PATIENT BROCHURE WARNING: ALLERGIC REACTIONS. Metastatic Colorectal Cancer: Indications. Allergic Reactions

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1 PATIENT BROCHURE Metastatic Colorectal Cancer: Indications n ERBITUX is approved for the treatment of certain patients who have colorectal cancer that has spread to other parts of the body. Only patients whose tumors are KRAS wild-type (which means they have a KRAS mutation-negative gene), and whose tumors have a protein called epidermal growth factor receptor (EGFR), should receive ERBITUX. FDA-approved tests are used to determine if tumors have these particular traits. Treatment with ERBITUX is given in the following three ways: In combination with FOLFIRI (irinotecan, -fluorouracil, leucovorin) for patients who are being treated for this type of cancer for the first time In combination with another chemotherapy drug, irinotecan, for patients whose disease has progressed after receiving chemotherapy with irinotecan As a single agent: For patients whose disease has progressed after receiving both irinotecan and oxaliplatin For patients who are unable to tolerate chemotherapy with irinotecan n ERBITUX is not approved to treat colorectal cancer in patients whose tumors have mutations in genes called RAS (often called RAS mutant ), or in patients for whom the mutational status of the genes is not known ERBITUX is available by prescription only. WARNING: ALLERGIC REACTIONS Allergic Reactions n Severe allergic reactions due to ERBITUX (cetuximab) therapy have occurred in of 7 patients (%) receiving ERBITUX during clinical studies, resulting in death in less than in patients Symptoms can include trouble with breathing (including tightening of the airways, wheezing, or hoarseness), low blood pressure, shock, loss of consciousness, and/or heart attack. Report these signs and symptoms of infusion reactions, as well as fever, chills, or breathing problems to your doctor or nurse Approximately 9% of the severe allergic reactions occurred with the first dose of ERBITUX, although some patients experienced their first severe allergic reaction during a subsequent dose of ERBITUX Your doctor or nurse should watch you closely for these symptoms during treatment and may need to stop therapy in the event of an allergic reaction Severe allergic reactions require that treatment with ERBITUX be stopped immediately and not started again Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure.

2 This brochure, along with advice from your doctor, will help guide you and your loved ones through your treatment journey. Inside, you will find ways to: Learn about your diagnosis Understand your treatment better Learn about financial assistance options through Lilly PatientOne Care for certain side effects associated with ERBITUX treatment Learn about a complimentary self-care kit with information and products that may help with skin care What is colorectal cancer? What is metastatic colorectal cancer? 6 What happens after diagnosis? 8 How was ERBITUX shown to work? 9 How will I be given ERBITUX? ERBITUX side effects Tips to care for select side effects Caring for your skin, nails, and hair during treatment Learn about financial assistance options through Lilly PatientOne 6 What does it mean to be a caregiver? 8 Important Safety Information Glossary of common terms Patient Information This brochure can t replace information or advice given by your doctor or nurse. Your healthcare team will tell you more about your condition and treatment plan and answer any questions you may have. Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure.

3 What is colorectal cancer? What is metastatic colorectal cancer? Colorectal cancer is a disease in which cells in the colon or rectum become abnormal and divide uncontrollably, forming a mass called a tumor. The colon is the longest part of the large intestine, and the rectum is the last several inches of the large intestine closest to the anus. The colon and rectum are parts of the body s digestive system, which takes up nutrients from food and water and stores solid waste until it passes out of the body. Transverse Colon When cancer is metastatic, it means that it has spread from the place where it started to other places in the body. No matter where a cancer may spread, it s always named for the place where it started. For example, colorectal cancer that has spread to the lung is called metastatic colorectal cancer, not lung cancer. When colorectal cancer spreads, it spreads most often to the liver. Sometimes it spreads to the lungs, bones, or other organs. Metastatic The cancer has spread from the place where it started to other places in the body. For more definitions, please see page. Ascending Colon Descending Colon Tumor Liver Metastasis Lung Metastasis Bone Metastasis Sigmoid Colon Colon Cancer Original tumor Rectum Could also be site of original tumor Rectum SELECT IMPORTANT SAFETY INFORMATION Lung Disease n Lung disease, which resulted in one death, occurred in of 7 patients (<.%) receiving ERBITUX in several clinical trials in colorectal cancer and head and neck cancer Notify your doctor if you develop shortness of breath while receiving ERBITUX ERBITUX treatment should be stopped if symptoms worsen or lung disease is confirmed Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure.

