Oncology Update in GI Cancer Tiffany Sipe FNP-BC, MSN,OCN Oncology Nurse Practitioner Tennova Physicians Services

Disclosures Tiffany is on the speakers bureau for Alexion Pharmaceuticals and IMER.

Outcomes at the end of the presentation the participant will: Better understand the most recent data regarding digestive tract cancer rates in the U.S. Recognize new treatment options for GI cancers Identify at least two unique side effects related to new agents used to treat digestive tract cancers Understand the role of targeted therapies in Digestive Tract Cancers

Estimated New Cancer Cases 2011 All Sites- Both Sexes 1,596,670 Females Breast 230,480 Lung 106,070 Colon & Rectum 69,360 Uterine 46,470 Pancreas 21,980 (3%) Cancer Statistics, 2011, A Cancer Journal for Clinicians, Vol.61 (4). Males Prostate 240,890 Lung 115,060 Colon & Rectum 71,850 Urinary Bladder 52,020 Pancreas 22,050 (3%)

Estimated Deaths 2011 All Sites-Both Sexes 571,950 Females Lung 71,340 (26%) Breast 39,520 (15%) Colon & Rectum 24,130 (9%) Pancreas 18,300 (7%) Cancer Statistics, 2011, A Cancer Journal for Clinicians, Vol.61 (4). Males Lung 85,600 (28%) Prostate 33,720 (11%) Colon & Rectum 25,250 (8%) Pancreas 19,360 (6%)

Rocky Top You’ll Always Be Home Sweet Home to Me?? TennesseeAlabamaFloridaOregon All Sites: 34,750All Sites:25,530All Sites: 113,400All Sites: 21,180 CRC: 3,170CRC: 2,310CRC: 10,180CRC:1,730 Lung: 5,870Lung: 4,240Lung: 17,150Lung: 2,860

Digestive Tract Statistics 2011 Esophagus New Cases: Male: 13,450 Female: 3,530 Deaths: Male: 11,910 Female: 2,800 Cancer Statistics, 2011, A Cancer Journal for Clinicians, Vol.61 (4). Stomach New Cases: M ale: 13,120 Female: 8,400 Deaths: Male: 6,260 Female: 4,080

Gastric Cancer Highest incidence occurs in eastern Asia, Andean regions of South America and Eastern Europe Overall incidence of gastric cancer is declining but there is an increase in cancer of the GE junction No routine screening for GC Often asymptomatic- patients are often diagnosed with regional or distance metastasis leading to poor overall prognosis

Colorectal cancer is the third most commonly diagnosed cancer in men and the second in women worldwide. Prostate, Breast, Lung and Colon Cancer are the most commonly diagnosed cancers in men and women Lung Cancer is the leading cause of cancer death in men and women. Colo-rectal cancer is the third leading cause of cancer death in men and women Pancreatic is fourth leading cause of cancer death in men and women

Treatment options for colon cancer Surgery Radiation-more likely used in rectal cancer or for palliative treatment Chemotherapy Targeted Therapy Best Supportive Care

Staging of Colon Cancer Stage O-”carcinoma in situ”-abnormal cells are found in the mucosa of the colon wall. Stage I- formed in the mucosa and spread to the submucosa. May have spread to the muscle layer of the colon wall. Stage II-( A,B,C). Spread through the muscle layer of the colon wall to the serosa, through the serosa or through the serosa and nearby organ. Stage III-(A,B,C)spread through serosa to nearby lymph nodes Stage IV-Spread to distant lymph nodes and other organs. Most common site of metastasis is liver and lung. 2011, NCIwww.cancer

Oncotype DX Colon Cancer Assay First Commercial Test to provide a quantitative Recurrence Score for patient with Stage II Colon Cancer Requires either 1- fixed paraffin-embedded tumor block or 15 unstained slides Incorporates number of nodes examined, tumor size, micro- metastatic lymph or vascular invasion, tumor grade and MMR status Written report available in 10 days with a recurrence score, 5 yr vs 3 yr colon cancer recurrence estimations and relevance for chemotherapy benefit 2011, Oncotype DX Insert

Oncology Terminology Neoadjuvant Treatment Adjuvant Treatment 1 st line, 2 nd line, salvage treatment Palliative Treatment Best Supportive Care Hospice ONS NCCN Guidelines

