What are the non-cell cycle specific cancer drugs?
- Alkyalting agents (cyclophosphamide, cisplatin, and procarbazine)
- Antitumor Abx (doxorubicin, daunorubicin)
- Nitrosureas (lomustine, carmustine)
What are the S phase specific cancer drugs?
- Hydroxyurea
- Methotrexate
- Irinotecan
- Cytarabine
- Etoposide
- 6-mercaptopurine
- 6-thioguanine
- 5-fluorouracil
What is the G2 phase specific cancer drug?
Bleomycin
What are the M phase specific cancer drugs?
- Vinblastine
- Vincristine
- Paclitaxel
What is the specific MOA of cyclophosphamide?
-Alkylating agent-attacks guanine N7-dysfunctional DNA
What are the side effects of cyclophosphamide?
- Bone marrow suppression
- Hemorrhagic cystitis
What is used to treat the hemorrhagic cystitis caused by cyclophosphamide and what is its MOA?
Mesna-traps acrolein and is protective
What is the specific MOA of doxorubicin?
- Intercalator -> forms free radicals
- Inhibits topoisomerase
What are the side effects of doxorubicin?
- Bone marrow suppression
- Delayed CHF (heart damage is caused by the free radicals)
What is used to prevent the free radicals formed by doxorubicin?
Dexrazoxane-iron chelating agent that prevents the formation of free radicals
What is the specific MOA of methotrexate?
-Antimetabolite-inhibits DHF reductase (S phase)
What is the main side effect of methotrexate?
Bone marrow suppression
What is used to prevent the toxicity of methotrexate?
Leucovorin (folinic acid) rescue
What is the specific MOA of 5-fluorouracil/capecitabine (oral form)?
Pyrimidine antimetabolite (S phase) bioactivated to inhibit thymidylate synthetase
What is the specific MOA of bleomycin?
Complexes with Fe and oxygen -> DNA strand scission (G2 phase)
What are the main side effects of bleomycin?
Pulmonary fibrosis and pneumonitis
What is the specific MOA of vincristine/vinblastine?
Inhibition of microtubular polymerization - spindle poisons (M phase)
What is the main side effect of vincristine?
Neurotoxicity
What is the specific MOA of all-trans retinoic acid?
-Differentiating agent, promotes differentiation of promyelocytes
All-trans retinoic acid is used to treat what specific cancer?
Acute myelogenous leukemia (AML), M3
What are the main side effects of all-trans retinoic acid?
“Differentiation syndrome”-with respiratory distress, pleural and pericardial effusions, CNS symptoms
Explain the what causes the “thymineless death of fungal cells and neoplastic cells” and which agents are used for each
Flucytosine (FC) and 5-fluorouracil (5-FU) are bioactivated to 5-FdUMP which inhibits thymidylate synthetase -> thymineless death
- FC is used for fungal cells
- 5-FU is used for neoplastic cells
What is the specific MOA of paclitaxel?
Blocks depolymerization of microtubules
What is the specific MOA of irinotecan?
Blocks topoisomerase 1
What is the specific MOA of etoposide?
Blocks topoisomerase 2
What is the target of imatinib?
BCR-ABL
Imatinib is used in the treatment of what specific cancer?
CML
What is the target of cetuximab?
ErbB1
Cetuximab is used in the treatment of what specific cancers?
Cancers of the head, neck, and colon
What is the target of trastuzumab?
ErbB2 (HER2/neu) (EGFR inhibitor)
Trastuzumab is used in treatment of what specific cancer?
Breast cancer
What is the target of bevacizumab?
VEGF-A
What is the target of sorafenib?
RAF kinase
Cisplatin is associated with toxicity of what organ?
Renal (nephrotoxicity)
Bleomycin is associated with toxicity of what organ?
Pulmonary
Doxorubicin is associated with toxicity of what organ?
Cardiac
Vincristine is associated with toxicity of what organ?
Neurologic
Cyclophosphamide is associated with toxicity of what organ?
Bladder (hemorrhagic cystitis)
Name the bone marrow “sparing” cancer drugs
- Vincristine
- Cisplatin
- Asparaginase
- Bleomycin
What type of cancer drugs are more effective against tumors with high growth fractions (leukemias/lymphomas)?
Cell cycle specific drugs
Non-cell cycle specific drugs are effective against?
Tumors with high or low growth fractions
What is the antidote used to prevent the nephrotoxicity caused by cisplatin?
Amifostine
What is aldesleukin?
- IL-2
- Increases lymphocyte differentiation and NKs
What does IL-11 do?
Increases platelet formation
What is filgrastim?
- G-CSF
- Increases granulocytes
What is sargramostim?
- GM-CSF
- Increases granulocytes and macrophages
What is the log-kill hypothesis?
The cytotoxic actions of anticancer drugs follow first order kinetics - kill a fixed PERCENTAGE of cancer cells