4 What happens after diagnosis? Tumor marker Also called biomarker. A substance found in tissue, blood, or other body fluids that may be a sign of cancer or certain benign (noncancerous) conditions. KRAS KRAS is a gene found in colorectal cancer cells and some normal cells. Some people with colorectal cancer have a mutated (or altered) KRAS gene. RAS A family of genes, which includes the KRAS gene and the NRAS gene, that may cause cancer when they are mutated or changed. KRAS wild-type A KRAS gene that is not mutated. After your diagnosis, you may have several questions for your care team. To help you understand more about next steps, consider asking: Where is my tumor located? Has the cancer spread? Will I need more tests before we choose a treatment? You and your doctor will work together to decide what the best treatment is for you. This decision will be based on a number of factors, including your health, your preferences, and your KRAS biomarker status (wild-type or mutant). Some common treatment options for colorectal cancer Surgery A procedure or operation to remove or repair a part of the body or to find out whether disease is present. Radiation therapy (also called radiotherapy) Treatment of disease using high-energy waves or streams of particles called radiation. Chemotherapy A certain group of drugs used to treat patients with cancer. Biologic therapy A substance that is made from a living organism or its products used in the prevention, diagnosis, or treatment of cancer and other diseases. Biologic agents include antibodies, interleukins, and vaccines. Ask your doctor if you are eligible for ERBITUX Knowing your KRAS status will help your doctor decide if you are eligible for treatment with ERBITUX. Your doctor will also need to confirm that your tumor does not have mutations, or changes, on a family of genes called RAS, which includes the KRAS gene and NRAS gene. To find out the status of these genes, your doctor will test a sample removed from your tumor. The sample is sent to a lab to be tested for mutations. KRAS wild-type RAS mutant ERBITUX may work when colorectal cancer cells are KRAS wild-type. However, some people with wild-type KRAS still won t respond. ERBITUX is not approved to treat colorectal cancer in patients whose tumors have mutations in genes called RAS (often called RAS mutant ), or in patients for whom the mutational status of the genes is not known. Typically, 6-8 weeks after you start treatment, your doctor may do a CT, PET, or other kind of scan to see whether or not the treatment is working. A scan after treatment enables your doctor to tell you if your tumor disappeared, shrank, stayed the same, or grew. You may continue to have scans taken during and after treatment. Computed tomography (CT) scan Also called a CAT scan, which is a series of detailed pictures of areas inside the body created by a computer linked to an X-ray machine. Positron emission tomography (PET) scan A procedure in which a small amount of radioactive sugar is injected into a vein, and a scanner is used to make pictures of areas inside the body where the sugar can be found. Cancer cells often take up more sugar than normal cells, so a PET scan can be used to find cancer cells in the body. In some cases, treatments may be combined. SELECT IMPORTANT SAFETY INFORMATION Increased Tumor Growth, Increased Death, or Lack of Benefit in Patients with RAS-Mutation Positive or Mutant Colorectal Cancer n You should not be treated with ERBITUX if you have colorectal cancer that has mutations in the RAS genes because you will not benefit from ERBITUX treatment and will experience side effects Tumor size Typically after 6-8 weeks of treatment SCAN Did it disappear? Did it shrink? Did it stay the same? Did it grow? For more definitions, please see page. Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure. 6 7

