Oncology Flashcards
1
Q
Antimetabolites - Available Drugs
A
- Methotrexate (MTX)
- 5-Fluorouracil (5-FU)
- 6-Mercaptopurine (6-MP)
- 6-Thioguanine (6-TG)
- Cytarabine (ara-C)
2
Q
Antimetabolites - Cell Cycle Specificity
A
All anti metabolites inhibit DNA synthesis and are thus S phase specific.
3
Q
Methotrexate (MTX) - MOA
A
- S phase specific
- Folic acid analog that inhibits dihydrofolate reductase –> Inhibit production of dTMP –> Inhibit DNA and protein synthesis
4
Q
Methotrexate (MTX) - Clinical Use
A
Cancer:
- Leukemia
- Lymphoma
- Choriocarcinoma
- Sarcoma
Non-neoplastic
- Abortion
- Ectopic pregnancy
- Rheumatoid arthritis
- Psoriasis
5
Q
Methotrexate (MTX) - Toxicities
A
- Myelosuppression - Reversible with Leucovorin (folinic acid) rescue
- Macrovesicular fatty changes in liver
- Mucositis (eg GI mucosa)
- Teratogenic
6
Q
5-Fluorouracil (5-FU) - MOA
A
- S phase specific
- Pyrimidine analog that is bioactivated to 5F-dUMP which covalently complexes folic acid –> Complex inhibits thymidylate synthase –> Inhibit production of dTMP –> Inhibit DNA and protein synthesis
7
Q
5-Fluorouracil (5-FU) - Clinical Use
A
- Colon cancer and other solid tumors
- Topical for basal cell carcinoma
- Synergistic with MTX
8
Q
5-Fluorouracil (5-FU) - Toxicities
A
- Myelosuppression which is not reversible with leucovorin (leucovorin actually increases the effects of 5-FU)
- The rescue for 5-FU overdose is Thymidine
- Photosensitivity
9
Q
6-Mercaptopurine (6-MP) - MOA
A
- S phase specific
- Same MOA as 6-TG
- Purine (thiol) analog bioactivated by HGPRTase (ie the enzyme that converts Hypoxanthine and Guanine to IMP and GMP in the purine salvage/degredation pathway) –> Inhibits purine synthesis
10
Q
6-Mercaptopurine (6-MP) - Clinical Use
A
- Leukemias
- Lymphomas
- Not for CLL or Hodgkin’s Lymphoma
11
Q
6-Mercaptopurine (6-MP) - Toxicities
A
- Bone marrow suppression
- GI mucosa
- Liver toxicity
- Metabolized by Xanthine oxidase (ie Another enzyme in the purine salvage/degredation pathway that degrades hypoxanthine and xanthine to xanthine and uric acid respectively) –> Increased toxicities when administered with Allopurinol (i.e. a Xanthine oxidase inhibitor)
12
Q
6-Thioguanine (6-TG) - MOA
A
- S phase specific
- Same MOA as 6-MP
- Purine (thiol) analog bioactivated by HGPRTase (ie the enzyme that converts Hypoxanthine and Guanine to IMP and GMP in the purine salvage/degredation pathway) –> Inhibits purine synthesis
13
Q
6-Thioguanine (6-TG) - Clinical Use
A
- Acute lymphoblastic (/lymphocytic, /lymphoid) leukemia (/lymphoma) - ALL
14
Q
6-Thioguanine (6-TG) - Toxicities
A
- Bone marrow depression
- Liver toxicity
- Can be given with Allopurinol (i.e. a Xanthine oxidase inhibitor)
15
Q
Cytarabine (ara-C) - MOA
A
- S phase specific
- Pyramidine analog inhibit DNA polymerase
16
Q
Cytarabine (ara-C) - Clinical Use
A
- AML
- ALL
- High grade non-Hodgkin’s lymphoma
17
Q
Cytarabine (ara-C) - Toxicities
A
- Leukopenia
- Thrombocytopenia
- Megaloblastic anemia
18
Q
Antitumor Antibiotics - Available Drugs
A
- Dactinomycin (Actinomycin D)
- Doxorubicin (Adriamycin) / Daunorubicin
- Bleomycin
- Etoposide (VP-16) / Teniposide
19
Q
Dactinomycin (Actinomycin D) - MOA
A
- No cell cycle specificity
- Intercalates in DNA
20
Q
