CHEMO

Question 1

An anticancer agent that acts on tumor stem cells when they are traversing the cell
cycle and when they are in the resting phase.

Answer 1

Cell cycle-nonspecific (CCNS) Drug

Question 2

An anticancer agents that acts selectively on tumor stem cells when they are traversing the cell cycle and not when they are in the G0 phase.

Answer 2

Cell cycle-specific (CCS) Drug

Question 3

The proportion of cells in a tumor population that are actively dividing

Answer 3

Growth fraction

Question 4

A drug that suppresses the formation of mature blood cells such as erythrocytes,
leukocytes, and platelets. This effect is also known as “bone marrow suppression.”

Answer 4

Myelosuppressant

Question 5

A mutant form of a normal gene that is found in naturally occurring tumors and which, when expressed in noncancerous cells, causes them to behave like cancer cells.

Answer 5

Oncogene

Question 6

Act with first-order kinetics. A given dose kills a constant proportion of a cell population rather than a constant number of cells.

Answer 6

Cytotoxic Drugs

Question 7

Proposes that the magnitude of tumor cell kill by anticancer drugs is a logarithmic
function.

Answer 7

Log-Kill Hypothesis

Question 8

There is an inverse relationship between tumor cell number and curability.

Answer 8

Hematologic malignancies

Question 9

Most do not grow in an exponential manner; rather, the growth fraction of the tumor decreases with time owing to blood supply limitations and other factors.

Answer 9

Solid tumors

Question 10

The response to chemotherapy depends on where the tumor is in its growth curve.

Answer 10

Drug-sensitive solid tumors

Question 11

Changes in drug sensitivity and increased synthesis of target enzyme, dihydrofolate reductase

Answer 11

Methotrexate

Question 12

Increased activity of enzymes capable of inactivating anticancer drugs

Answer 12

Purine and pyrimidine antimetabolites

Question 13

• Drug therapy as primary treatment
• Many hematologic cancers
• Advanced solid tumors for which no alternative treatment exists
• Curative in a small number of patients with advanced metastatic disease (eg. lymphoma, acute myelogenous leukemia, choriocarcinoma, and several childhood
  cancers)
• In many cases the goals of therapy are:
  > Palliation of cancer symptoms
  > Improved quality of life
  > Increased time to tumor progression

Answer 13

Primary Induction Chemotherapy

Question 14

• Use of chemotherapy in patients who present with localized cancer for which alternative local therapy, such as surgery, exist.
• Goal:
  > To render the local therapy more effective

Answer 14

Neoadjuvant chemotherapy

Question 15

• Used in the treatment of many solid tumors
• Chemotherapy serves as an important adjuvant to local treatment procedures such as surgery or radiation.
• Goals:
  > To reduce the risk of local and systemic recurrence
  > To improve disease-free and overall survival

Answer 15

Adjuvant Chemotherapy

Question 16

Benefits of Combination Therapy

Answer 16

• Increases log-kill markedly
• Synergistic effects in some cases
• Often cytotoxic to a heterogeneous population of cancer cells
• May prevent development of resistant clones

Question 17

• Dexrazoxane
• Inhibits free radical formation
• Affords protection against the cardiac toxicity of these agents

Answer 17

Anthracyclines (eg. doxorubicin)

Question 18

• Leucoverin
• Form of tetrahydrofolate that is accumulated more readily by normal than by neoplastic cells.
• Results in rescue of the normal cells.

Answer 18

Methotrexate

Question 19

• Mercaptoethanesulfonate (mesna)
• “Traps” acrolein released by cyclophosphamide
• Thus reduces incidence of hemorrhagic cystitis

Answer 19

Cyclophosphamide

Question 20

• are CCNS drugs.
• Form reactive molecular species that alkylate nucleophilic groups on DNA bases, particularly the N-7 position of guanine.
• Leads to cross-linking of bases, abnormal base-pairing, and DNA strand breakage.