5 How was ERBITUX shown to work? How will I be given ERBITUX? In laboratory studies, ERBITUX was shown to: Block the signal ERBITUX TUMOR CELL EGFR ERBITUX can block one of the signals that tells a tumor cell to grow by attaching to a structure on the cell called the epidermal growth factor receptor (EGFR). This structure is found on both normal cells and tumor cells. Trigger an immune response IMMUNE CELL ERBITUX TUMOR CELL EGFR ERBITUX can form a bridge between a tumor cell and an immune cell when it is attached to the EGFR on the tumor cell. As a result, the immune cell can begin a response against the tumor cell. FIRST DOSE HOURS LATER DOSES HOUR ERBITUX is given by slow injection, also called an infusion, into a vein. ERBITUX is usually given once a week. Your doctor will decide how many weeks of treatment you will receive. The first dose of ERBITUX takes approximately hours to give. Later doses take about hour. Before you begin treatment with ERBITUX, you may receive medication to help prevent an allergic reaction. If you experience a side effect, your ERBITUX treatment may need to be changed, delayed, or stopped completely. Intravenous (IV) infusion A type of injection in which a medicine is given over time directly into the blood through a vein. For more definitions, please see page. EGFR n EGFR is a receptor that is important for cell growth n EGFR is present on some cancer cells, including colorectal cancer n EGFR is also present on normal cells like skin, nail, or hair follicles Laboratory studies have shown that ERBITUX does not have an effect against tumor samples that do not have EGFR. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call -8-FDA-88. WARNING: ALLERGIC REACTIONS Allergic Reactions n Severe allergic reactions due to ERBITUX (cetuximab) therapy have occurred in of 7 patients (%) receiving ERBITUX during clinical studies, resulting in death in less than in patients Symptoms can include trouble with breathing (including tightening of the airways, wheezing, or hoarseness), low blood pressure, shock, loss of consciousness, and/or heart attack. Report these signs and symptoms of infusion reactions, as well as fever, chills, or breathing problems to your doctor or nurse Approximately 9% of the severe allergic reactions occurred with the first dose of ERBITUX, although some patients experienced their first severe allergic reaction during a subsequent dose of ERBITUX Your doctor or nurse should watch you closely for these symptoms during treatment and may need to stop therapy in the event of an allergic reaction Severe allergic reactions require that treatment with ERBITUX be stopped immediately and not started again Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure. 8 9

6 ERBITUX side effects ERBITUX may cause side effects. Some can be serious and sometimes fatal, so it is very important that you notify your doctor immediately if you develop any symptoms while receiving ERBITUX. If you experience a side effect, your ERBITUX treatment may need to be changed, delayed, or stopped completely. Select side effects Allergic reactions Severe allergic reactions are a serious side effect with ERBITUX. Allergic reactions are rare but may cause death. Tell your doctor or nurse right away if you have trouble breathing, are wheezing or hoarse, or have fever, chills, or a tight feeling in your airways. Symptoms can also include low blood pressure, shock, loss of consciousness, and/or heart attack. Severe allergic reactions can happen at any time during treatment, but they happen most often at the first dose. ERBITUX may cause nail changes. Nail changes during EGFR treatment may: n Look like pus-filled blisters or swollen, red skin around the fingernails or toenails n Cause ingrown nails or infection n Cause nails to form ridges or to fall off n Be swollen and painful n Appear to months after starting treatment n Last for many months after treatment Picture of swollen, discolored fingernail. This image is an example only. Skin problems Skin problems are one of the most serious side effects of ERBITUX. Skin problems include an acne-like rash, skin drying and cracking, infections, and abnormal hair growth. The skin around your fingernails and toenails may swell. Blistering of the skin or mucous membranes (such as the mouth) or peeling of the skin may be symptoms of serious reactions that could lead to death. Contact your doctor right away if you have any of these symptoms. ERBITUX may cause an acne-like skin rash. An acne-like skin rash during EGFR treatment may: n Look like acne, but it is not n Be red, swollen, crusty, and very dry n Feel itchy, tender, painful, or warm or burning (like a sunburn) n Happen on the scalp, face, chest, or upper back, or other parts of the body if the case is severe n Start and may be worse during the first few weeks of treatment n Get better or stay the same during treatment n Go away after treatment is stopped, but not always immediately n Become infected n Cause the skin to change color after the rash has gone away Picture of skin rash on the face. This image is an example only. ERBITUX may cause hair changes. Hair changes during EGFR treatment may: n Make the eyelashes grow very fast and become very long and bother your eyes n Cause fast growth to eyebrows n Cause hair on the scalp to become curly, fine, or brittle n Start a few weeks to months after starting treatment and go away after treatment is stopped Picture of fast-growing eyelashes. This image is an example only. Side effects for each person may vary. Tell your doctor or nurse if you notice any skin, nail, or hair changes, or any other side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call -8-FDA-88. Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure.

