CHEMOTHERAPY OF NEOPLASTIC DISEASES 3 Flashcards
Who are the vinca alkaloids and what do they do
Vincristine
Vinblastine
- Destabilizing agents.
- Vinca alkaloids bind to β-tubulin and inhibit its ability to polymerize into microtubules.
- This results in mitotic arrest in metaphase.
- Cell division stops. Cells die by apoptosis.
Adverse effects of vincristine
- Peripheral neuropathy.*****
- Bone marrow depression is mild.
- Alopecia.
Adverse effects of vinblastine
• Myelosuppression is the dose-limiting
adverse effect.*****
• Peripheral neuropathy
• Alopecia
Example of a taxane and its MOA
Paclitaxel
- Stabilizing agent.
- Taxanes bind to the β-tubulin subunit of microtubules and promote microtubule polymerization.
- Stabilization of the microtubules in a polymerized state arrests cells in mitosis and leads to apoptosis.
TAXANES: ADVERSE EFFECTS
• Hypersensitivity, myelosuppression, peripheral neuropathy, alopecia.
How to reduce hypersensitivity from taxane
by premedication with dexamethasone, diphenhydramine and an H2 blocker
EPIPODOPHYLLOTOXINS:
ETOPOSIDE MOA
Inhibits topoisomerase II, resulting in DNA damage through strand breakage.
Blocks cell in late S-G2 phase
What are the adverse effects of etoposide
- Nausea, vomiting, alopecia.
* Myelosuppression.
Which drugs are camptothecins and what is their MOA
TOPOTECAN
IRINOTECAN
Inhibit topoisomerase I. Inhibition results in DNA damage.
Adverse effects of camptothecins
Myelosuppression and diarrhea
Which glucocorticoid is used and what is it used for
PREDNISONE
• Glucocorticoids are lympholytic and suppress mitosis in lymphocytes.
• They are used for acute leukemia and malignant lymphomas.
Who are the estrogen inhibitors
- SELECTIVE ESTROGEN-RECEPTOR MODULATORS (SERMs)
- ESTROGEN-RECEPTOR ANTAGONISTS
- AROMATASE INHIBITORS (AIs)
Who are your SERMS AND what do they do
TAMOXIFEN
RALOXIFENE
• SERMs bind to estrogen receptors and act as agonists or antagonists depending on the tissue.
What is tamoxifen used for
- Metastatic breast cancer in women and men.
* Preventive agent in women at risk for breast cancer.
- Tamoxifen is an ____________ on breast tissue.
* Tamoxifen is an ____________ in nonbreast tissues.
- Tamoxifen is an antagonist on breast tissue.
* Tamoxifen is an agonist in nonbreast tissues.
ADVERSE EFFECTS of tamoxifen
- Hot flashes. Nausea. Vomiting. Fluid retention.
- Vaginal bleeding.
- Venous thromboembolism.
- Increases incidence of endometrial cancer**
Tamoxifen is metabolized by CYP2D6 so it needs to stay away from Strong inhibitors of CYP2D6. Or else there would be accumulation . Who are Strong Inhibitors of CYP2D6?
Bupropion Fluoxetine Paroxetine
What is raloxifene used for ?
- Prophylaxis of breast cancer in high-risk postmenopausal women. (Anti estrogen effect)
- Treatment and prevention of osteoporosis in postmenopausal women. (Estrogenic effect)
Adverse effects of raloxefine
- Hot flashes.
- Leg cramps.
- Venous thromboembolism.
Who is the estrogen antagonist
FULVESTRANT
• Fulvestrant is devoid of estrogen agonist activity.
• Fulvestrant binds to the estrogen receptor (ER) inhibits its dimerization and increases its degradation.
• ER-mediated transcription is abolished.
Which drug is the Treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.
FULVESTRANT
• Aromatase converts ______ to estrone.
• Aromatase converts androstenedione to estrone.
Uses of aromatase inhibitors
the standard of care for adjuvant treatment of postmenopausal women with hormone receptor–positive breast cancer.
Who are the non steroidal aromatase inhibitors
ANASTROZOLE & LETROZOLE
• Nonsteroidal.
• Reversible competitive inhibitors of aromatase.
Who are the steroidal aromatase inhibitors
Steroidal
Inverse inhibitor of aromatase
Who are the GONADOTROPIN-RELEASING HORMONE AGONISTS
GOSERELIN
LEUPROLIDE
Synthetic analogs of gonadotropin-releasing hormone.
• When given continuously or as a depot preparation, they cause an initial surge in LH and FSH levels, resulting in a transient increase in circulating gonadal steroids, followed by inhibition of gonadotropin release.
This results in reversible suppression of ovarian and testicular steroidogenesis.
- Testosterone levels fall to 10% of their initial values after a month with GnRH analogs.
- But they increase in the beginning, causing a transient flare of tumor activity and an increase in symptoms.
- The flare phenomenon can be counteracted with?
Flutamide
GONADOTROPIN-RELEASING HORMONE AGONISTS USES:
- Advanced carcinoma of the prostate. Alone or in combination with flutamide.
- Advanced breast cancer in premenopausal women.
- Management of endometriosis.
Flutamide MOA
- Synthetic, nonsteroidal antiandrogen.
- Metabolized to an active metabolite that acts as a competitive antagonist at the androgen receptor, preventing its translocation to the nucleus.
MOA of gefitinib and erlotinib
Inhibitors of the EGFR tyrosine kinase.
What does lapatinib do
Inhibitor of EGFR and Her2 tyrosine kinases.
Which drug is an Inhibitor of the tyrosine kinase of Bcr-Abl?
Imatinib
Used for Ph+ Chronic Myeloid Leukemia Ph+ Acute Lymphoblastic Leukemia
Myelodysplastic/ Myeloproliferative Diseases
Who is the first line drug for Breast cancer with HER2 over-expression and what does it do
Trastuzumab - Monoclonal antibody against Her2.
Which drug is used for the following
Metastatic colorectal cancer
Non-small cell lung cancer
Glioblastoma multiforme
Renal cell carcinoma
Bevacizumab- monoclonal antibody against VEGF
ASPARAGINASE MOA
Asparaginase hydrolyzes serum asparagine, depriving these cells of the asparagine necessary for protein synthesis, leading to cell death.
ASPARAGINASE: ADVERSE EFFECTS
- Hypersensitivity.
- Decrease in clotting factors.
- Liver abnormalities.
- Pancreatitis, seizures, coma due to ammonia toxicity.
Which drug inhibits ribonucleotide reductase leading to depletion of deoxynucleoside
trisphosphate pools?
Hydroxyurea
It inhibits dna synthesis and kills cells in S phase .
Which drug is Approved for hairy cell leukemia, chronic myelogenous leukemia (CML), malignant melanoma and Kaposi’s sarcoma.
Interferon alpha
DOC for brain cancer
Lomustine, Carmustine
DOC for Breast:
Hormone receptor-positive
Aromatase inhibitor
Tamoxifen
Fulvestrant
GnRH agonists
Breast:
Tumors overexpressing HER2
Trastuzumab
Doc for prostate cancer
GnRH agonist ± flutamide
Cisplatin is the DOC for which three cancers
Ovarian
Testicular
Lung
DOC for colorectal cancer
Fluorouracil + leucovorin
