Chemo, Antineoplastics, Alkylating Agents + Platinum complex

Which of the following disease are cytotoxic drugs the primary curative modalitlies?

• Leukemias

• Lymphomas

• choriocarcinomas

• testicular cancer

Which of the following are true about Cytotoxic actions of alkylating agents?

• Cell cycle non-specific

• interferes w/ DNA integrity and function to induce apoptosis in rapidly proliferating tissues.

• Specific to the M phase of the cell cycle

• Malignant cells with mutant or absent p53 can exhibit resistance to these drugs

Which of the following determines the lethality of DNA alkylation?

• The recognition of the adduct

• The creation of DNA strand breaks by repair enzymes

• An intact apoptotic response

• A mutated apoptotic response

Match the following

• Monofunctional methylating agents

• Cross-link

• Alkylating agents react with an atom on both strands of DNA

• Bifunctional

• A covalent link between the two strands of the DNA double helix

• Monofunctional

• Bifunctional Agents

• Cytotoxic effects predominate

• alkylating agents react with only one strand of DNA

• Greater capacity for mutagenesis and carcinogenesis

Which of the following is true about Alkylating drugs?

• Form highly reactive carbonium ion intermediates

• Their chemotherapeutic and cytotoxic effects are not due to alkylation

• Form carbonium ion intermediates that have no reactivity

• They are not used in cancer treatment

Match the following drugs to the cancer that they treat

• non-Hodgkins lymphomas, breast+ovarian cancer, solid tumors in kids. cure for Burkitt Lymphoma

• Mechlorethamine (Chlormethine)

• Relapsed germ cell testicular cancer

  pediatric or adult patients w/ sarcomas

• Melphalan

• multiple myeloma

• Chlorambucil

• Chronic Lymphocytic Leukemia

  Can be used for months/years w/o significant toxicity

• Cyclophosphamide

• Topical: Cutaneous T-cell Lymphoma

  Part of MOPP regimen for Hodgkin Lymphoma

• Ifosfamide

Which of the following are true about cyclophosphamide?

• Phosphoramide mustard is responsible for antitumor effects

• Acrolein causes hemorrhagic cystitis often seen during therapy with cyclophosphamide

• Can be used in patients with renal dysfunction bcuz its eliminated by the liver

• Cannot be used in patients w/ renal dysfunction bcuz its eliminated by the kidneys.

What drug am I? Prodrug

Mono-functional methylating agent

kills cells in all phases of the cell cycle

MGMT can cause drug resistance

IV administration

Used for Hodgkin's disease primarily. Modestly effective against malignant melanoma

• Dacarbazine (DTC)

• Temozolomide

• cisplatin

• Carmustine

Which of the followng are true about the mechanisms of resistance to alkylating drugs?

• Resistance develops rapidly when its used as a single agent

• Decreased permeation of actively transported drugs

• Increased intracellular concentrations of nucleophilic substances

• Increase activity of DNA repair pathways

• High expression of MGMT protecting cells from cytotoxic effects

Match the following mechanisms of resistance to Alkylating drugs to their descriptions

• into inactive keto and carboxy metabolites by aldehyde dehydrogenase

• Impaired apoptotic pathways

• overexpression of Bcl-2

• Loss of ability to recognize adducts formed by nitrosoureas and methylating agents.

• resulting from a defective mismatch repair protein capability.

• Increased rates of metabolic degradatin of the activated form of Cyclophosphamide + Ifosfamide