7 Tips to care for select side effects Participate in your treatment. Talk to your healthcare provider about your side effects. Tips to help care for skin problems n Talk to your doctor or nurse about management of skin problems n Your doctor or nurse may suggest the use of moisturizing lotion to help keep skin moist n They may also suggest cool compresses to relieve itching n Being out in the sun may make skin problems worse. People receiving ERBITUX should wear sunscreen and hats and limit sun exposure during treatment and for months following the last dose of ERBITUX n Rash may be treated with antibiotics. Antibiotics may be in pill form (and may be taken by mouth) or as a skin cream Tips to help care for diarrhea What to do n Tell your doctor if you experience diarrhea n Eat many small meals, rather than normal-size meals n Eat Bananas, white Rice, Applesauce, white Toast (the BRAT diet) n Drink plenty of water, clear liquids, or sports drinks What to avoid n Do not drink milk or eat milk products, such as ice cream n Do not eat greasy or spicy foods n Avoid whole wheat or whole grain foods and other foods high in fiber, such as raw vegetables, beans, and nuts Tips to help care for fatigue and/or weakness What to do n Tell your doctor if you have fatigue or weakness n Make a plan for each day that includes time for activity and time for rest. Try to do the most important things first, while you have energy n Keep a journal of how you feel each day, noting when you are tired or feeling energetic n Do small amounts of activity to give yourself energy n For persistent fatigue, talk to your doctor What to avoid n Avoid foods or drinks with caffeine, such as coffee or chocolate, in the afternoon or night n If you are having trouble sleeping at night, avoid late-afternoon naps Tips to help care for nausea n Tell your doctor if you have nausea n Eat smaller meals more often during the day n Eat foods that are light or bland (have a mild flavor), such as chicken noodle soup or scrambled eggs n Eat dry foods, such as crackers, bread, or dry cereal, when you first wake up or if your stomach is empty n Sip clear liquids, such as water or a sports drink, or suck on ice chips or ice pops n Rest a bit after eating, but avoid lying down flat for at least hour after a meal n Rinse your mouth before and after you eat a meal You may experience other side effects while being treated with ERBITUX. Your treatment team is there to help, so be sure to let them know about any side effects that are bothering you. Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure.

8 Caring for your skin, nails, and hair during treatment Get your complimentary self-care kit The self-care kit contains information on the possible side effects of EGFR inhibitors, such as ERBITUX, as well as products and suggestions to help with skin care. Using the tips and materials in the self-care kit may help manage side effects. If you have any questions, please be sure to discuss them with your treatment team. Talk to your doctor to determine if the self-care kit is right for you. Advice n A brochure with information about potential skin, nail, and hair changes n Helpful tips The self-care kit includes Care products n Lotions n Sunscreen n Gentle bathing products n Nail care kit Lilly PatientOne may help with the costs of your prescribed Lilly Oncology medications Find easy-to-use forms and reimbursement information to help support your patient s treatment journey. Lilly PatientOne is committed to helping eligible patients access support programs for Lilly Oncology products they are prescribed. We aim to address both financial and coverage issues for qualified uninsured, underinsured, and insured patients. Lilly PatientOne strives to offer resources, ranging from benefits investigations to financial assistance and appeals information, that provide reliable and individualized treatment support for eligible patients. Ask your doctor or visit ERBITUX.com for more information about the self-care kit. For more information about Lilly PatientOne, call -866-PatOne ( ), Monday Friday, 9 am 7 pm ET, or visit LillyPatientOne.com. Caregiver Information Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure.

