Oncology

EX. Carboplatin, chlorambucil, cisplatin, cyclophosphamide, ifosfamide, oxaliplatin. Alkylation of DNA is the crucial cytotoxic reaction. Cell cycle non-specific but most toxic to rapidly dividing cells. SE-NV (cisplatin)

Ex. capecitabine, cytarabine, fluorouracil, gemcitabine, methotrexate. Cell cycle specific. Inhibit growth & proliferation by competing for binding sites on enzymes & incorporation into DNA or RNA.

Ex. bleomycin, doxorubicin, epirubicin. Cell cycle non-specific. Binds to DNA causing breakage, & inhibits RNA synthesis SE-pulmonary toxicity (bleomycin), cardiac toxicity (doxorubicin)

Paclitaxel, docetaxel. G2 and M phases. Inhibits mitosis b/c of antimicrotubule effect. Plant alkaloid. SE-hypersensitivity, neurologic toxicities

Irinotecan, topotecan. S phase. Topoisomerase-I inhibition, resulting in DNA breakage. Plant alkaloid

etoposide, teniposide pre-mitotic G2 & S phases Topoisomerase-II inhibitor causing DNA breakage. Plant alkaloid. SE-hypersensitivity

Vinblastine, vincristine, vinorelbine. act in G2 and M phases. Anti microtubular agent inhibits mitosis. Plant alkaloid SE- Autonomic (constipation), and peripheral neurotoxicity

Tamoxifen, toremifene-Inhibit binding of the estrogen receptor Megestrol-suppresses adrenal steroid synthesis. SE-increased risk of blood clots, hot flashes

Anastrozole, letrozole, Fulvestrant prevents conversion of androgens to estrogens in fat tissue

Trastuzumab, rituximab (ends in mab) Marks cell for attack by immune system, delivers antitumor agent, blocks cell receptors. SE-hypersensitivity/anaphylaxis, cardiac toxicity (trast), wound dehiscence (bevac), acne like rash (cetux)

Ondansetron, granisetron (end in setron) Selectively block serotonin 5-HT3 receptors in the GI tract and the CTZ. Useful for N/V side effects. SE-headache, diarrhea, constipation

Prochlorperazine, Trimethobenzamide. Blockade of dopamine receptors in the CTZ (relieves N/V)-SE-sedation, hypotension, EPS

Dexamethasone, Methylprednisolone. For N/V, decreased appetite

Dronabinol. Used for N/V, decreased appetite. Likely due to depression of higher cortical pathways leading to emetic center.

Lorazepam. Amnestic, anxiolytic, and sedative

Goserelin, Leuprolide. Hormonal negative feedback loop that results in suppression of the release of testosterone and estrogen. SE-Bone mineral density loss (Leuprolide)

Bicalutamide, Flutamide, Nilutamide. Nonsteroidal agents that competitively inhibit the binding of androgens to the androgen receptors in the prostate.

Blocks expression of oncogene or replace missing/defective tumor suppressor gene

Interferes with proteins involved in apoptosis, causing cell death

Prevents the growth of blood vessels to support tumor cells

Imatinib (tyrosine Kinase inhibitor)Gefitinib, Erlotinib (EGFR-TK inhibitor)Block enzymes and growth factor receptors involved in tumor cell growth

Chemotherapeutic agent associated with pulmonary fibrosis

Chemotherapeutic agent associated with hemorrhagic cystitis

Chemotherapeutic agent associated with cardiomyopathy

Chemotherapeutic agent associated with renal toxicity

chemotherapeutic agent associated with skin pigmentation

Tumor with good response to chemo

Tumor with good response to chemo

Tumor with good response to chemo

Tumor with poor response to chemo

Tumor with poor response to chemo

Tumor with poor response to chemo

Blocks HER2 receptors

The ability of a test to rule out a disease

The percentage of people with cancer who will have an abnormal test

The percentage of people without cancer whose test is negative

The ability of a test to rule in disease

Probability that people with an abnormal test actually have cancer

Probability that a negative test will predict that a person does not have cancer

Proteins normally found in larger amounts during fetal development

These are examples of which type of tumor marker; AFP, CEA, PSA, CA-125, Bence Jones Proteins

