Pharmacology- Hematologic Malignancies II Flashcards
What should you do through out treatment for pts. who are receiving tx for cancer?
support due to myelocuppression and immunosuppression
What governs the design of txments regimens?
Toxicity of “Classical” anit-cancers
What are the governing principles that guide the combination therapies?
- dug MUST show activity against tumor type
- No two drugs should have the same mechanism of action
- Drugs should have different patterns of does-limiting toxicity
What are the stages of chemo?
Induction
Consolidation
Maintenance
What is induction?
high dose cobination chemo
What is consolidation?
repetition of induction therapy during remission
what is maintenance?
long term lower does therapy during remission
What is Neo-adjuvant?
before or during surgery/ radiotherapy
What is adjuvant?
given after surgery/ radiotherapy
What is metronomic dosing?
- giving a lower does everyday, versus high dose every few days or wks.
- showing positive date against many types of cancer but not all tumor types/. pts respond
What is hormesis?
txments designed to kill tumor cells or suppress their proliferation in pts. may have the capacity to enhance tumor growth when the drug is present in certain concentraitons
What may metronomic dosing avoid?
the pro-proliferatice aspect of drug response
Explain metronomic chemotherapy.
exerts both direct and indirect effectos on tumor cells and their microenviorment.
- it can inhibit tumor angiogenesis, stimulate anticancer immune response and may also be able to directly affect tumor cells through a therorectical drug-driven dependency/ deprivation effect,
- the direct effects of metronomic chemo on the differnt compartments of hte tumor micorenviorment and the complex interaction b/n these compartment may lead to additional anticancer effects and potential induction of tumor dormancy
What is an adaptive or evasive resistance?
the ability of a tumor, after an initaila response phase, to adapt so as to evade the therapeutic blockade by inducing or accentuating mechanisms that enable enovascularization despite the therapeutic dlockade, or educe dependence on such growth of new blood vessesls by other means, leading to renewed tumor growth and progression
What is adaptive therapy and why has it come about?
This innovative type of cancer treatment, which can be regarded as a gradually decreasing metronomic chemotherapy regimen, takes into account the complex interactions between resistant and non-resistant cancer clones. Adaptive therapy aims to maintain the equilibrium between these two populations to preserve a certain level of tumor sensitivity to treatment and induce lifetime-long control, rather than complete eradication, of the disease.
What effect does the immune response have on cancer control and how is it being changed by drug therapy to control cancer?
- adaptive immune system has a key role in the development and the control of cancer.
- In addition to the well-characterized adverse effects of chemotherapy on the immune system, such as neutropenia and lymphopenia, various studies suggest that certain cytotoxic drugs, such as anthracyclines, taxanes and cyclophosphamide, display important immunostimulatory properties, amongst which, their effect on regulatory t cells (treG) seem to be quite relevant in the context of metronomic treatments.
- Experimental studies have shown that low doses of cyclophosphamide can increase anti-tumor immune response by selectively decreasing numbers and inhibiting the suppressive functions of treG cells but also by increasing both lymphocyte proliferation and memory t cells. Metronomic cyclophosphamide reduces both the frequency of circulating treG cells and their immunosuppressive functions in advanced cancer patients. nK cell cytotoxic activity and t-cell-receptor induced t cell proliferation were subsequently restored in these patients.
- Some chemotherapeutic drugs—including vinblastine, paclitaxel and etoposide that can be used in metronomic chemotherapy regimens—promote infiltration and maturation of dendritic cells at non-toxic concentrations, thus stimulating anti-tumor immune response.
What are some side effects of metronomic dosing?
-grade 1 nausea and vomiting
-grade 1 and grade 2 anemia
neutropenia, leucopenia and lymphopenia
-associations with secondary diseases *leukemias)
What are the classifications of leukemias?
acute (short natural history)
choronic (long natural history)
Myeloid or lymphoid origin
->1/5– ALL, AML with remainder CLL and CML
What leukemias is seen mostly in childhood?
ALL
What leukmia is seen mostly in elderly?
CLL
What are the drugs approved for acute myeloid leukemia? (AML)
cyclophosphamide Cytarabine, ARA-C Daunorubicin Doxorubicin Idarubicin Gemtuzumab Mitoaxantrone Thioguanine, 6-TG
What is the most effective txment for AML?
a two-drug regime of daunorubicin and cytarabine – 65% response rate
-given with thioguanine, 6-TG is better is able to be done
What is the mechanism of Gemtuzomab?
- recombiant humanized CD33 monoclonacl antibody
- It carries calicheamicin, an antitumor antibiotic that cleaves dsDNA at specific sequences
What is post-remission therapy?
a short-term, relatively intensive chemo
- uses cytratbine-based regimens similar to standard induction clinical trials
- can also do a high-does chemotherapy or chemoradiation therapy with autologous bone marrow resuce (if HLA-identified sib is identified), and high-does marrow-ablative therapy with allogeneic bone marrow rescue
