Oncology

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CHAPTER 17 Oncology

I. Definitions

A. Cancer: Typically defined as a group of diseases characterized by uncontrolled and abnormal local cellular growth, local tissue invasion, and distant spread to other locations (metastases).
B. Second to cardiovascular disease for all-cause mortality
C. Etiology

1. Carcinogenesis: process by which normal mechanisms for control or growth and proliferation of cells are altered

a. Initiation: exposure of normal cells to a carcinogenic substance
b. Promotion: alteration of environment to favor growth of mutated cell over normal cells
c. Progression: genetic changes leading to cell proliferation, invasion, and development of metastasis

II. Risk factors

A. Environmental

1. Radiation
2. Virus

B. Occupational

1. Asbestos
2. Benzene, chromium, nickel

C. Lifestyle

1. Tobacco
2. Alcohol
3. Diet

III. Principles of tumor growth

A. Tumor growth is exponential.
B. Chemotherapy kills a certain percentage of cells, not a particular number.
C. Metastasis

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

a. Spread by blood and lymphatic pathways

IV. Cancer sites and types include, but are not limited to:

A. Acute myeloid leukemia (AML)
B. Bladder cancer
C. Bone cancer
D. Breast cancer
E. Chronic myelogenous leukemia (CML)
F. Central nervous system cancers
G. Kidney cancer
H. Colon and rectal cancer
I. Ovarian cancer
J. Cervical cancer
K. Prostate cancer
L. Gastric cancer
M. Head and neck cancers
N. Hepatobiliary cancers
O. Melanoma
P. Multiple myeloma
Q. Myelodysplastic syndromes
R. Neuroendocrine tumors
S. Hodgkin and non-Hodgkin lymphomas
T. Nonmelanoma skin cancers
U. Occult primary
V. Pancreatic adenocarcinoma
W. Soft-tissue sarcoma
X. Thymic malignancies
Y. Thyroid carcinoma
Z. Uterine neoplasms
AA. Testicular cancer

V. Prevention and screening

A. Breast

1. Women 40 years and older should have an annual mammogram and clinical breast exam by a health-care professional; individuals should perform monthly self-examinations.

B. Colon/rectum

1. Persons 50 years and older should have at least one of the following: colonoscopy, fecal occult blood test, flexible sigmoidoscopy, or double contrast barium enema; combination testing is preferred. Earlier screening examination is recommended in those with familial risk factors.

C. Prostate

1. Men 50 years and older should have a prostate-specific antigen (PSA) test and digital rectal exam annually.

D. Cervix

1. Women 18 years and older or who are sexually active should have Pap test and pelvic exam annually.

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

A. Surgery
B. Radiation
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

B. Cell cycle actions of chemotherapy

1. Many drugs are cell cycle specific.
2. Phases

a. G1 phase

(1) Manufacture necessary enzymes for DNA synthesis

b. S phase

(1) DNA replication

c. G2 phase

(1) Cell prepares for mitosis after DNA synthesis.

d. M phase

(1) Mitosis (cell division)

e. G0 phase

(1) Resting phase

C. Common routes of chemotherapy administration

1. Oral
2. Intravenous (IV)
3. Intrathecal
4. Intracavitary
5. Intra-arterial

D. Classification of chemotherapeutic agents

1. Alkylating agents

a. Nitrogen mustards

(1) Examples: cyclophosphamide, ifosfamide, mechlorethamine, thiotepa, melphalan, chlorambucil

b. Nitrosoureas

(1) Examples: carmustine (BCNU), lomustine (CCNU)

c. Platinum compounds

(1) Examples: cisplatin, carboplatin, oxaliplatin

d. Miscellaneous

(1) Examples: busulfan, dacarbazine, temozolomide, procarbazine

2. Antimetabolites

a. Folic acid analogs

(1) Example: methotrexate

b. Pyrimidine analogs

(1) Examples: fluorouracil (5-FU), capecitabine, cytarabine, gemcitabine, floxuridine, tegafur/uracil

c. Purine analogs

(1) Examples: mercaptopurine, cladribine, fludarabine, thioguanine, pentostatin

3. Plant alkaloids

a. Vinca alkaloids

(1) Examples: vincristine, vinblastine, vinorelbine, vindesine

b. Podophyllotoxins

(1) Examples: etoposide, teniposide

c. Taxanes

(1) Examples: paclitaxel, docetaxel

d. Camptothecins (topoisomerase inhibitors)