Dactinomycin (Actinomycin D) - Clinical Use
A
Used for childhood tumors:
- Wilm’s tumor
- Ewing’s sarcoma
- Rhabdomyosarcoma
“Dactinomycin - Children act out”
21
Q
Dactinomycin (Actinomycin D) - Toxicities
A
- Myelosuppression
22
Q
Doxorubicin (Adriamycin) / Daunorubicin - MOA
A
- No cell cycle specificity
- Generate free radicals
- Non-covalently intercalate in DNA –> create DNA breaks –> decrease replication
23
Q
Doxorubicin (Adriamycin) / Daunorubicin - Clinical Use
A
- Hodgkin’s lymphomas
- Myelomas
- Sarcomas
- Solid tumors (breast, ovary, lung)
24
Q
Doxorubicin (Adriamycin) / Daunorubicin - Toxicities
A
- Dilated cardiomyopathy
- myelosuppression
- Alopecia
- Extravasation is toxic
- Dexrazoxane (i.e. an iron chelating agent) can be used to prevent the cardiotoxicity
25
**Bleomycin - MOA**
* G2 phase specific
* Induce free radical formation --\> DNA breaks
26
**Bleomycin - Clinical Use**
* Testicular cancer
* Hodgkin's lymphoma
27
**Bleomycin - Toxicities**
* Pulmonary fibrosis
* Skin changes
* Minimal myelosuppression
28
**Etoposide (VP-16) / Teniposide - MOA**
* S-G2 phase specific
* Inhibit topoisomerase II --\> DNA degredation
29
**Etoposide (VP-16) / Teniposide - Clinical Use**
* Small cell carcinoma of the lung and prostate
* Testicular carcinoma
30
**Etoposide (VP-16) / Teniposide - Toxicities**
* Myelosuppression
* GI irritation
* Alopecia
31
**Alkylating Agents - Available Drugs**
* Cyclophosphamide / Ifosfamide
* Nitrosoureas (Carmustine [BCNU], Lomustine [CCNU], Semustine [meCCNU], Streptozotocin[STZ])
* Busulfan
32
**Cyclophosphamide / Ifosfamide - MOA**
* No cell cycle specificity
* Nitrogen Mustards
* Same action as the Nitrosoureas and Alkyl Sulfonates
* Covalently X-link (interstrand) DNA at Guanine N-7
* Requires bioactivation in the liver
33
**Cyclophosphamide / Ifosfamide - Clinical Use**
* Non-Hodgkin's lymphoma
* Breast carcioma
* Ovarian carcinoma
* Also function as immunosuppressants
34
**Cyclophosphamide / Ifosfamide - Toxicities**
* Myelosuppression
* Hemorrhagic cystitis - can be partially prevented with administration of Mesna (i.e. thiol group of mesna binds toxic metabolites)
35
**Nitrosoureas - Available Drugs**
* Streptozocin (STZ)
* Carmustine (BCNU)
* Lomustine (CCNU)
* Semustine (meCCNU)
36
**Nitrosoureas - MOA**
* No cell cycle specificity
* Same action as the Nitrogen Mustards and Alkyl Sulfonates
* Covalently X-link (interstrand) DNA at Guanine N-7
* Requires bioactivation in the liver
* **Can cross the BBB --\> CNS**
[BCNU, CCNU, meCCNU, STZ]
37
**Nitrosoureas - Clinical Use**
* **Brain tumors, including Glioblastoma multiforme**
[BCNU, CCNU, meCCNU, STZ]
38
**Nitrosoureas - Toxicities**
CNS toxicities
* Dizziness
* Ataxia
[BCNU, CCNU, meCCNU, STZ]
39
**Busulfan - MOA**
* No cell cycle specificity
* An Alkyl Sulfonate
* Same action as the Nitrogen Mustards and Nitrosoureas
* Covalently X-link (interstrand) DNA at Guanine N-7
40
**Busulfan - Clinical Use**
* CML
* Also used to ablate patient's bone marrow prior to a bone marrow transplantation
41
**Busulfan - Toxicities**
* Pulmonary fibrosis
* Hyperpigmentation
42
**Cisplatin / Carboplatin - MOA**
* No cell cycle specificity
* Platinum crosslinking compounds
* Function very similarly to the alkylating agents but lack an alkyl group.