These are examples of which type of tumor marker; Prostatic Acid Phosphatase, Galactosyl transferase II

This marker is often associated with tumors of endocrine glands

These are examples of which type of tumor marker; Beta-HCG, Human Calcitonin

Genes that are useful in fetal development but when activate in mature cells trigger tumor growth

These are examples of which type of tumor marker; BRCA 1, BRCA 2, Philadelphia chromosome

Philadelphia Chromosome is associated with which type of cancer

Cell surface proteins that affect the rate of tumor development by binding to hormones and growth factors

These are examples of which type of tumor marker; ER assay, PR assay, EGFR

What goes down as prevalence of disease goes down

Increased in 80-90% of patients with hepatocellular carcinoma

Patients with cirrhosis and active hepatitis should be screened with which tumor marker every 3-4 months

Used primarily to detect and monitor clinical course of Multiple Myeloma. It is not found in the blood b/c it is efficiently filtered by the kidneys. Considered to be the first tumor marker.

This hormone tumor marker is normally negative except in pregnancy, and is never found in cancer free males.

This hormone tumor marker is primarily associated with the following; Hydatidiform mole of the uterus, choriocarcinoma of the uterus, and germ cell tumors of the ovaries

High levels of this hormone are almost always pathognomonic for germ cell neoplasm in men.

This antigen is useful in diagnosis, evaluation of therapy, and surveillance in patients with pancreatic and hepatobiliary cancer

This antigen is elevated in 80-90% of women with ovarian cancer.

This antigen is used in determining the extent of disease, prognosis, and response to therapy in patients with GI cancers.

Baseline for this antigen is elevated in smokers.

This antigen is used in screening for early detection of prostate cancer.

When combined with a digital rectal exam 90% of clinically significant cancers can be detected.

Not a tumor marker but a useful diagnostic tool for assessing risk of developing breast cancer in a woman in the general population

This tool takes into account these factors when assessing 5 year and lifetime risk of developing breast cancer; current age, age at menarche, previous breast biopsies, age at first live birth, family history of breast cancer.

Breast cancer oncogenes

Men with this mutation carry a markedly increased risk of developing prostate cancer and or colorectal cancer, and may pass the mutation to their daughters.

This tissue receptor indicates sensitivity to hormonal therapy.

Tumors positive for this tissue receptor are more than twice as likely to respond to hormone therapy.

This tissue receptor is more often positive in postmenopausal breast cancer patients

An increased level of this antigen is associated with more aggressive breast cancers.

Triple negative tumors have no hormonal target for therapy and are negative for which markers.

This antigen is elevated in 70-80% of patients with metastatic disease, and is rarely elevated in early stage disease.

This antigen is useful in monitoring response to therapy in metastatic breast cancer patients.

This rare marker is associated with liquid tumors; lymphoma, leukemia, multiple myeloma.

This rare antigen is not a good screening tool b/c levels can be elevated in UTI, renal calculi, recent urinary surgery

This rare marker is a good screening tool for patients at risk for bladder cancer

A sensitive marker for detection of bladder cancer across all disease stages and grades

This hormone is used to evaluate patients with at risk for/suspected medullary carcinoma of the thyroid.

This enzyme is associated with Neuroblastoma, carcinoid, and small cell lung cancer

This enzyme is primarily used to diagnose, stage, and monitor efficacy of treatment in prostate cancer

This cancer has a 30% recurrence rate even decades after successful treatment

This protein is the primary marker for surveillance of well-differentiated thyroid cancers in postoperative patients.