9 What does it mean to be a caregiver? After cancer is diagnosed, the person you love will face a challenging journey. As a caregiver, you will share that journey and become a source of comfort and support. As a caregiver, you are going to help your loved one with everyday tasks. These can include: n Preparing food n Helping with things around the house n Taking them to the doctor Your most important role as a caregiver is providing emotional and spiritual support for your loved one. It is also important to be there to help them cope with their cancer and provide support through their treatment. As a caregiver, it s important to take care of yourself, too While caring for your loved one, you may feel as if you don t have time to take care of yourself. After a while your emotional and physical well-being may suffer. Taking care of yourself will help you take better care of your loved one. Make time for yourself every day. Tips to help maintain your health n Eating well will help you keep up your strength n Get plenty of rest to stay energized during the day n Exercise is a great way to keep your body healthy and mind clear n Learn how to relax to help relieve stress You can get support You re not alone, but sometimes when looking after your loved one it may feel that way. This can cause increased levels of stress, feelings of being overwhelmed, and even physical sickness. Remember, there is nothing wrong with asking for help. ways to help care for yourself n Find comfort in things you enjoy doing n Look for positives to bring your spirits up n Find acceptance and vow to live each day to its fullest n Feel thankful that you can be there for your loved one To find support, contact: Caregiver Action Network n Connect with other people so you won t get overwhelmed n Let yourself laugh to release tension n Write in a journal to relieve negative thoughts n Confront your anger and try to defuse it the moment it happens n Let go of your guilt to help you focus on what you need to do n Join a support group so you know you re not alone If the responsibility of caring for your loved one is causing you to experience signs of fatigue, weight loss or weight gain, changes in appetite, headaches, or mood swings, be sure to speak with your physician. Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure. 6 7

10 IMPORTANT SAFETY INFORMATION WARNING: ALLERGIC REACTIONS Allergic Reactions n Severe allergic reactions due to ERBITUX (cetuximab) therapy have occurred in of 7 patients (%) receiving ERBITUX during clinical studies, resulting in death in less than in patients Symptoms can include trouble with breathing (including tightening of the airways, wheezing, or hoarseness), low blood pressure, shock, loss of consciousness, and/or heart attack. Report these signs and symptoms of infusion reactions, as well as fever, chills, or breathing problems to your doctor or nurse Approximately 9% of the severe allergic reactions occurred with the first dose of ERBITUX, although some patients experienced their first severe allergic reaction during a subsequent dose of ERBITUX Your doctor or nurse should watch you closely for these symptoms during treatment and may need to stop therapy in the event of an allergic reaction Severe allergic reactions require that treatment with ERBITUX be stopped immediately and not started again Lung Disease n Lung disease, which resulted in one death, occurred in of 7 patients (<.%) receiving ERBITUX in several clinical trials in colorectal cancer and head and neck cancer Notify your doctor if you develop shortness of breath while receiving ERBITUX ERBITUX treatment should be stopped if symptoms worsen or lung disease is confirmed Skin Problems n In several clinical trials in colorectal cancer and head and neck cancer with ERBITUX, skin problems including an acne-like rash, skin drying and cracking, infections (including infections of the blood, skin, eyes, and lips), and abnormal hair growth were seen Sun exposure may worsen these effects Patients taking ERBITUX should wear sunscreen and hats to limit sun exposure while receiving and for months following the last dose of ERBITUX Severe reactions with symptoms of rash; blistering of the skin, mouth, eyes, and genitals; and shedding of the skin have been seen in patients treated with ERBITUX. These reactions may be life-threatening and possibly lead to death. It is not clear if these reactions are related to the way ERBITUX works or to an immune response, such as Stevens-Johnson syndrome or toxic epidermal necrolysis A related nail disorder that causes painful swelling of the skin around the nails most often of the large toes and thumbs also was reported Notify your doctor if you develop any of these symptoms while receiving ERBITUX Electrolyte Depletion n Low levels of magnesium and accompanying low calcium and potassium levels have been reported with ERBITUX when given by itself and in combination with other cancer drugs Your doctor or nurse should periodically monitor your blood electrolyte levels and administer intravenous replacement as needed Increased Tumor Growth, Increased Death, or Lack of Benefit in Patients with RAS-Mutation Positive or Mutant Colorectal Cancer n You should not be treated with ERBITUX if you have colorectal cancer that has mutations in the RAS genes because you will not benefit from ERBITUX treatment and will experience side effects Pregnancy and Nursing n Notify your doctor if you are pregnant or if you become pregnant while receiving ERBITUX. Contraception must be used, in both males and females, during ERBITUX therapy and for 6 months following the last dose of ERBITUX. ERBITUX may be passed from the mother to the developing fetus, and may cause harm to the fetus. ERBITUX should only be used during pregnancy if the potential benefit is greater than the potential risk to the fetus n ERBITUX may be passed through human breast milk. Because of the potential for serious side effects in nursing infants from ERBITUX, nursing is not recommended during ERBITUX therapy and for two months following the last dose of ERBITUX Additional Side Effects In studies of ERBITUX: n The most serious side effects associated with ERBITUX in colorectal cancer that had spread to other parts of the body are: allergic reactions, skin problems, infection, kidney failure, lung disease, and blood clots in the lung n The most frequent side effects associated with ERBITUX (reported in at least % of patients) are skin problems (including rash, itching, and nail changes), headache, diarrhea, and infection In a study of European cetuximab in combination with FOLFIRI (irinotecan, -fluorouracil, leucovorin) given to 7 patients versus FOLFIRI alone given to patients with colorectal cancer that had spread to other parts of the body whose tumors were KRAS wild-type and whose tumors had a protein called Epidermal Growth Factor Receptor (EGFR): n The most frequent side effects were: acne-like rash (86% versus %) and diarrhea (66% versus 6%) n Serious side effects reported by at least % of patients in either arm were: abnormal decrease in white blood cell count (% versus %), acne-like rash (8% versus <%), and diarrhea (6% versus %) n ERBITUX yields approximately % higher blood levels of cetuximab relative to European cetuximab. In this study, the side effects and severity of adverse reactions seen with European cetuximab were consistent with other studies of U.S. patients receiving ERBITUX for metastatic colorectal cancer Please see Important Safety Information continued on the next page and full Prescribing Information for ERBITUX, including Boxed Warning regarding allergic reactions, included at the end of this brochure. 8 9