(1) Examples: irinotecan, topotecan

4. Antibiotics

a. Anthracycline antibiotics

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

b. Miscellaneous

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

5. Biologic Response Modifiers

a. Monoclonal antibodies

(1) Examples: rituximab, trastuzumab, gemtuzumab ozogamicin, alemtuzumab, cetuximab, bevacizumab

b. Monoclonal antibody/radiopharmaceuticals

(1) Examples: tositumomab 131I, ibritumomab tiuxetan 90Y

c. Miscellaneous

(1) Examples: interferon, interleukin-2, bacillus Calmette-Guérin (BCG)

6. Tyrosine kinase inhibitors

(a) Examples: imatinib, gefitinib

7. Miscellaneous

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

8. Hormone agents

a. Adrenocorticosteroids

(1) Examples: dexamethasone, prednisone, methylprednisolone

b. Progestins

(1) Examples: megestrol, medroxyprogesterone

c. Estrogens

(1) Examples: diethylstilbestrol, ethinyl estradiol

d. Antiestrogens

(1) Examples: tamoxifen, raloxifene, anastrozole, letrozole, exemestane, fulvestrant

e. Androgens

(1) Examples: testosterone, fluoxymesterone

f. Antiandrogens

(1) Examples: flutamide, bicalutamide, nilutamide

g. Gonadotropin-releasing hormone analog

(1) Examples: leuprolide, goserelin, triptorelin

E. Adverse effects of chemotherapy

1. Nonspecific

a. Fatigue

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

a. Neutropenia: calculate absolute neutrophil count (ANC)

image

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(1) Busulfan, carmustine, lomustine, cyclophosphamide, semustine, chlorambucil, dacarbazine, ifosfamide, carboplatin, cytarabine, fluorouracil, methotrexate, daunorubicin, doxorubicin, paclitaxel, docetaxel, topotecan, mitomycin, and others
(2) Treatment of neutropenia

(i) Filgrastim (Neupogen)

(a) Stimulates neutrophil production
(b) Dose: 5 mcg/kg per day SQ or IV; give at least 24 hours after last dose of chemotherapy

(ii) Pegfilgrastim (Neulasta)

(a) Same mechanism as filgrastim but has prolonged renal elimination and half-life
(b) Dose: 6 mg AQ once per cycle (adults only)

(iii) Sargramostim (Leukine)

(a) Used for cancer chemotherapy and bone marrow transplant
(b) Dose: 250 mcg/m2 per day SQ or IV (dose based on body surface area [BSA])

b. Thrombocytopenia

(1) Platelets <100,000
(2) Carboplatin, gemcitabine, mitomycin, BCNU, vinorelbine
(3) Treatment

(i) Transfusions
(ii) Oprelvekin (Neumega)

(a) Dose: 50 mcg/kg SQ daily; give 24–36 hours after chemotherapy

c. Anemia

(1) Cisplatin and carboplatin
(2) Treatment

(i) Recombinant human erythropoietin (EPO) (Epogen, Procrit)

(a) Used in patients with Hct <33% or Hb <11%
(b) Dose: 40,000 units SQ or IV weekly or 150 units/kg three times weekly SQ or IV; dose adjustment may be needed

(ii) Darbepoetin (Aranesp)

(a) Same mechanism as EPO and similar side effects but three times longer half-life and duration of action
(b) Dose: 200 mcg SQ every 2 weeks

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

1. Prevention
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

10. Gastrointestinal toxicity

a. Nausea/vomiting

(1) Methotrexate, fluorouracil, cisplatin, cyclophosphamide, doxorubicin, hydroxyurea, dacarbazine, nitrosoureas, cytarabine
(2) Treatment: 5-HT3 antagonists

b. Diarrhea

(1) Irinotecan, methotrexate, fluorouracil, cytarabine, dactinomycin, 5-azacytadine, hydroxyurea, nitrosoureas, cyclophosphamide
(2) Treatment

(a) Hydration, IV fluids
(b) Loperamide
(c) Octreotide
(d) Codeine

c. Constipation

(1) Vinca alkaloids

(a) Treatment: laxative or stool softener

d. Stomatitis/mucositis

(1) Bleomycin, methotrexate, fluorouracil, doxorubicin, cytarabine
(2) Treatment and prevention

(i) Antifungal agents: nystatin, fluconazole
(ii) Chlorhexidine
(iii) Magic mouthwash (various combinations including nystatin, Mylanta, viscous lidocaine, dexamethasone)

11. Hypersensitivity reactions

a. Fever

(1) Bleomycin, 5-azacytadine

b. Anaphylactic reactions

(1) Paclitaxel, docetaxel, bleomycin, etoposide, cisplatin, procarbazine, anthracyclines

c. Photosensitivity

(1) Methotrexate, fluorouracil, vinblastine, dacarbazine

d. Pigment changes

(1) Busulfan, bleomycin, doxorubicin, fluorouracil

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