Common tumor marker for ovarian cancer

k-ras, c-myc, abl, Her2/neu are all examples of what

Genes that once mutated activates the growth pathway

Only one copy needs to be mutated to induce tumorigenesis

Genes that normally inhibit growth

A mutation of these causes a loss of inhibition

Both copies need to be mutated to lose function

Classic presentation of this type of cancer is painless jaundice

Tumor marker for teratoma

No meat

Tissue

In what scenario do you not need a pathological specimen to initiate treatment

A small needle is inserted into the mass and cells are removed for microscopic evaluation

Can be done guided or unguided

This type of biopsy is mainly applied to melanoma

What type of biopsy is not indicated for suspected melanoma

Once a tissue diagnosis positive for cancer is obtained what is the next step in treatment of the patient

Based on the theory that lymphatic spread proceeds through a consistent anatomic network of ducts and nodes based on tumor location

Looking for hot and blue nodes

It is recommended that those with this disorder start having colonoscopies in their teens

Should begin screening 10 years prior to the age of onset in the family member affected with what cancer.

Cyclophosphamide

Ifosfamide

Oxaliplatin

Temozolomide

Doxorubicin

Capecitabine

Gemcitabine

Pemetrexed

Vinblastine

Vincristine

Paclitaxel

Paclitaxel – nanoparticle albumin bound

Docetaxel

Topotecan

Irinotecan

Cisplatin

Carboplatin

Oxaliplatin

Bicalutamide

Anastrozole

Letrozole

Erlotinib

Imatinib

Alemtuzumab

Trastuzumab

Bevacizumab

Rituximab

Cetuximab

Cyclophosphamide/ Cytoxan

Ifosfamide/ Ifex

Oxaliplatin/ Eloxatin

Temozolomide/ Temodar

Doxorubicin/ Adriamycin

Capecitabine/ Xeloda

Gemcitabine/ Gemzar

Pemetrexed/ Alimta

Vinblastine/ Velban

Vincristine/ Oncovin

Paclitaxel/ Taxol

Paclitaxel – nanoparticle albumin bound/ Abraxane

Docetaxel/ Taxotere

Topotecan/ Hycamtin

Irinotecan/ Camptosar

Cisplatin/ Platinol

Carboplatin/ Paraplatin

Oxaliplatin/ Eloxatin

Bicalutamide/ Casodex

Anastrozole/ Arimidex

Letrozole/ Femara

Erlotinib/ Tarceva

Imatinib/ Gleevec

Alemtuzumab/ Campath

Trastuzumab/ Herceptin

Bevacizumab/ Avastin

Rituximab/ Rituxan

Cetuximab/ Erbitux

Used in high risk populations to prevent cancer

Used before surgery to shrink tumor; less “radical” surgery

Used after surgery to eradicate micro-metastases

Used in high doses to obliterate the bone marrow as preparation for transplantation

Eradication of disease; Complete response ≥ 5 years

Extension of life when cure is not possible

Comfort when cure or control is impossible; Reduction of tumor burden that relieves associated symptoms & side effects, including pain

interferes with cell proliferation in various ways.

Resting Phase

Post-mitotic Phase; Enzymes needed for DNA synthesis are produced & RNA synthesis is occurring

DNA produced in preparation for cell division

Pre-mitotic/Post-Synthesis Phase. Cell makes RNA & proteins for cell division

Cell division occurs

Class of DRUGS that act on phase: M

Class of DRUGS that act on phase: G2

Class of DRUGS that act on phase: S

Class of DRUGS that act on phase: all phases

Mechanism: Alkylation of DNA

Common side effects: Myelosuppression; Hypersensitivity; Renal; GI; Secondary malignancies

Mechanism: Binds to DNA, causing breakage; Inhibits RNA synthesis

AE: Myelosuppression; GI; Cutaneous; Pulmonary toxicity ; Cardiac toxicity

Mechanism: Similar to normal cellular substances, and when incorporated into cell, make unable to divide.

AE: Myelosuppression; GI (diarrhea); Cutaneous

Camptothecins; Epipodophyllotoxins; Taxanes; Vinca alkaloids; Derived from plants; Cell cycle specific

Mechanism: Topoisomerase-I inhibitor; Act in S phase

Common side effects: Myelosuppression; Alopecia; GI

Common side effects: Hypersensitivity, Myelosuppression, GI, Hypotension

Mechanism: Topoisomerase-II inhibitor; Act in G2 and S phases

Mechanism: Anti microtubular agent; Inhibits mitosis; Act in G2 and M phase

Common side effects: Hypersensitivity, Myelosuppression, Cutaneous, Neurologic Toxicities

