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Module 8: Cancer Chemotherapy

Tasks

Study tip: For each chapter, read "Special Concerns for Rehabilitation Patients" and "Case Study" prior to chapter
content. Answer the case study questions while you read the chapter, then compare your answers to Appendix C.
Ch 36 (Cancer Chemotherapy)

As you read this chapter, track frequency to determine the most common adverse effects for cancer drugs in the
medication cabinet: template file.

Medication Cabinet
cyclophosphamide (Cytoxan, Neosar)
fluorouracil (Adrucil)
methotrexate (Generic when used for cancer)
doxorubicin (Adriamycin)
paclitaxel (Taxol)
prednisone
tamoxifen
interferon alfa-2b (Intron-A)
cisplatin (Platinol)
hydroxyurea (Hydrea)

Assessment
Cancer Chemotherapy module is included in Examination 2 on Dec. 8. Practice questions are available.

Learning Objectives

1. Describe principles of "cytotoxic strategy", "cell-cycle specific"/nonspecific, "growth rate", "cell kill
hypothesis", "therapeutic index", and "combination chemotherapy" for cancer treatment.
1. Cytotoxic strategy-
1. Basic strategy is to limit cell proliferation by killing or attenuating the growth of the cancerous cells
2. However, these cells cannot be easily destroyed without also causing harm to healthy human
tissue (concept of selective toxicity becomes more difficult to achieve)
3. Most anticancer drugs rely on the basic strategy of:
1. inhibiting DNA/RNA synthesis and function or on directly inhibiting cell division (mitosis)
1. cancerous cells have a greater need to
replicate their genetic material and thus
undergo mitosis at a much higher rate
than most noncancerous cells so
anticancer drugs will affect cancerous
cells to a greater extent
2. Cell-cycle specific- cell-cycle specific drugs exert their effects only
when the cancer cell is in a certain phase of its life cycle
1. Most antimetabolites act when the cell is in the S phase
(period of DNA synthesis)
2. These drugs are only effective in cells that are
progressing through the cell cycle (cells that are not
remaining in the nondividing (G0) Phase)
3. Cell-cycle nonspecific- they exert antineoplastic effects on the cell
regardless of the cell cycle’s phase
1. Most alkylating agents and antineoplastic antibiotics
2. These drugs have more general effect and should inhibit Antimetabolites
replication in all cells the drug reaches
cyclophosphamide
4. Growth fraction- refers to the percentage of proliferating cells relative to total neoplastic cell population
1. Cells in the growth fraction are more susceptible to antineoplastic drugs because these cells must
synthesize and replicate their genetic material
2. Growth fraction typically decreases as a tumor gets bigger- that is the percentage of cells that are
actively dividing starts to decline as the tumor gets larger because blood flow and nutrient supply
to the tumor cannot sustain extremely rapid tumor growth
5. Cell kill hypothesis- based on the idea that each round of chemotherapy will kill a certain percentage of
cancerous cells
1. Thus, if chemotherapy regimen kills 90% of tumor cells, 10% of the tumor cells will survive each
round of chemotherapy
2. According to this theory, chemotherapeutic regimen can never completely eliminate the tumor
because some % of cells will remain alive after each round of treatment
6. Therapeutic index- antineoplastic drugs typically have a very low TI compared with drugs that are used to
treat less serious disorders
1. Most cancer chemotherapy agents will also affect the healthy tissues to some extent and this is
the primary reason for most of the common adverse effects (hair loss, anemia, nausea) is that
normal cells are also experiencing the same toxic changes as the tumor cells
2. Healthy cells often exhibit some toxic effects, even at the minimum effective dose of the
chemotherapeutic agents
3. Considering that cancer is usually life-threatening, these toxic effects must be expected and
tolerated during chemotherapeutic treatments
7. Combination chemotherapy-
1. General strategy is in line with using multiple anticancer modalities (surgery, radiation and a
combination of several different antineoplastic drugs)-necessary to achieve successful outcome?
2. In addition, a multimodal approach (combining chemotherapy with radiation or using several
drugs simultaneously) may produce a synergistic effect between these modalities
1. Often different types of anticancer drugs are combined in the same regimen
1. A particular drug regimen may include an alkylating agent, an antineoplastic
antibiotic, a hormonal agent, or other combo (usually indicated by an acronym)

Breast Cancer combination treatments:


FAC= fluorouracil, doxorubicen, cyclophosphamide
CMF= cyclophosphamide, methotrexate, fluorouracil

2. Define clinical types of chemotherapy: primary induction, neoadjuvant, adjuvant.


1. Primary induction- first-line treatment to induce remission
1. in many situations, chemotherapy may be the primary or sole form of treatment in neoplastic
disease, especially for certain advanced or inoperable tumors or in widely disseminated forms of
cancer such as leukemia or lymphoma
2. Neoadjuvant- chemotherapeutic agents can be administered prior to a more aggressive surgical or
radiation treatment
1. Can help control or reduce the cancerous growth so that the nondrug intervention is more
successful in eliminating the cancer
3. Adjuvant- additional cancer treatment given after the primary treatment to lower the risk that the cancer
will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy,
targeted therapy, or biological therapy
1. Using anticancer drugs following a mastectomy or surgical removal of other carcinomas
3. Explain the clinical relevance of "resistance" to anticancer drugs.
1. Cancers may develop resistance to a broad range of chemotherapeutic agents (multiple drug resistance)
2. Cancer has become resistant to drugs through several different mechanisms
1. Occurs when the cancer cell synthesizes a glycoprotein that acts as a drug efflux pump
1. The glycoprotein pump is inserted into the cancer cell’s membrane and effectively expels
different types of anticancer drugs from the cancer cell before the drugs have a chance to
exert cytotoxic effects
2. Cancer cells can induce drug resistance through the production of enzymes and specific
substances (glutathione, glutathione-S-transferase) that inactivate anticancer drugs within the
cancer cell
3. Cells can also develop mechanisms that repair DNA damaged by anticancer drugs such as the
alkylating agents and platinum complex drugs
4. Many anticancer drugs must bind to a specific receptor on or within the cancer cell
1. These cells can develop drug resistance by modifying the structure or function of these
receptors so that the drug is unable to bind to the receptor
3. Strategies are being explored to prevent or overcome multiple-drug resistance during cancer
chemotherapy
1. Altering the dosage, timing, delivery methods, and sequence of administration of different
medications

4. Identify adverse effects that are common to many cancer chemotherapy drugs; determine lab values that
should be monitored for adverse effects.
1. Anemia (microcytic anemia)
1. Hematocrit: 37-49% (men) and 36-46% for (women)
2. Hemoglobin: 13-18 (men) and 12-16 (women)
1. anemia is seen when it drops below 13.5 in men and below 12 in women
3. RBC count: 4.5-5.3 (male); 4.1-5.1 (females)
1. Would see low RBC count
4. Mean corpuscular volume (MCV): 80-94 (decreased MCV- small cells)
2. Leukopenia/neutropenia (white blood count)
1. WBC: 4,500-11,000 (normal)
2. leukopenia- decreased leukocytes (< 5000/ml- no exercise)
-neutrophils (1800-7000 is normal with 50-60 differential)
-neutropenia is decreased levels (<1500)
3. Thrombocytopenia (low platelet count)
1. CBC of fewer than 150,000 platelets
1. Normal is 150,000-400,000; concerning when they drop below 20,000- no exercise
4. GI distress (N/V, loss of appetite, diarrhea, ulcer)
5. Skin distress (hair loss, rash)