Path: principles of cancer therapy Flashcards
What is required to definitively diagnose cancer?
histologic analysis
What is the difference between clinical staging and pathological staging?
clinical staging: physical examination and imaging studies like CT, PET scands, and radionucleotide scans.
pathologic staining more definitive and follows the tumor-node-metastasis method.
What goes into the TNM staging model?
tumor: size and extent of primary tumor
N: number and logation of histologically involved lymph nodes
M: presence of absence of metastasis
What is the purpose of the ECOG or Karnofsky scales/
useful for making treatment decisions around palliative chemo for cancer. these tests assess performance status and give us an idea of how much time the patient is spending out bed and doing their normal activites; if patient is very sick, chemo may not be the best option.
What are some advantages of radiation?
might be definitive treatment
may preserve organ structure and function, leading to better quality of life
In what unit is the dose of radiation measured? What is one way to dose chemo?
units of absorbed dose, the Gray.
ways to dose chemo: divide the ttotal planned radiation dose into small daily fractions to take advantage of different repair properties of malignant vs. benign tissues.
In what ways can radiation be delivered? Which kind is best for different types of tumors?
as external beam therapy with linear accelerator to generate electrons or as high energy X-rays. electrons are best for superficial tumors because electrons have limited depth of penetration.
meanwhile, X-rays deliver the dose deep in the body
What is brachytherapy?
uses radioactive sources to deliver ionizing radiation directly to the tumor- ex. is the implantation of iodine 125 seeds into the prostate as definitive therapy for early prostate cancer.
What are some complications of radiation therapy?
acute effects; within days to weeks; seen in rapidly proliferting cells like skin and GI mucosa. generally can be repaired.
late effects: necrosis/fibrosis/organ failure: months to years after irradiation. depend on fraction size.
development of secondary malignancies.
What are four classifications of chemotherapy agents?
alkylating agents, antimetabolites, antitumor antibiotics, and mitotic spindle inhibitors.
What is a common side effect of many chemotherapy agents?
bone marrow suppression, which can lead to infection.
What should I know about dosing and chemotherapy?
the dose response curve is steep- a little increase in dose can dramatically increase cancer kill rate; a little decrease can damatically decrease kill rate. no arbitrary dose reductions! Also, if you can shorten cycle duration by supporting pts with growth factor to promote recovery, you see better survival.
What is adjuvent vs. neoadjuvent therapy?
adjuvent: use of chemo after the primary tumor has been resected. chemo directed against presumed systemic micrometastases in patients believed to be at high risk for recurrence.
neoadjuvent: use of chemo before surgery, sometimes in combo with radiation. may reduce tumor size and permit lesser surgery.
complete response vs. partial response
follow all known sites of disease via physical exam and serial radiologic imaging
disappearance of all known sites of disease is called a complete response.
30% or more reduction in long diameter is a partial response
What is tumor progression?
appearance of new lesions or an increase in the size of known lesions by 20%
What is stable disease?
A tumor that does not progress or respond to treatment
What is the definition of response rate?
the percent of patients who experience a response
What is the gold standard for measruing efficacy?
improvement in survival or disease free survival
What is one of the most important forms of cancer resistance to chemotherapy?
intrinsic resistance mediated by an evolutionarily conserved cell membrane efflux pump called P-glycoprotein.
Why might allogenic bone marrow transplants be more effective than autologous transplants at inducing cures?
graft-versus-malignancy effect
What is imatinib?
used to treat chronic myelogenous leukemia by inhibiting brc-abl (constitutively active fusion product from the philadelphia chromosome).
What is bevaciumab?
an anti-angiogenic agent directed against the pro-angiogenic VEG-F. increases response rates and survival when combined w/ standard chemotherapy in advanced colon cancer. may also have implications for renal and lung cancers.
What are biologic response modifiers/ biologic agents?
cytokines that use host immunomodulatory effects as their primary mechanism of action
What is an example of a biologic response modifier/biologic anti-cancer agent?
interferons for the treatment of chronic myelogenous leukemia; hairy cell leukemia, kaposi’s sarcoma, melanoma/renal cell carcinoma.
When can IL-2 be used and what kind of therapy is it?
IL-2 can be used to promote T-cell activity and can induce responses in patients with metastic melanoma or renal cell carcinoma.
What is a toxicity associated with IL-2?
hypotension, edema, renal insufficiency, death.
What drugs are used to help control chemotherapy induced nausea?
serotonin receptor antagonists and neurokinin-1 receptor antagonists
What drugs are used to help treat neutropenia secondary to chemotherapy? Other uses?
granulocyte-colony stimulating factor/filgrastim and granulocyte-macrophage stimulating factor/sargramostim. filagrastim also used to shorten the duration of chemo cycles
induction therapy vs. consolidation therapy
induction therapy: primary treatment for advanced cancer which has no alternative treatment
consolidation therapy: follows induction/primary therapy for maintenance
What are four key classes of ctotoxic chemotherapy agents?
antimetabolites, alkylating agents, intercalating agents, and spindle poisons
How do intercalating chemo agents work?
prevent DNA transcription and DNA duplication
How do alkylating agents work?
chemical modification of guanine and interference with DNA replication and transcription to RNA. cell-cycle phase non-specific
How do antimetabolites work?
prevent DNA synthesis
How do spindle poisons work?
prevent mitosis
How do antitumor antibiotics work?
polyfunctional but mostly bind DNA, cause uncoiling/breakage of the helix, and impair DNA and RNA synthesis.
What kind of drug is methotrexate
antifolate antimetabolite
How do topoisomerase inhibitors work?
target nuclear enzymes DNA topoisomerase II and topoisomerase I
What are two drugs associated with cardiomyopathy and cardiac toxicity (chemotherapy for cancer)
doxorubicin (DNA intercalator)
trastuzumab
For what women might aromatase inhibitors be effective in breast cancer?
post-menopausal women
How does fulvestrant work?
inhibits estrogen receptor dimerazation and promotes receptor degradation
How doues lupron work>
sustained stimuation of the pituitary makes the pituitary insensitive and reduces LH and FSH production
What is the classic example of a signal transduction inhibitor?
imatinib.