11 IMPORTANT SAFETY INFORMATION (CONTINUED) In a study where ERBITUX and supportive care were given to 8 patients versus supportive care which was given to patients with colorectal cancer that had spread to other parts of the body whose tumors were KRAS wild-type and whose tumors had a protein called Epidermal Growth Factor Receptor (EGFR): n The most frequent side effects reported were: rash or shedding of the outer layer of the skin (9% versus %), feeling tired (9% versus 79%), nausea (6% versus %), dry skin (7% versus %), other pain (9% versus 7%), and constipation (% versus 8%) n Serious side effects reported by at least % of patients included: fatigue (% versus 9%), other pain (8% versus %), rash or shedding of the outer layer of the skin (6% versus %), shortness of breath (6% versus %), other intestinal problems (% versus %) and infection without abnormal decrease in white blood cell count (% versus %) In studies where ERBITUX and irinotecan were given to patients with colorectal cancer that had spread to other parts of the body whose tumors had a protein called Epidermal Growth Factor Receptor (EGFR): n The most frequent side effects reported were: acne-like rash (88%), feeling weakness or discomfort (7%), diarrhea (7%), and nausea (%) n Serious side effects reported by at least % of patients included: diarrhea (%), decrease in white blood cell count (7%), feeling weakness or discomfort (6%), and acne-like rash (%) You are encouraged to report negative side effects of Prescription drugs to the FDA. Visit or call -8-FDA-88. Please see full Prescribing Information for ERBITUX, including Boxed Warning for allergic reactions, included at the end of this brochure. CE CON ISI_CRC 7JUN Glossary of common terms Allergic reaction: A reaction that happens when a person comes in contact with a substance to which that person is especially sensitive. Cell: The individual unit that makes up the tissues of the body. Computed tomography (CT) scan: Also called a CAT scan, which is a series of detailed pictures of areas inside the body created by a computer linked to an X-ray machine. Diagnosis: The process of identifying a disease, such as cancer, from its signs and symptoms. A health history, physical exam, and tests may be used to make a diagnosis. EGFR: A receptor found on both normal and tumor cells that is important for cell growth. Intravenous (IV) infusion: A type of injection in which a medicine is given over time directly into the blood through a vein. KRAS: KRAS is a gene found in colorectal cancer cells and some normal cells. Some people with colorectal cancer have a mutated (or altered) KRAS gene. KRAS wild-type: A KRAS gene that is not mutated. Metastatic: The cancer has spread from the place where it started to other places in the body. Positron emission tomography (PET) scan: A procedure in which a small amount of radioactive sugar is injected into a vein, and a scanner is used to make pictures of areas inside the body where the sugar can be found. Cancer cells often take up more sugar than normal cells, so a PET scan can be used to find cancer cells in the body. RAS: A family of genes, which includes the KRAS gene and the NRAS gene, that may cause cancer when they are mutated or changed. RAS mutant: A RAS gene that is changed. Scan: A picture of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. Side effect: A problem that occurs when treatment affects healthy tissues or organs. Tumor: An abnormal mass of tissue that forms when cells grow and divide uncontrollably. A tumor may be either benign (not cancerous) or malignant (cancerous). Tumor marker: Also called biomarker. A substance found in tissue, blood, or other body fluids that may be a sign of cancer or certain benign (noncancerous) conditions.

