Cancer Chemotherapy

What is a tumor?

abnormal growth of cell tissue

Malignancies are classified based on location and tissue type such as...

-carcinoma (epithelial tissue)

-sarcoma (CT tissue)

-blood cancers ending in -emia

What is cytotoxic strategy? What is the goal? How is this done?

-basic strategy to limit cell proliferation by killing or attenuating growth of cancerous cells

-goal = selective toxicity of neoplastic cells

-methods: disrupt DNA & RNA function; inhibit mitosis of cell

What is growth fraction?

percentage of proliferating cells relative to total neoplastic cell population

-cells in growth fractions are more susceptible to medication

-these cells must be killed to prevent spread of cancer

What is the cell kill hypothesis?

with each round of chemo, it will kill a certain percentage of cancerous cells

T or F: Chemo will never completely eliminate a tumor

True

What are the different chemotherapy drug groups?

1. alkylating agents

2. antimetabolites

3. antibiotics

4. platinum drugs

5. antimicrotubules

6. topoisomerase inhibitors

7. hormones

8. targeted / biological treatments

9. miscellaneous

How do alkylating agents work?

-bind to DNA bases

-prevents DNA replication / translation

-ultimately breaks DNA chain

-releases enzyme to destroy cell

How do antimetabolites work?

-act on pathways for DNA synthesis

-interfere with normal metabolites by inhibiting enzymes and acting as fake ingredients during biosynthesis

What are adverse effects of antimetabolites?

-blood disorders

-CV toxicity

-respiratory toxicity

-fever

-skin rash

-hematuria

-GI distress

-hepatotoxicity

Why is hepatotoxicity as a side effect such a big deal?

can affect metabolism in general, as well as metabolism of other drugs

What do anticancer antibiotics do?

-high toxicity levels

-mechanism of action not well understood (may act directly on DNA)

What are adverse effects of anticancer antibiotics?

-blood disorders

-cardiotoxicity

-GI distress

-allergic rxn

-fever

-back pain / muscle pain

-pulmonary toxicity

-skin disorders

-mucosal lesions

How do platinum coordination complexes work?

-drugs contain platinum (heavy metal)

-act like alkylating agents and form strong cross-links between and within DNA strands --> prevents DNA strand translation and replication

What are platinum coordination complexes important for treating?

testicular, ovarian, and bladder cancers

What are adverse effects of platinum coordination complexes?

-blood disorders

-nephrotoxicity

-GI dstress

-anaphylactoid rxns

-peripheral neuropathies

How do antimicrotubule agents work?

-mitotic apparatus must function at specific times & rates to diret cell division --> anticancer drugs bind to microtubules, impairing mitotic apparatus and therefore affects cell division

-can inhibit formation of microtubules or the breakdown of microtubules

What are adverse effects of antimicrotubule agents?

-blood disorders

-GI distress

-hair loss

-neurotoxicity

-local irritation at injection site

-cardiopulm toxicity

-muscle/joint pain

-skin problems

How do topoisomerase inhibitors work?

-inhibit enzyme (needed for normal DNA replication)

-results in break of DNA chain and ultimately cell death

What are adverse effects of topoisomerase inhibitors?

-blood disorders

-GI distress

-allergic reactions

-neurotoxicity

-respiratory toxicity

-CNS toxicity

-fever

-skin rxns

-hair loss

How do anti-cancer hormones work?

-cancers may be hormone sensitive (exacerbated or attenuated by certain hormones)

-adreno-corticosteroids and sex hormones may influence proliferation of certain tumors

-drugs either mimic or block effects of hormones to treat certain forms of cancer

-used ad adjuvant therapy usually

-can decrease sx of advanced breast, prostate, and endometrial cancer

What is the difference between targeted and biological therapist?

targeted = week out and inhibit specific characteristics of cancer cells

biological = encourage body's immune system to deal with cancer cells

What are the 3 subtypes of targeted/biological therapies?

1. monoclonal antibodies

2. cytokines

3. tyrosine kinase inhibitors

What are MABs?

monoclonal antibodies; type of targeted and biological therapy

How do MABs work?

-cell cloning techniques manufacture antibodies that bind to specific antigen on surface of tumor cells

-after binding, blocks signal that causes mitosis

-initiates programmed cell death

-sensitizes cancer cells to an attack from T lymphocytes

-inhibits angiogensis

What are adverse effects of MABs?

-Gi distress

-metabolic imbalances

-skin rash

-intestinal obstruction

-infection

-ocular toxicity

-CV toxicity

-fever

What is the suffix for MABs?

-mab

How do cytokines work? What are their effect?

-small proteins that stimulate immune mechanism that normally deal with abnormal cell proliferation

-2 strategies: interferons and interleukins

-effect: activate signals to inhibit cell division & promote cell death; direct cytotoxic immune cells to attack cancer cells

What do kinase inhibitors do?

-cancerous cells may have defective kinase to lead to uncontrolled cell proliferation

-inhibits abnormal kinase that are involved in cell signaling and regulation of cell division to limit cell proliferation

What are adverse effects of kinase inhibitors?

-GI distress

-interstitial lung disease

-skin rash

-pulmonary toxicity

-allergic rxn

-blood disorders

-hepatotoxicity

-joint and muscle pain

What are combination chemotherapy agents?

-when several anticancer drugs are used simultaneously

-increases chances of successful tx because of additive and synergistic effects of each agent

-acronym of drug names

What are chemotherapy side effects?

-hair loss

-GI problems

-anemia

-fatigue

-neurotoxicity / cardiotoxicity

-skin rashes

-otherssss

What are rehab considerations with cancer tx?

-pt support and reassurance

-pain reduction

-maintain & improve strength, ROM, CV function as indicated

-neutropenic precautions & other reduced blood values

-fluid & electrolyte disorders

-infections

-cancer associated thrombosis

-nutrition

-chemotherapy-induced neuropathy

Current success is limited in certain cancers including...

-lung

-colon/rectal

-breast

-prostate

What are strategies to prevent or overcome resistance to drugs?

-alter dosage, timing, delivery methods, sequence of administration

T or F: There is a need for more, better tolerated cancer therapies that protect healthy cells from chemo drugs

True dat