Mechanism: Anti microtubular agent; Inhibits mitosis; Act in G2 and M phases

Common side effects: Myelosuppression, CONSTIPATION and Peripheral Neurotoxicity

Bind to estrogen receptors on tumor surface; Prevent cell growth/cause cell death

Block aromatase enzyme, which converts androgens to estrogen; Absence of estrogen causes tumors to shrink

Inhibit the binding of testosterone to the androgen receptors in the prostate

Leuteinizing hormone-releasing hormone; Signals pituitary gland to stop releasing LH Direct effect on testicles & ovaries

Target specific antigens on cancer cell surface Marks cell for attack by immune system Blocks specific receptors Delivers anti-tumor agent

Side effects Infusion reaction (hypersensitivity/anaphylaxis) – ALL! Cardiac toxicity (Trastuzumab)Bleeding/wound dehiscence (Bevacizumab)Skin rash (Cetuximab)

anti HER2

anti CD20

anti CD52

EGFR

Protein secreted by cancer cells to promote new vessel formation

Stimulate immune system (MAb’s)

Interleukin, interferon

Most common dose-limiting toxicity of chemotherapy

ANC = 1500 to 2000

ANC = 1000 to 1500

ANC = 500 to 1000

Severe

CINV: Occurs within 24 hours; Incidence determined by agents

CINV: Occurs at least 24 hours after therapy and may persist up to 6 days; Cisplatin associated with highest incidence

CINV: Occurs before or during treatment from associated stimuli; a conditioned response; 25% incidence

MOA: Selective blockade of serotonin 5-HT3 receptors in the GI tract & the brain

AEs: Headache, diarrhea or constipation

MOA: Blockade of dopamine receptors in the CTZ

AEs: Sedation, hypotension, EPS

AEs: insomnia, hyperglycemia, increased appetite, euphoria, agitation/anxiety

MOA: Unknown.

Improves nausea, appetite and pain

MOA: Amnestic, anxiolytic, and sedative properties

AEs: Sedation, hypotension, disinhibition, motor incoordination

Irinotecan !!!Fluorouracil; Topotecan-Capecitabine

Vincristine - Vinorelbine; Vinblastine

Inflammation of the GI mucosa

Inflammation of the oral mucosa

Anthracyclines Doxorubicin, Epirubicin Early or late onset LV dysfunction, dose related

Trastuzumab (Herceptin)LV dysfunction Often reversible if drug discontinued

CT, MR

Radiographs, CT, PET

Mammography, US, (MR)

Colonoscopy (conventional vs. virtual), CT, PET

US, MR

Radiographs, CT, MR; PET to trouble shoot

Cellular products that are helpful in the detection, diagnosis, and therapeutic management of certain cancers

The percentage of people with cancer who will have an abnormal test

The ability to identify people who have the disease

The percentage of people without cancer whose test is negative

The ability to identify people who do not have the disease

Probability that people with an abnormal test actually have cancer

Probability that a negative test will predict that a person does not have cancer

Five general categories of tumor markers:

Proteins normally found in larger amounts during fetal development. Cancers contain undifferentiated cells that may carry surface markers of their fetal predecessors; these cells often manufacture antigen proteins in increased quantities

AFP, CEA, PSA, CA-125, Bence Jones Proteins

Blood plasma levels of these proteins may be increased in malignant tissue; Measured by immunoassay

Prostatic Acid Phosphatase, Galactosyl transferase II

Beta-HCG, Human Calcitonin

Either larger-than-normal amounts of the hormone usually secreted by the specific tissue Or hormonal production by tissue which does not normally produce that hormone

Or hormonal production by tissue which does not normally produce that hormone

Genes that are useful in fetal development but when activated in mature cells trigger tumor growth

BRCA 1; BRCA 2;Philadelphia chromosome

Cell surface proteins that affect the rate of tumor development by binding to hormones and growth factors

ER Assay, PR Assay, EGFR

A test designed to detect cancer in an asymptomatic person

An abnormal level of a tumor marker increases suspicion of cancer over a similarly presenting non-malignant condition

