Cancer Chemotherapy Flashcards
What is the most common malignancy in the pediatric population?
Leukemia (Acute Lymphocytic leukemia)
Type of chemotherapy used for systemic cancers:
Induction chemotherapy
Type of chemotherapy used for localized cancers:
Neoadjuvant chemotherapy
Chemotherapy used as part of a combination of treatment modalities:
Adjuvant chemotherapy
The therapeutic goals of chemotherapy:
Cure some malignancies
Decrease the rate of relapse
Palliate symptoms
Reduce the size and extent of the primary tumor
These are anti-cancer drugs that act on one or several phases of the cell cycle; as such they are ____.
Cell Cycle Specific Drugs (CCS); schedule dependent drugs
Cell cycle nonspecific drugs act ____ the cell cycle; as such they are____.
inside and outside; dose dependent drugs
Most CCNS drugs are ____ and antibiotics (except for ___)
Alkylating agents; Bleomycin
Cancers with high growth fractions are?
Leukemia
Lymphoma
Cancers with low growth fractions are?
Solid tumors:
Ovarian CA
Colon CA
Lung CA
Cancer cell growth plateaus due to:
Depletion of nutrients (main cause)
Increase in competition
Confinement
The cardinal rule of chemotherapy:
There is an invariable inverse relation between cancerous cell numbers and curability
What are some factors affecting cell kill?
Dose intensity Schedule Drug Resistance Tumor site Patient's health status
What is the single drug used to treat choriocarcinoma?
Methotrexate
What is the single drug used Burkitt’s lymphoma?
Cyclophosphamide
ECV drug regimen hlung cancer?
Etoposide
Cisplatin
Vincristine
CMF drug regiment for breast cancer?
Cyclophosphamide
Methotrexate
Fluorouracil
Drugs that do NOT cause myelosuppression?
Hormones Streptozocin Vincristine Bleomycin Asparaginase Cisplatin
Serotonin antagonists used to treat N&V caused by CA treatment?
Ondansetron
Granisetron
What is the most common mechanism in multi-drug resistance?
P-glycoprotein mediated efflux of drug from cell
Anti-metabolic chemotherapy drugs?
Folic Acid analogs - Methotrexate
Purine analogs - Mercaptopurine
Pyrmidine Analogs - Flurouracil, Cytarabine
Source of reduced folates for treating MTX toxic effects?
Leucovorin + Folinic Acid
Uses of Methotrexate?
Acute Leukocytic Leukemia (ALL) Choriocarcinoma Non-Hodgkins Lymphoma Psoriasis GVHD
Mercaptopurine is converted to a T-IMP by HGPRT and then replaces what nucleotide purine?
Guanine
Similar to 6-MP but is not metabolized by xanthine oxidase and can be given with allopurinol:
Thioguanine
5-FU is converted to ___, which binds___, causing “___”.
FdUMP; thymidylate synthetase; thymineless death
Uses of 6-MP?
ALL
AML
CML
Uses of Flourouracil?
Adenocarcinoma
Severe psoriasis
Basal cell CA
Colorectal CA
Hand foot syndrome is associated with which pyrmidine analog?
Flourouracil
Cytarabine is used only in which malignancies?
NOT in solid tumors
Hematologic Malignancies:
AML (single most effective agent)
non-Hodgkins Lymphoma
ALL
Which phase of the cell cycle is most susceptible to alkylation?
G1 and S phase
Alkylation may result in:
DNA fragmentation
Mispairing
Cross linking
The major site of DNA alkylation is what?
N7 position of guanine - 2 alkyl groups must alkylate 2 guanine groups
Advantages of Cyclophosphamide (alkylating agent):
Favorable therapeutic index
Broadest spectrum of activity
High bioavailability
Antidote to cyclophosphamide?
MESNA+
This is the slowest acting nitrogen mustard, used for ____, with ADRs of ___
Chlorambucil;
CLL and primary (Waldenstrom) macroglobulinemia;
Pulmonary toxicity, secondary leukemia
Carmustine and Lomustine are useful for treating___, but have characteristic toxicity of:
Malignant astrocytoma and malignant brain tumors;
Delayed hematopoietic depression
Anti-tumor antibiotics?
Dactinomycin
Plicamycin
Anthracyclines
What are the anthracyclines?
What is their MOA?
Inhibition of topoisomerase II: Daunorubicin Doxorubicin Idarubicin Eprubicin Mitoxantrone
MOA and uses of Bleomycin:
Causes DNA fragmentation (unique MOA):
Squamous CA of head, neck and lungs
Lymphomas
Testicular tumor
Anti-tumor antibiotic associated with mucocutaneous and pulmonary toxicity:
Bleomycin
Adverse effects of doxorubicin (anti-tumor antibiotic):
Irreversible, dose-related cardiomyopathy
Local tissue necrosis
Red discoloration of urine
Adriamycin flare (benign local allergic reaction)
Adverse effect of cyclophosphamide which manifests as frank hematuria:
Sterile hemorrhagic cystitis
MOA and uses of Dactinomycin:
Causes single stranded breaks in DNA: Rhabdymyosarcoma, Wilm's tumor Kaposi sarcoma Ewing's tumor
Anti-tumor antibiotic associated with local tissue necrosis and radiation recall reaction:
Dactinomycin
Antidote to anti-tumor antibiotics in general, and its MOA:
Dexrazoxane; iron chelator
Uses of Doxorubicin:
BEST agent for metastatic thyroid CA
Acute leukemia
Malignant lymphoma
Breast cancer
Vinca alkaloids bind to __, inhibiting ___ and causing ___ specific arrest:
tubulin; microtubule assembly; M-phase
Viscristine adverse affects?
dose-limiting neurotoxicity of the periphery
Vinblastine adverse affects?
Myelosuppression (B = bone marrow)
Taxanes ___ microtubule assembly and are useful in:
Promote (prevent microtubule disassembly); breast and ovarian cancer
Epipodophyllotoxins are derived from the ____ and inhibit ___
American mandrake; topoisomerase II
Campthecins are derived from ____ and inhibit ____, which causes ___ specific arrest:
The happy tree; topoisomerase I; S-phase
Used in the treatment of endometrial CA?
Megestrol (Progestins)
Palliative treatment for advanced breast CA?
Tamoxifens (anti-estrogen)
___ is an anti-androgen, used in combination with ___ in the treatment of prostatic CA:
Flutamide; GnRH
The cytokine biological response modifiers?
Interferon-a (CML, Kaposi’s sarcoma)
IL-2 (Renal cell CA, Melanoma)
BCG (Urinary CA in situ)
Monoclonal antibody BRM?
(MoAbs/Mabs) Ritixumab + Mabthera
Target CD20 B-cell antigen
Tyrosine kinase inhibitors (TKIs) inhibit the action of ____, ___, and ____
BCR-ABL
c-kit
PDGFR- beta tyrosine kinase
Examples of CCS drugs:
Antimetabolites
Bleomycin
Plant alkyloids
Hormones
Plant alkaloids:
Vinva alkaloids
Podophyllotoxins
Taxanes
Campothecins
Cyclophosphamide is activated to ___ and ___ hepatically:
Phospharamide; acrolein
