Chemotherapy Of Neoplastic Diseases 1 Flashcards
Primary chemotherapy
Chemotherapy indicated when neoplasms are disseminated and not amenable to surgery.
Adjuvant chemotherapy
Chemotherapy used to attack micrometastases following surgery and radiation.
Neoadjuvant chemotherapy
Chemotherapy given prior to surgery to shrink the cancer.
Log kill
a given dose of drug destroys a constant fraction of cells.
• A 1-log kill reduces the number of cancer cells by ___ %.
• A 2-log kill by ___ %.
• A 3-log kill by ___ %
A 5 log kill by___ %
• A 1-log kill reduces the number of cancer cells by 90 %.
• A 2-log kill by 99 %.
• A 3-log kill by 99.9 %
5 log kill 99.999%. However, there would still be 0.0001% of 10^6 cells (10^4 tumor cells) remaining in the body.
_____________are more sensitive to anticancer drugs, whereas nonproliferating cells usually survive their effects.
Rapidly dividing cells are more sensitive to anticancer drugs, whereas nonproliferating cells usually survive their effects.
Cell cycle-specific drugs
Exert their action on cells traversing the cell cycle.
Cell cycle-nonspecific drugs
can kill tumor cells whether they are cycling or resting in the G0 compartment.
CELL CYCLE-SPECIFIC AGENTS examples
Antimetabolites Bleomycin Microtubule inhibitors Epipodophyllotoxins Camptothecins
Remember BEAMC
Cell cycle non specific examples
APA
Alkylating agents
Platinum coordination complexes
Antitumor Antibiotics
Primary vs acquired resistance
PRIMARY RESISTANCE
• No response to the drug on the first
exposure.
ACQUIRED RESISTANCE • Single drug resistance - Due to increased expression of one or more genes. • Multidrug resistance (MDR) - Resistance emerges to several different drugs after exposure to a single agent.
Multi drug resistance is mainly due to membrane effluent pumps. Which effluent pump is most responsible
P-glycoprotein
Common adverse effects of toxicity
Remember BATSS
- Severe vomiting
- Stomatitis
- Bone marrow suppression
- Alopecia
- tumor lysis syndrome
Manifestations seen in tumor lysis syndrome
- Hyperuricemia
- Hyperkalemia
- Hyperphosphatemia
- Hypocalcemia (due to precipitation of calcium phosphate).
- Uric acid and calcium phosphate crystals may precipitate in the kidney and lead to renal failure.
How to manage tumor lysis syndrome
IV hydration with normal saline and allopurinol
or rasburicase.
Relative myelosuppression correlation to drugs
COMMON ADVERSE EFFECTS: EMETOGENIC POTENTIAL
Adverse effect of Doxorubicin & Daunorubicin
Cardio toxicity
Adverse effect of Cyclophosphamide & Ifosfamide
Hemorrhagic cystitis
Adverse effect of Cisplatin
Nephrotoxicity, Ototoxicity & Peripheral neuropathy
Adverse effect of Bleomycin & Busulfan
Pulmonary fibrosis
Adverse effects of Vincristine & Paclitaxel
Peripheral neuropathy
Adverse effect of Asparaginase
Hypersensitivity
Which drugs Reduce chemotherapy-induced nausea and vomiting (CINV)
5-HT3, NK-1 antagonists & dexamethasone
Which drug Rescues bone marrow from methotrexate.
Leucovorin
Which drug Reduces hemorrhagic cystitis caused by cyclophosphamide & ifosfamide.
Mesna
Which drug Reduces anthracycline-induced cardiotoxicity.
Dexrazoxane
Which drug reverses neutropenia
Filgrastim and sargramostin
Which drug reduces anemia
Erythropoietin
Which drug reverses thrombocytopenia
IL-11
Which drug Reduces renal toxicity caused by cisplatin.
Amifostine
Which drug prevents hyperuricemia of tumor lysis syndrome
Allopurinol or rasburicase
Example of a 5-HT3 antagonist for CINV
Ondansetron
NK-1 antagonist for CINV
Aprepitant
Corticosteroid for CINV
Dexamethasone
Adjunct therapy for CINV.
Benzodiazepines (Lorazepam or alprazolam)
Treatment-induced neoplasms are especially a problem after therapy with _______________
Treatment-induced neoplasms are especially a problem after therapy with alkylating agents.
Anti metabolite is an anti cancer drug. List the categories
FOLATE ANALOGS- methotrexate
PURINE ANALOGS
PYRIMIDINE ANALOGS
MOA of antimetabolites
- Antimetabolites target pathways related to nucleotide and nucleic acid synthesis.
- They are cycle-specific.
- Maximal cytotoxic effects are in the S-phase.
Methotrexate is: - structurally related to \_\_\_\_\_\_\_ • Inhibits\_\_\_\_\_\_\_\_\_\_\_\_ • The cell is deprived of folate • The synthesis of \_\_\_\_\_\_\_\_\_\_\_\_ decrease; consequently, synthesis of DNA, RNA, and protein decreases—>cell death.
Methotrexate is: - structurally related to folate • Inhibits dihydrofolate reductase • The cell is deprived of folate • The synthesis of dTMP and purine nucleotides decrease; consequently, synthesis of DNA, RNA, and protein decreases—>cell death.
Which enzyme catalyzes the conversion of methotrexate to polyglutamates
folylpolyglutamate synthase (FPGS).
• PGs are strongly charged and cross cellular membranes poorly: polyglutamation serves as a mechanism of ion trapping within the cell.
METHOTREXATE: ADVERSE EFFECTS
- Common: Stomatitis, mucositis, myelosuppression, alopecia, nausea, vomiting.
- Renal Damage: Uncommon. Complication of high-dose methotrexate.
- Hepatic fibrosis and cirrhosis.
- Pneumonitis.
- Neurologic Toxicities. With IT administration.
_________ provides the normal tissues with the reduced folate, thus circumventing the inhibition of DHFR.
Leucovorin (N5-formyl- THF) provides the normal tissues with the reduced folate, thus circumventing the inhibition of DHFR.
• Antidote to drugs that decrease levels of folic acid, such as methotrexate, to rescue the bone marrow.
