Antimitotic and Biological response modifiers - Slides 1-23 Flashcards
How do Antimitotic drugs work?
They either interfere with the mitotic process by altering spindle formation or degradation (M phase specific)
OR
Inhibition of the topoisomerase I or II enzyme, which is S-G2 phase specific.
Topoisomerase I breaks and reseals single stranded DNA
Topoisomerase II does the same on double stranded DNA
Vinca’s block ________; Taxane’s block _______
Vinca’s block assembly
Taxane’s block disassembly
How are Vinca alkaloids administered?
IV (does not enter CNS)
Vinorelbine has oral activity
What is Vincristine used for?
Lymphomas ALL Hodgkin's Part of MOPP's Neuroblastoma Wilm's tumor Sarcoma's
What is Vinblastine used for?
Testicular tumors Hodgkin's Breast Part of ABVD therapy Non-hodgkin's lymphoma
What is Vinorelbine used for?
Breast
Non-small cell lung cancer (esp elderly)
Toxicities for Vinca agents?
Common to all agents:
Rapid cytotoxic effects and cell destruction
Leads to hyperuricemia due to oxidation of purines to uric acid
(Give allopurinol to help prevent buildup)
Strong vesicants - if out of the vein, use heat or hyaluronidase to disperse the drug
What is Hyalouronidase?
Used to disperse the Vinca agents if they escape the vein to prevent tissue damage
Vincristine toxicities?
Dose limiting neurotoxicity
Peripheral neuropathies of hands and feet
May affect both sensory and motor nerves
Suppression of deep tendon reflexes
Cranial nerve damage
May cause jaw damage, face palsies
Muscle weakness, autonomic neuropathies, constipation
MINIMAL MYELOSUPPRESSION
Vinblastine toxicities?
Dose limiting myelosuppression
Mild neurotoxicity
N/V/D, stomatitis
Vinorelbine toxicities?
Myelosuppression
N/V/D
Least neurotoxicity of the vinca’s!
How do Paclitaxel, Docetaxel work?
They cause cell division to stop in M phase, causes aptoptosis
Indications for Paclitaxel, Docetaxel?
Metastatic ovarian, breast, lung, GI, bladder, head and neck, esophageal, prostate
Name the taxanes
Paclitaxel
Docetaxel
Cabazitaxel
Name the vinca’s
Vincristine
Vinblastine
Vinorelbine
Toxicities with paclitaxel?
Myelosuppression Hypersensitivity reactions due to diluent Give H1/H2 and dexamethasone Stocking-glove sensory neuropathy Myalgia
Toxicities with Docetaxel?
Neutropenia
Less severe peripheral neuropathy
Less hypersensitivit reactions
Fluid retention and edema, start dexamethasone 1 day prior
Which drugs require dexamethasone pretreatment? Why?
Paclitaxel - bc of hypersensitivity rnxns
Docetaxel - bc of fluid retention and edema
Indications for Cabazitaxel?
Metastatic hormone resistant prostate cancer
Increases survival 3 months over standard therapy but is very expensive - weigh risk/benefits
Toxicities with Cabazitaxel?
Neutropenia Anemia Diarrhea Fatigue Nausea Vomiting Alopecia Peripheral neuropathy
What are Epothilones? What is the only agent available?
A new class of microtubule damaging compounds isolated from myxobacterium on Zambezi river in South Africa
Ixabepilone was FDA approved in 2007
What is Ixabepilone used for?
Metastatic breast cancer after other treatments
How is Ixapebilone administered?
IV
What is the MOA of Ixabepilone?
Inhibits tubulin breakdown like taxanes but binds to a different site
Toxicities of Ixabepilone?
Neutropenia
Peripheral sensory neuropathy
Fatigue
Diarrhea
What are Epiodophyllotoxins?
Etoposide
Teniposide
They inhibit Topoisomerase II, causing strand breaks
Specific for S-G2
How is Etopisode administered?
Oral and IV
What is the difference in metabolism between Etoposide and Teniposide?
40% of Etoposide is excreted unchanged in the urine
Teniposide is extensively metabolized
What is Etoposide used for?
Testicular, lung, non-Hodgkin’s lymphoma, breast, AML
How is Teniposide administered?
IV
What is Teniposide used for?
Acute lymphocytic leukemia in children
Neuroblastoma
Toxicities for Etoposide AND Teniposide?
Both: Alopecia N/V Dose limiting myelosuppression!!!! Stomatitis
Etoposide toxicities
Unusual non-lymphocytic leukemia due to alteration on chromosome 11, can occur 1-3 years after therapy for ALL in children treated with HIGH doses
Gene is MLL - mixed lineage leukemia gene, regulates proliferation of stem cells
What are Irinotecan, Topotecan?
Camptothecins isolated from the Chinese happy tree
They inhibit topoisomerase I causing single strand breaks in DNA
Irinotecan metabolism?
It’s a prodrug, metabolized and excreted in the bile
Topotecan metabolism?
IV, Renal excretion
Indications for Irinotecan?
Colorectal, breast, cervical, gastric, lung
Indications for Topotecan?
Lung, ovarian
Toxicities for Irinotecan, Topotecan?
Dose limiting myelosuppression (BOTH)
Diarrhea (Irinotecan more than Topotecan, give Loperamide)
Nausea, vomiting
Alopecia
Decreased cholinesterase activity (Irinotecan)