Extremely high values may be

Most tumor markers are used to monitor patients for recurrence of cancer following treatment

Antigen used to screen patients with a high risk of developing hepatocellular carcinoma (HCC)

ANTIGEN used primarily to detect and monitor clinical course of Multiple Myeloma

found in multiple myeloma and in patients with leukemia, lymphoma, and bone metastases

HORMONE: Glycoprotein produced by placental tissue; Normally negative except in pregnancy

Hydatidiform mole of the uterus Choriocarcinoma of the uterus Germ cell tumors of the ovaries Also elevated in hepatoma

Never found in normal males High levels are almost always pathognomonic for germ cell neoplasm in men

Antigen: pancreatic and hepatobiliary cancer

ANTIGEN: ovarian cancer

ANTIGEN: prognosis, and response to therapy in patients with GI cancers* Discovered in colorectal cancer, but also useful in other malignancies: Breast, pancreas, gastric, hepatobiliary, small cell lung cancer

Elevated baseline levels found in smokers

Antigen: prostate cancer

oncogenes: development of breast cancer & ovarian cancer

Men with a BRCA mutation carry a markedly increased risk of developing prostate cancer and/or colorectal cancer; May pass mutation to their daughters

TISSUE RECEPTOR: breast cancer

ANTIGEN: aggressive breast cancers

ER-/PR-/HER 2 -

ANTIGEN: First breast cancer tumor marker available; Rarely elevated in early stage disease; Elevated in 70-80% of patients with metastatic disease

ANTIGEN: early stage patients have elevated levels & 65% of patients with metastatic disease have elevated Useful in monitoring response to therapy in metastatic breast cancer patients

Corresponds to tumor burden, prognosis, and response to therapy in liquid tumors: Lymphoma; Leukemia

Bladder Cancer Markers

GI cancers

Hormone level used to evaluate patients with suspected medullary carcinoma of the thyroid

Neuroblastoma; Carcinoid; Small cell lung cancer

Enzyme primarily used to diagnose, stage, and monitor efficacy of treatment in prostate cancer

Primary tumor marker for surveillance of well-differentiated thyroid cancers in post-operative patients

number of newly diagnosed cases during a specific time period

new and existing cases for people alive on a certain date

overall or disease-free

probability of developing or dying of cancer

Commonly diagnosed cancers

Leading cause of death from cancer

Diagnostic testing which is intended to detect a disease or identify risk for disease, in an asymptomatic patient

Mammography not recommended ages 40-49

Mammography recommended ages 50-74 yr – every 2 years

Teaching self-breast examination not recommended

Insufficient evidence to assess clinical breast exam utility

Insufficient evidence for additional benefit of digital mammography or MRI

Women at high risk (Criteria=family history) –refer for genetic counseling and BRCA testing

Women not at risk (criteria- no family history) – recommend against referral for hereditary counseling or BRCA testing (2005)

recommendation for PAP (conventional) starting age 21 or within 3 yrs of first sexual activity (whichever occurs 1st). PAP every 3yrs

Recommends against routine screening over age 65 if previously normal exams, in average risk patient; or after complete hysterectomy

insufficient evidence for HPV DNA as primary screening.

recommends against PAP screening if total hysterectomy for benign disease

Insufficient evidence to recommend for or against new screening technologies

Ovarian Cancer: Available tests :CA125; Transvaginal Ultrasound; Recommends against routine screening.

Colorectal Cancer: age 50 - 75 if average risk

recommend against CRC screening in age 76-85, with individual patient consideration for benefits.

recommend against screening in adults over 85 years of age.

insufficient evidence to assess balance of benefit/harm for CT colonoscopy or DNA testing

Use of Aspirin or NSAID as chemoprevention of CRC (2007)- Potential harm outweighs potential benefit

Lung Cancer: Available Procedures: CXR; Sputum Cytology: Low-dose/helical/spiral CT: insufficient evidence for all 3 procedures

Prostate Cancer: Insufficient evidence to consider balance of benefit/harm for men < 75.

Prostate Cancer: against screening in men > 75.

Bladder (2004)Pancreatic (2004)Testicular (2004)

Oral Skin Thyroid