Anti-Tumor Agents Flashcards
Adjuvant-
after local treatment, trying to kill micrometastases
Neoadjuvant-
before localized treatment, trying to make that treatment more effective and less damaging
Primary-
on its own with no other therapy in a few cases curative, more often for palliation of symptoms in patients with advanced disease
Understand major differences between “targeted therapies” and conventional cytotoxics: conventional
Conventional agents damage normal cells as well as tumor cells- therapeutic window is largely based on tumor cells being closer to their apoptotic threshold, MTD relevant for conventional agents less so for targeted agents, which are usually less toxic, resistance mechanisms different. Remember: conventional cytotoxics hit specific targets (e.g. Topoisomerase/DNA) just like “targeted” agents do- difference is that with the newer “targeted” agents we aim to hit a target that is different/faulty in tumor cells but not normal cells.
Understand basis for combining anti-tumor agents.
Combine agents that work to at least some extent on their own, avoid overlapping toxicities, use drugs at optimal doses, keep treatment-free schedules as short as possible
Understand mechanism of action, major toxicities and resistance mechanisms of prototypical drugs for each class of anti-tumor agent.
DNA damaging agents, toposiomerase interacting agents, microtubule interacting agents, hormonal agents, antibodies, kinase inhibitors. Some resistance mechanisms generally applicable- e.g. drug efflux through transporters, some specific to agent- e.g. mutations in drug target, activation of repair mechanisms, other ways to activate steroid receptors. Many drugs have similar toxicities- usually associated with damage to fast growing cells- GI toxicity, myelosuppression. Specific toxicities depend upon mechanism of action- e.g. neurotoxicity associated with microtubule-interacting agents.
Understand major differences between “targeted therapies” and conventional cytotoxics: targeted
The new thing. Identifies specific genetic damage responsible for tumor, use drug that targets cells that contain
this particular defect.
• Sometimes hard to dose due to difficulty gauging response.
• Drugs chosen based not on the tumor site or histology, but on the underlying defects.
• Obviously, the $64,000 question is how to determine how a particular person’s tumor has come about.
• Notice that cytotoxic agents do ‘target’ specific pathways in cells; it’s just that they target those pathways in all cells. Targeted
therapies try to aim at damaged cells only.
Mechanisms for chemotherapy drugs
DNA damaging agents, toposiomerase interacting agents, microtubule interacting agents, hormonal agents, antibodies, kinase inhibitors.
cyclophosphamide (mechanism and toxicity)
DNA damage - alkylating agent (covalent chemical adducts)
-toxicities: heme, GI, gonadal, alopecia
Methotrexate (mechanism and toxicity)
Antimetabolite - competitive inhibitor of DHFR
-tox: myelosupp, GI, renal, hepato, neuro, tetrogeneticity
5-Fluorouracil (mechanism and toxicity)
Anti-metabolite - pyrimidine analog (FdUMP)
-tox: myelosupp, GI, alopecia
Topoisomerase (mechanism and toxicity)
- topoisomerase 0 single of double strand breaks by stablizing complex between topoisomerse and DNA
- tox: myelo, cardio, 2ndary malignancies (i.e. AML)
Vinca alkaloids (mechanism and toxicity)
anti-MT agents - stabilize and depolymerize -> breakdown of MTs
-tox: neuro, myelo, neutrophil
Taxane (mechanism and toxicity)
anti-MT agent - stabilize against MT depolarization by binding to internal surface
-tox: myelo (neutrophil), neuro, alopecia
Rituximab
AB chemo drug
B cell tumors
