Cancer - Group of over 100 diseases that involve tissue invasion, cellular growth and proliferation with distant metastases

Benign - Noncancerous, localized, encapsulated, surgery is curative, seldom metastasize, cells look like those from which they originated

Malignant - Genetically unstable, cells do not look like those from which they originated, tend to metastasize, surgery not curative

- Any regulated process can go awry

- Cancer can happen anywhere:

- Solid Tumors

- Blood/bone marrow

- Lymphatic system

Internal factors:

- Inherited mutations

- hormones

- immune conditions

- mutations that occur during metabolism

Lifestyle:

- ACS estimates that 500,000 new cancers related to nutrition, physical inactivity, overweight/obesity

Oncogenes:

- Develop from proto-oncogenes (normal genes)

- Present in all cells

- Regulate normal cellular functions

- Genetic alteration of proto-oncogene activates the oncogene

- Activation of hte oncogene results in excessive amount or normal or abnormal gene product, and dysregulated cell growth and proliferation. 

- Regulates innappropriate cellular growth and proliferation.

- A loss or mutation of one of these genes results in loss of control over normal cell growth

- p53 is an example of a tumor suppressor gene, and loss or mutation of this can lead to drug resistance and other cancers.

Initiation - Exposure to carcinogen, genetic damage, and mutated cell with selective growth advantage. 

Promotion - Carcinogens, environment, other unknown factors promote growth of mutated cell, mutated cell technically not cancerous

Progression - Continued genetic changes, increased proliferation, tumor invasion, metastases (cell dislodges from local site and gets carried to another part of the body) 

- Gompertzian tumor growth curve

- Initial growth phase is exponential, then levels off

- Chemo most effective against rapidly dividing cells

- Problem is cancer is not detectable until 1cm cell mass, at which point the growth is already plateauing

- 1kg mass is lethal

CAUTION:

C- change in bladder or bowel habits

A- sore throat that doesn't heal

U- Unusual bleeding or discharge

T- thickening or lump in breast elsewhere

I- Indigestion or difficulty in swallowing

O- Obvious change in wart or male

N- Nagging cough or hoarseness

T --> Tumor.  Number indicates size of tumor, usually subscript 1-4, with 4 being the largest

N --> Node.  Indicates extent and quality of nodal involvement, usually subscript 0-3, 0 is best.  Means something different for other cancers

M --> Metastases. Subsript 0 means absent, 1 is present. 

- Early/localized cancer treated with surgery or XRT

- Chemo can be used with other modalities

- Neoadjuvant --> get chemo BEFORE surgery

- Chemoradiation --> combination of radiation therapy, to increase efficacy chemo is given once a week as well (ex: head and neck we won't do surgery)

- Adjuvant --> Chemo is given AFTER surgery

- Stage IV treatment is generally palliative, whatever they can tolerate. 

- Performance status of treatments

- KPS the higher the better, optimal is >60%

- 100% is no evidence of disease, 0% is death

- ECOG is 0-4

- 0 is fully active, able to carry on predisease activity

- 4 is bedridden, completely disabled

- "Good" ECOG is >2

ASCO:  expert panel from variety of backgrounds, updated periodically, evidence-based, few # of guidelines

NCCN:  Expert panel from member institutions (12 large cancer centers), updated yearly, consensus!, comprehensive set of guidelines: diseases, supportive care, screening

*Asco is literature/evidence driven, but not updated regularly

*NCCN is group of experts, purely evidence based, there IS literature to back up their decisions, but they're not all about the RCT and other studies, but they update OFTEN.  If faced with disease state we don't know how to treat/not familiar with, then go to the NCCN

- Primarily patient-centered

- Good for screening/prevention

- Sometimes doesn't have level of information that providers need

- Collect statistical information, ACS interprets this.

- DON'T go here for guidelines. 

- If you're really lost then read patient information here first, THEN provider information to fill in the blanks. 

OS/Median survival - esp. early disease but less so Stage IV

PFS/TTP (progression-free survival/time to tumor progression)

Response rates - may not mean anything be careful

Quality of life - Difficult to assess, not often measured

FACT - Functional Assessment of Chemotherapy Toxicity

- CTC, common toxicity criteria

- grading scheme to indicate severity of a side effect

- Used in clinical trials and practice

- Specific criteria to grade different side effects

- In general:  1 or 2 is mild, 3 is moderate requiring medical intervention, 4 is severe requiring hospitilization, 5 is death

- Generally based on BSA

- Vinchristine 1.4mg/m2

- Motsellar's equation: BSA = square root of [(ht)(wt)/3600]

- Sometimes weight based (Bevacizumab is 10mg/kg)

- Carboplatin based on AUC --> Dose (mg) = (CrCl)(target AUC) + 25

- Two controversies are dosing in obesity, and actual vs. ideal body weight.

*We want to use the Cockcroft-Gault equation, but the controversy remains on whether or not to cap the BSA at 2*

Capecitabine (Xeloda®)

- Check CBC for key parameters: Generally ANC > 1500; PLT >100k; HGB > 8

- Check if renal/hepatic doses necessary

- Calculate BSA (BSA = square root of [(ht in cm)(wt in kg)/3600]

- Calculate dose in mg

- Calculate volume

- Never put VINES IN THE SPINE! NEVER EVER!

- Doxorubicin (Adriamycin) has a max lifetime dose!  Cardiotoxic, give up to 300mg/m2, then give with dexrazoxane, max 550mg/m2.  Check for EF >30%; MUGA scan done prior to dispensing

- Paclitaxel (Taxol) causes severe infusion reactions, not water soluble, Cremophor base believed to cause reactions.  Pre-medication steroids necessary (HC 100mg IV, dexa 20-10mg PO/IV, diphen 25-50mg IV/PO; any dose > 135mg/m2 should be given over 3 hours, less than that should be over 1 hour.  Docetaxel (taxotere) allergy does not mean Taxol allergy

- Cisplatin is reference drug for N/V, most emetogetic agent, always requires 5HT3 antagonist and dexamethasone.  Aprepitant (Emend) is recommended for doses > 50mg/m2

- When writing, DON'T use trailing zero's, DO use leading zero's, write generic names, no abbreviations, include BSA and calculated dose

- Doxorubicin is red, Mitoxantrone is dark blue, Leucovorin is yellow.