Chemotherapy 101 “Traditional” chemotherapy side effects: 1. Neutropenia 2. Anemia 3. Thrombocytopenia 4. Nausea/Vomiting 5. Diarrhea 6. Mouth Sores 7. Fatigue 8. Alopecia

Commonly used cytotoxic agents for GI cancer Esophageal/Gastric: Taxotere, Carboplatin, Xeloda, Herceptin*,Adriamycin Colo-rectal: Oxaliplatin, Leucovorin, 5FU, Xeloda, CPT-11, Erbitux*,Vectibex,Avastin

Capecitabine (Xeloda) Oral tablet used in breast, stage III adjuvant and metastatic CRC Can be used as single agent or in combination with radiation or chemotherapy. “Sensitizing agent” Taken with a full glass of water with meals twice daily- cycle length dependent on physician/ mode of administration Vitamin B6 helps prevent “hand and foot syndrome” Similar to 5FU

Eloxatin (Oxaliplatin) First approved in 2003 for metastatic treatment of CRC Approved in 2004 for first line treatment in Stage IIICRC Given with Leucovorin Cold Sensitivity for 48 hours post treatment Peripheral Neuropathy Given every 2 weeks for 6 months as adjuvant treatment in Colon cancer stage II and III -FOLFOX Given every 2 weeks for 4-6 months as adjuvant treatment in rectal cancer Eloxatin Package Insert, 2011

Targeted Therapies..The New Frontier

Epidermal Growth Factor Receptor

K-Ras

Cetuximab (Erbitux) EGFR wild type, metastatic CRC Binds Epidermal Growth Factor Receptor inhibiting cell growth and survival Squamous cell Head and Neck Ca in combo with XRT Requires a loading dose then weekly maintenance dose Premedicate with antihistamines Post reaction transfusion related hypotension- usually one to two hour post infusion observation No renal or hepatic dosing decrease required

Panitumumab (Vectibix) Approved for EGFR expressing metastatic CRC Resistance to therapy if there is a K-RAS mutation in codon 12 or 13 6mg/kg IV every 14 days Acneform Rash Infusion Reactions

Acneform Rash Maculopapular rash that occurs primarily on the face and chest. See handout for photo for examples

Her 2-Neu Human epidermal growth factor receptor 2 Approximately 20% of gastric cancers Normally 20,000 receptors on cell. Her-2 Neu gene amplification can lead to overexpression of Her-2 Neu- 2,000,000. Overexpression means the cancer cell will have excellarated proliferation, survival, motility and adhesion. It is thought that Her-2 positive status in GC is associated with poor outcomes and aggressive disease-conflicting data

Testing for Her-2 Neu Immunohistochemistry (IHC) A sample of tissue is stained and read by a pathologist. According to how much of the tissue “takes up” the stain is the grading it will receive. Grade 2-equivocal, 3 or 4=Her 2 neu + Fluorescense in situ hybridization (FISH) Probes specific for Her-2 neu & a control are placed in the tissue. Ration of Her 2 to control are recorded.>2.2 is Her 2 Neu+

IHC Staining

Trastuzumab (Herceptin) Monoclonal Antibody Approved for Her-2 Neu over expressing Metastatic Gastric Cancer (Esophagus to stomach) ECHO prior to first dose then periodically throughout treatment. Caution in cardiac disease Loading dose (8mg/kg IV X 1) then 6mg/kg/IV every 3 weeks with chemotherapy Infusion Reactions

Vascular Endothelial Growth Factor

Bevacizumab (Avastin) Metastatic CRC,(Breast-but now no longer FDA approved),met.Renal,progressive GBM,NSCLC Antiangiogenic agent Given IV 28 days AFTER a surgical procedure due to poor wound healing Nosebleeds/Hemorrhage Proteinuria Hypertension Infusion Reactions GI Perforation

Prognosis of metastatic CRC has significantly improved with the addition of targeted therapies to new and existing chemotherapy treatments Newer targeted therapies have different side effect than we usually expect-i.e. transfusion related reactions, acneform rash The GI associate can be a pivotal player in getting the appropriate sample sent for testing for the newer targeted agents