Introduction to Chemotherapy Flashcards
What is chemotherapy?
Any treatment involving the use of chemical agents in the treatment of cancer
Use of cytotoxic drugs, targeted agents, and hormone
SYSTEMIC treatment
Delivered intravenously (usually), circulates through the body in the bloodstream and kills cancer cells along with healthy cells, anywhere in the body, including those at great distances from original site
Chemotherapy usually affects whole body
What are the 3 intents of chemotherapy?
- Cure – complete remission for > 5 years
- Control – partial or temporary remission
- Palliate – relieve symptoms
Primary Modality
Chemotherapy can be used alone as a primary treatment modality (common for hematologic cancers) ex: leukemia
Adjuvant
Chemotherapy given in addition to (after) the primary modality (surgery or radiation)
Assuming there are cells left behind that we can’t see and chemotherapy is delivered to kill those remaining unseen cancer cells
Neoadjuvant
Chemotherapy is given BEFORE another modality (surgery or radiation)
With intent to shrink the tumor so less extensive surgery is needed or to reduce the volume of tissue requiring irradiation or to kill small deposits of cancer cells that cannot be seen on scans
Concurrent (concomitant)
Chemotherapy given at the same time as another modality
Induction Chemotherapy
Upfront chemotherapy in the absence of surgery
Chemo Catch-22
Most chemotherapy drugs cannot tell the difference between a cancer cell and a healthy cell (thus poisons most cells it comes into contact with)
**Intent of balancing the destruction of cancer cells (in order to cure or control the disease) while sparing normal cells
Chemotherapy is most effective against cells that are rapidly dividing
- Blood cells
- Hair
- Mucous membranes (mouth, throat, intestines)
- Cancer cells
What is Combination Chemotherapy?
Use a combination of drugs (combination therapy) vs. single agent treatment
Each agent (drug) has different way of working/mechanism of action and is effective are specific time in the life of the cell it is meant to act on
Combination of drugs allows for each medication to enhance the action of the other or act as synergistically
Advantages of Combination Therapy?
- Increased cell kill
- Prevention and counteraction of drug resistance
- synergistic effects allow for lower doses and, subsequently, for some combinations, less toxicity
- Different mechanisms of action
Review of the Cell Cycle
Interphase
- G1 - cell increases supply of protein, number of organelles, and gowns in size
- S - DNA is replicated
- G2 - cell continues to grow, control mechanism to ensure entrance to mitosis
Mitosis – cell divides into 2 daughter cells
What is Cell cycle phase specific?
Cell cycle phase specific = act on cells during certain phases of the cell cycle and, therefore, need prolonged exposure or repeated doses
What is Cell cycle phase non-specific?
act on cells at ANY phase of the cell cycle, including those in G0
Cell Kill Hypothesis
EVERY tumor cell must be killed to cure each cancer
Repeated courses of chemo used to reduce the total number of cells
Cardinal rule of chemo: There is an Inverse relationship between cell number and curability (the more cells in a tumor, the less likely to cure)
How is Chemotherapy dosed?
- Drug dependent
- Age dependent
- Patient weight in kilograms (1 kg = 2.2 lbs)
Chemo doses are determined based on body surface area (BSA), which is calculated by using height and weight
Dosing is different for children and elderly as their bodies process drugs differently
Chemo Scheduling
Chemo is given at regular intervals (cycles)
Chemo cycle may involve a dose of 1 or more drugs followed by several days or weeks without treatment = gives time for normal cells to recover from damage and patient time to recover from drug’s side effects
Some drugs work best when given continuously over a set number of days
Drug given on a schedule carefully coordinated to maximize drug’s tumor cell kill and planned to allow normal cells to recover
Chemo Scheduling continued
- It is important, when possible to get the full course of chemo and to keep the cycles on schedule, as it gives the best change to get maximum benefit from treatment
Chemo Dosing Listings
-
Standard dose therapy
- usual adult dose administered for most patients
-
High dose delivery
- increased drug dose (more severe side effects)
-
Dose intensity
- drug administered at a great dose than standard and at shorter intervals
-
Dose density
- increased drug dose and combination of varied drugs
Method of administration: Intravenous (IV)
Common method of administration
Injected via infusion/drip (mixed drug solution from plastic bag flows through tubing attached to the catheter) or IV push (drug given quickly into the catheter via a syringe)
Method of Administration: Oral
Easiest method
Requires full patient compliance in taking the drugs AND taking the drugs at the right times
Central lines
Reasons for central line:
- given several drugs at one time
- reduce number of needle sticks in peripheral veins in case of long-term therapy
- less wear and tear to the veins for frequent treatments
- continuous infusion chemo
- delivering vesicants (drugs that cause damage to skin and muscle) to reduce risk of drug leaking outside the vein and damaging tissues
PICC Line (peripherally inserted central catheter)
- Inserted in vein of arm and threaded up near the heart
- Immediate-length therapy
- Continuous access for several weeks to months
Midline catheter
- Placed in vein in the arm and threaded towards the heart BUT not as far as PICC
- Immediate length therapy or when short-term IV is not advisable or available
Tunneled central venous catheter (Hickman line)
- Surgically placed in large central vein in the chest
- Catheter is tunneled under the skin, but openings to the lumens remain outside the body
- Long-term catheter that is good for months to years
Implantable venous access port (Port-A-Cath)
- Drum-shaped port of plastic, stainless steel, or titanium with a silicone septum across the top
- Surgically placed under the skin of the chest, or upper arm
- Catheter extends into a large or central vein
Methods of Administration: Intrathecal
- Infusion into the central nervous system via cerebrospinal fluid
- Delivered through a lumbar puncture (spinal tap) or a device placed under the scalp (Ommaya reservoir)
Methods of Administration: Intraperitoneal
- Infused via a catheter into the abdomen around the intestines and other organs
- Sometimes done during surgery
Methods of Administration: Intra-arterial
- Injected into artery that goes to certain area of the body
- Most commonly used for liver or cancer that has spread to the liver
Extravasation
def: the leakage of a drug from the IV line into surrounding tissue
May occur when:
- when peripheral catheter erodes through vessel wall
- when increased venous pressure causes leakage around the venipuncture site
- when needle pulls out of a vein
Signs and symptoms of Extravasation
- Edema
- Changes in the site’s appearance
- Change in temperature (blanking or coolness)
- Feeling of tightness around the site
Extravasations continued
Vesicant drugs or solutions can cause severe tissue injury or destruction if they escape from the vein
Consequences include:
- Necrotic ulcers
- Infection
- Disfigurement
- Complex regional pain syndrome
- Loss of function
Extravasations: When vesicant drugs extravasate
- Discontinue line
- Apply cool compress
- Administer antidote if one exits
- Consult plastic surgery if:
- tissue is discolored, tense, blistering,
- patient reports severe pain
- decrease peripheral pulse
- > 25 mL medication escaped into tissue
What are the 6 classifications of chemo drugs?
