s dose-limiting adverse effects include: neutropenia, thrombocytopenia, and anemia.

a. Vincristine (Oncovin)

b. Topotecan (Hycamtin)

c. Doxorubicin (Adriamycin)

d. Mitomycin (Mutamycin)

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