Answer 20

Alkylating Agents

Question 21

• Hepatic cytochrome P450-mediated biotransformation is needed for antitumor
  activity.
• One of the breakdown products is acrolein.
• Expected adverse effect includes GI distress, myelosupression, and alopecia

Answer 21

Cyclophosphamide

Question 22

Clinical Use of Cyclophosphamide

Answer 22

• leeukemia
• Non-Hodgkin’s Lymphoma
• Breast and Ovarian cancers
• Neuroblastoma

Question 23

Cyclophosphamide Toxicity

Answer 23

• hemorrhagic cystitis from formation of acrolein
• cardiac dysfunction
• Pulmonary toxicity
• Syndrome of inappropriate antidiuretic hormone (ADH) secretion

Question 24

• Spontaneously converts in the body to a reactive cytotoxic product
• Best known for use in: Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma
• common toxic effects includes GI distress, myelosupression, alopecia, and sterility

Answer 24

Mechlorethamine

Question 25

- Used intravenously | - The drugs distribute to most tissues and are cleared in an unchanged form by the kidney

Answer 25

Platinum Analogs (Cisplatin, Carboplatin, Oxaliplatin)

Question 26

- commonly used for testicular carcinoma and cancers of the bladder, lung, and ovary - used in advanced colon cancer

Answer 26

- Cisplatin & Carboplatin | - Oxaliplatin:

Question 27

Cisplatin Toxicity

Answer 27

- GI distress - Mild hematotoxicity - Neurotoxic (peripheral neuritis and acoustic nerve damage) - Nephrotoxic - may be reduced by use of mannitol with forced hydration

Question 28

Carboplatin Toxicity Oxaliplatin Toxicity

Answer 28

- Less nephrotoxic than cisplatin - Less likely to cause tinnitus and hearing loss - Greater myelosuppressant actions - Dose-limiting neurotoxicity

Question 29

- A reactive agent that forms hydrogen peroxide, which generates free radicals that cause DNA strand scission. - Orally active - Penetrates into most tissues, including the CSF - Eliminated via hepatic metabolism - Use. for Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Brain tumors

Answer 29

Procarbazine

Question 30

Procarbazine Toxicity

Answer 30

- Myelosuppressant - GI irritation - CNS dysfunction - Peripheral neuropathy - Skin reactions - Inhibits many enzymes in including monoamine oxidase and and those involved in hepatic drug metabolism. - Disulfiram-like reactions have occurred with ethanol - Leuokemogenic

Question 31

Sometimes used in chronic myelogenous leukemia | - Causes adrenal insufficiency, pulmonary fibrosis, and skin pigmentation

Answer 31

Busulfan

Question 32

- Other alkylating drugs that is highly lipid-soluble and used in brain tumors - Hodgkin's Lymphoma. Causes alopecia, skin rash, GI distress, myelosuppression, phototoxicity, and a flu-like syndrome

Answer 32

- Carmustine & Lomustine | - Dacarbazine

Question 33

- Structurally similar to endogenous compounds - Antagonists of folic acid (methotrexate), purines (mercaptopurine, thioguanine), or pyrimidines (fluorouracil, cytarabine, gemcitabine). - CCS drugs acting primarily in the S phase of the cell cycle. - Cytotoxic effects on neoplastic cells - Immunosuppressant

Answer 33

Antimetabolites

Question 34

- Inhibitor of dihydrofolate reductase - This leads to decreased synthesis of thymidylate, purine nucleotides, and amino acids and thus interferes with nucleic acid and protein metabolism. - The formation of polyglutamate derivatives of methotrexate appears to be important for cytotoxic actions. - Decreased drug accumulation - Changes in drug sensitivity or activity of dihydrofolate reductase - Decreased formation of polyglutamates

Answer 34

Methotrexate

Question 35

Clinical Use of Methotrexate: - Effective in: - Solid tumors - other uses

Answer 35

Effective in: - Choriocarcinoma - Acute leukemias - Non-Hodgkin's and Primary - CNS lymphomas Solid tumors: - breast cancer, - head and neck cancer, and - bladder cancer Other uses: - rheumatoid arthritis - psoriasis & - ectopic pregnancy

Question 36

Methotrexate Toxicity Common: Leocovarin Rescue: Long Term Use:

Answer 36

Common - bone marrow suppression - Toxic effects on the skin and GI mucosa (mucositis) Leucovarin Rescue - toxic effect of methotrexate on normal cells may be reduced by administration of folinic acid (leucovorin). Long-Term Use - Hepatotoxicity - Pulmonary infiltrates and fibrosis

Question 37

- Purine antimetabolites - Activated by hypoxanthine-guanine phosphoribosyltransferases (HGPRTases) to toxic nucleotides that inhibit several enzymes involved in purine metabolism. - Decreased activity of HGPRTase - Increase production of alkaline phosphotases that inactivate the toxic nucleotides - Low oral bioavailability because of first-pass metabolism by hepatic enzymes

Answer 37

Mercaptopurine (6-MP) and Thioguanin (6-TG)

Question 38

Main Clinical Use of Mercaptopurine (6-MP) and Thioguanin (6-TG)

Answer 38

- Acute leukemias | - Chronic myelocytic leukemia