- Alkylating agents
- Antitumor antibiotics
- Antimetabolites
- Miotic inhibitors
- Vinca alkaloids
- Taxanes
- Nitrosureas
- Epipodophyllotoxins
Alkylating Agents
- Oldest and most common type
-
Cell cycle phase non-specific
- effective in all phases of cell cycle; best at treating slow-growing cancers
Mechanism of action – attaches an alkyl group to guanine based of the DNA molecule, thereby preventing its replication by making the strands of DNA unable to uncoil and separate
Classic Alkylating Agents
- Carboplatin
- Cisplatin
- Cyclophosphamide
- Oxaliplatin
- Ifosfamide
Alkylating Agents
Used to treat many different cancers BUT because these drugs damage DNA and potentially damage the bone marrow, they can cause long-term damage and in rare cases, may lead to leukemia in future (secondary malignancy)
Clinical toxicities include:
- bone marrow depression
- anemia
- leukemia
- thrombocytopenia
- gonadal dysfunction
- ototoxicity
- hemorrhagic cystitis
- hair loss
Alkylating Agents: Carboplatin
Ovarian cancer
Alkylating Agents: Cisplatin
H&N cancers
High risk NV and tinnitus
Alkylating Agents: Cyclophosphamide
Breast cancer and lymphomas
High risk for hemorrhagic cystitis
Alkylating Agents: Oxaliplatin
Colon cancer
Patients tend to wear gloves and avoid cold substances, as they are very temperature sensitive
Alkylating Agents: Ifosfamide
Sarcoma, testicular, lymphomas
High risk of hemorrhagic cystitis; must be given Mesna
Antitumor Antibiotics
Cell cycle phase non-specific
Mechanism of action – Block DNA and RNA synthesis by DNA intercalation
Classic Antitumor Antibiotics
- Adriamycin (doxorubicin) “Red devil” breast cancer
- Daunorubicin – AML
- Bleomycin – H&N cancer, lymphoma
- Mitomycin-C – Anal cancer
Antitumor Antibiotics side effects
Common side effects include low blood counts, mouth sores, fatigue, decreased appetite
What are anthracyclines?
Type of antitumor antibiotics that interfere with enzymes involved in DNA replication
- permanently damage the heat (and other organs) if given high doses, therefore lifetime dose limits are placed for these drugs
Common Anthracyclines:
- Daunorubicin
- vesicant
- results in urine discoloration and alopecia
- Adriamycin (doxorubicin)
- vesicant
- cardiotoxicity, myelosuppression
- radiation recall
- Bleomycin
- pulmonary toxicity
- hypersensitivity/anaphylaxis
Antimetabolites
Cell cycle phase specific – S phase of the cell cycle
Interfere with DNA and RNA by masquerading the normal building blocks of RNA and DNA or by inhibiting enzymes needed for nucleic acid production
Antimetabolites common side effects:
- NV
- ulcers
- loss of appetite
- lover damage
- kidney failure
- hair loss
- fatigue
- fever
- low WBC
Antimetabolites: 5-Fluorouracil (5-FU)
Radiosensitizer
GI cancers
Antimetabolites: Cytarabine
AML, CNA lymphoma
Cerebellar toxicity with high doses
Antimetabolites: Methotrexate
NHL
Requires Leucovorin rescue due to risk of RBC destruction
Antimetabolites: Capecitabine (Xeloda)
GI cancers
Recurrent breast cancer
Antimetabolites: Cytarabine
Head and food syndrome
Antimetabolites: Gemcitabine
Pancreatic cancer
Myelosuppression
Mitotic Inhibitors
Cell cycle specific agents – work during M phase of cell cycle but can damage cells in all phases
Stop or inhibit mitosis by disrupting the microtubules (structures that pull cell apart when it divides)
Mitotic Inhibitors: Vinca Alkaloids
Cell cycle phase specific
Navelbine
Vinblastine
Vincristine
