Chemo Drugs I Flashcards
How many cell doublings are typically needed for cancer to be clinically detectable?
Around 30 (could take years to develop)
List the 4 stages of metastasis
- clonal evoution
- intravasation
- extravasation
- growth in the distant metastatic site
What is the Skipper Hypothesis?
The ability of chemotherapy to cure is inversely proportional to the tumor burder
What are two big factors in the development of chemoresistance?
Faster mutation rate and Time
Treating early is better, before development of chemoresistance
Describe
- Complete remission
- Partial remission
- Stable disease
- Progression of Disease
Complete remission is NOT cured. You have killed enough cells that you no long see them
Partial remission– over 50% reduction of tumor size with no new lesions
Stable disease– nothing changed with chemo (didn’t grow, didn’t shrink)
Progression of disease (worsened)
What is the purpose of Phase I, II, and III chinical trials?
Phase I – determine dose and dose limiting toxicity
Phase II – determine activity
Phase III – determine efficacy
What is the ANC? How is it used?
Absolute Neutrophil Count = (% segs + % bands) x Total leukocytes
Low ANC and a fever – need to be admitted with cultures drawn
Start broad spectrum ABX until PMN count begins recovering
Ondansetron MOA
5HT3 antagonist used as an anti-emetic agent
Blocks 5HT3 receptors in the CTZ of the area postrema
AEs: Constipation, risk of QT prolongation
Alkylating Agents
MOA
Binds covalently to DNA
-Sulfur avid
Cell cycle non-specific
Cyclophosphamide
MOA
Activated in the liver by a P450 oxidase
Phosphoramide Mustard is the DNA damaging agent that binds DNA via its chlorethyl groups
Alkylation may be intrastrand or interstrand
Cyclophosphamide
AEs
N/V
Hair loss
Myelosuppression
Hematuria can occur, but it is not problematic at standard doses
Cyclophosphamide
Indications
Breast Cancer
Non-Hodgkin lymphoma (diffuse large B cell lymphoma)
How is Ifosphamide different than Cyclophosphamide?
Ifosphamide only has 1/5 the alkylating activity of Cyclophosphamide, so it needs to be given at higher doses
Ifosphamide
Coadministered with…?
Coadministered with Mensa, which is protective against Ifosphamide’s hematuria side effects
Ifosphamide
Indications
Soft tissue sarcomas
Testicular cancers
Temozolamide
MOA
Monofunctioning alkylating agent
Methylates the DNA
Temozolamide
Indications
Glioblastoma and other primary brain tumors
Temozolamide
AEs
N/V, hair loss, myelosuppression
Must give prophylaxis against PCP pneumonia
Platinum Coordinating Compounds
General MOA
Alkylating agents with Platinum in +2 oxidation state
What are the 3 main Platinum Coordinating Compounds?
Cisplatin
Carboplatin
Oxaliplatin
General Mechanism of resistance to DNA alkylating agents
Nucleotide excision repair molecules can break the alkylating agents
Cisplatin
Indications
Testicular cancer (curative)
Lung, ovary, head and neck, bladder cancers too
Cisplatin
Dose limiting toxicity
Nephrotoxicity (high doses will ruin the kidneys)
Cisplatin is also excreted by the kidneys, so it is often given with saline and maybe a mannitol diuretic. Therefore burdensome to administer in clinic
Cisplatin
Contraindications
Renal impairment
Impaired cardiac or respiratory function (may not handle the high fluid load taken with cisplatin)
Carboplatin
Indications
Testicular cancer (curative)
Lung, ovary, head and neck, bladder cancers too
MAY be given to someone on dialysis
Carboplatin
Dose limiting toxicity
Myelosuppression
Why would carboplatin be preferred over cisplatin?
Carboplatin is also excreted by the kidneys, but it is NOT nephrotoxic.
You can give carboplatin to someone on dialysis or someone who couldn’t handle the fluid overload with cisplatin
Oxaliplatin
Indications
Colorectal cancer (doubles survival)
Oxaliplatin
AEs
Myelosuppression
N/V
Vein irritant
Acute cold induced neuropathy
Chronic sensory neuropathy
Jaw pain with FIRST CHEW after oxaliplatin (it goes away)
Vincristine
MOA
Prevents polymerization of tubulin in M phase (cell cycle specific)
Vincristine
AEs
Neuropathy is dose limiting (esp if they lose fine motor activity)
Vincristine
Indications
Lymphoma
Hodgkin disease
Lymphoblastic Leukemia
Paclitaxel (Taxol)
MOA
Prevents tubulin disassembly (M phase specific)
Paclitaxel (Taxol)
AEs
Hepatic metabolism
Myelosuppression, hair loss, N/V, stomatitis, peripheral sensory neuropathy
Paclitaxel (Taxol)
Indications
Ovarian, Lung, GI, Breast cancers
Etoposide
MOA
Produces DNA double stranded breaks by targeting topoisomerase II
Blocks G1 –> S
Etoposide
AEs
N/V, hair loss, Myelosuppression
Reduce dose in renal or hepatic dysfunction
Etoposide
Indications
Testicular Cancer
Lung cancer
Lymphomas