* Cross-link DNA
43
**Cisplatin / Carboplatin - Clinical Use**
* Testicular carcinoma
* Bladder carcinoma
* Ovarian carcinoma
* Lung carcinoma
44
**Cisplatin / Carboplatin - Toxicities**
* Nephrotoxicity
* Acoustic nerve damage
* Prevent nephrotoxicity with Amifostine (i.e. a free radical scavenger) and chloride diuresis
45
**Microtubule Inhibitors - Available Drugs**
* Vincristine / Vinblastine
* Taxols (e.g. Paclitaxel)
46
**Vincristine / Vinblastine - MOA**
* M phase specific
* Vinca Alkaloids
* Bind tubulin and block polymerization of microtubules so that the mitotic spindle cannot form
"Microtubules are the **vin**es of your cells"
47
**Vincristine / Vinblastine - Clinical Use**
* Hodgkin's lymphoma
* Wilm's tumor
* Choriocarcinoma
* ALL
48
**Vincristine / Vinblastine - Toxicities**
Neurotoxicity
* Areflexia
* Peripheral neuritis
* Paralytic ileus
**Bone marrow suppression**
"Vin**blast**ine **Blast**s **B**one marrow"
49
**Paclitaxel - MOA**
* M phase specific
* A Taxol
* Hyperstabilize polymerized microtubules so the mitotic spindle cannot break down --\> no progression to anaphase
"It is **tax**ing to stay polymerized
50
**Paclitaxel - Clinical Use**
* Ovarian carcinoma
* Breast carcinoma
51
**Paclitaxel - Toxicities**
* Myelosuppression
* Hypersensitivity
52
**Hydroxyurea - MOA**
* S phase specific
* Inhibits ribonucleotide reductase --\> Decreased DNA synthesis
53
**Hydroxyurea - Clinical Use**
* Melanoma
* CML
* Sickle cell disease (increased HbF)
54
**Hydroxyurea - Toxicities**
* Bone marrow suppression
* GI upset
55
**Prednisone - MOA**
May trigger apoptosis, may even work on non-dividing cells
56
**Prednisone - Clinical Use**
Most commonly used glucocorticoid in chrmotherapy
* CLL
* Hodgkin's lymphoma (part of MOPP regimen)
* Also an immunosuppressant used in autoimmune disease
57
**Prednisone - Toxicities**
* Cushing's like symptoms
* Immunosuppression
* Cataracts
* Acne
* Osteoperosis
* HTN
* Peptic ulcers
* Hyperglycemia
* Psychosis
58
**SERMs - Available Drugs**
* Tamoxifen
* Raloxifene
59
**SERMs - MOA**
Estrogen receptor antagonists in breast tissue
[Tamoxifen, Raloxifene]
60
**SERMs - Clinical Use**
* Breast cancer
* Also used in treatment of osteoperosis
[Tamoxifen, Raloxifene]
61
**SERMs - Toxicities**
Tamoxifen
* Increased risk of endometrial carcinoma due to agonistic effect at endometrium
* Hot flashes
Raloxifene
* No risk of endometrial carcinoma - antagonistic at the endometrium
62
**Trastuzumab (Herceptin) - MOA**
Monoclonal antibody against HER-2 (erb-B2) tyrosine kinase
* Helps mediate killing of HER-2 (+) breast cancer, possibly through antibody dependent cytotoxicity
"Tras-2-zumab"
63
**Trastuzumab (Herceptin) - Clinical Use**
Metastatic breast cancer
64
**Trastuzumab (Herceptin) - Toxicities**
* Cardiotoxicity
65
**Imatinib (Gleevec) - MOA**
Inhibitor of the bcr-abl tyrosine kinase (i.e. product of the Philadelphia chromosome)
66
**Imatinib (Gleevec) - Clinical Use**
* CML
* GI stromal tumors
67
**Imatinib (Gleevec) - Toxicities**
* Fluid retention
68
**Rituximab - MOA**
Antibody against CD20, which is found in most B cell neoplasms
69
**Rituximab - Clinical Use**
* Non-Hodgkin's lymphoma
* Rheumatoid arthritis (w/ methotrexate)
70
**Leucovorin - MOA**
Folinic acid
* Gets converted to THF without the need of dihydrofolate reductase
71
**Leucovorin - Clinical Use**
* Rescue to myelosuppression associated with MTX
* Enhance the effects of 5-FU
72
**Dexrazoxane - MOA**
Iron chelator --\> Reduce the number of iron particals complexed with Anthracyclines (e.g. Doxorubicin, Daunorubicin) --\> Lower free radical formation --\> Reduce oxidative damage
73
**Dexrazoxane - Clinical Use**
Help prevent the cardiotoxicity of the Anthracyclines (e.g. Doxorubicin, Daunorubicin)
74
**Mesna - MOA**
Thiol group on Mesna binds the toxic metabolites of Cyclophosphamide / Ifosphamide
75
**Mesna - Clinical Use**
Prevent the Hemorrhagic cystitis caused by Cyclophosphamide / Ifosphamide
76
**Amifostane - MOA**
Scavenges toxic metabolites and free radicals
77
**Amifostane - Clinical Use**
Help prevent the nephrotoxicity of the Platinum crosslinking compounds