12 Get involved: Educate yourself Educating yourself whether it s your diagnosis or a loved one s is an important step, regardless of whether you re newly diagnosed or have been living with metastatic colorectal cancer for a while. There are many outside resources you can turn to, whether you want to learn more about your cancer or you re looking for support from other people who are going through the same thing. Websites you may find helpful SUPPORT Association of Cancer Online Resources --6- n CancerCare -8-8-HOPE ( ) Cancer Information Service -8--CANCER (-8--67) Cancer Support Community LIVESTRONG n CAREGIVER SUPPORT Caregiver Action Network n COLORECTAL CANCER ChrisLife Colon Cancer Foundation n Colon Cancer Alliance n Fight Colorectal Cancer n Michael s Mission info@michaelsmission.org EDUCATION American Cancer Society n National Cancer Institute -8--CANCER (-8--67) National Comprehensive Cancer Network n Prevent Cancer Foundation n ADVOCACY National Coalition for Cancer Survivorship -877-NCCS-YES ( ) Patient Advocate Foundation n Other product or company names mentioned herein are the trademarks of their respective owners. When you contact any of the third parties listed in this brochure, please note that each one is solely responsible for its own content. Lilly USA, LLC, does not control, influence, or endorse these resources, and the opinions, claims, or comments expressed by them should not be attributed to Lilly USA, LLC. Lilly USA, LLC, is not responsible for the privacy policy of any third-party websites. We encourage you to read the privacy policy of every website you visit. Please see Important Safety Information, including Boxed Warning regarding allergic reactions, on pages 8- and full Prescribing Information included at the end of this brochure. PP-CE-US- /7 Lilly USA, LLC 7. All rights reserved. ERBITUX is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.

13 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ERBITUX safely and effectively. See full prescribing information for ERBITUX. ERBITUX (cetuximab) injection, for intravenous infusion Initial U.S. Approval: WARNING: SERIOUS INFUSION REACTIONS and CARDIOPULMONARY ARREST See full prescribing information for complete boxed warning. Serious infusion reactions, some fatal, occurred in approximately % of patients. (.) Cardiopulmonary arrest and/or sudden death occurred in % of patients with squamous cell carcinoma of the head and neck treated with Erbitux and radiation therapy and in % of patients with squamous cell carcinoma of the head and neck treated with cetuximab in combination with platinum-based therapy with -fluorouracil (-FU). Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after Erbitux administration. (.,.6) INDICATIONS AND USAGE Erbitux is an epidermal growth factor receptor (EGFR) antagonist indicated for treatment of: Head and Neck Cancer Locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. (.,.) Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with -FU. (.,.) Recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy. (.,.) Colorectal Cancer K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by FDA-approved tests in combination with FOLFIRI for first-line treatment, in combination with irinotecan in patients who are refractory to irinotecanbased chemotherapy, as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan. (.,.7,.,.) Limitation of Use: Erbitux is not indicated for treatment of Ras-mutant colorectal cancer. (.7,.) DOSAGE AND ADMINISTRATION Premedicate with an H antagonist. (.) Administer mg/m initial dose as a -minute intravenous infusion followed by mg/m weekly infused over 6 minutes. (.,.) FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: SERIOUS INFUSION REACTIONS AND CARDIOPULMONARY ARREST INDICATIONS AND USAGE. Squamous Cell Carcinoma of the Head and Neck (SCCHN). K-Ras Wild-type, EGFR-expressing Colorectal Cancer DOSAGE AND ADMINISTRATION. Squamous Cell Carcinoma of the Head and Neck. Colorectal Cancer. Recommended Premedication. Dose Modifications. Preparation for Administration DOSAGE FORMS AND STRENGTHS CONTRAINDICATIONS WARNINGS AND PRECAUTIONS. Infusion Reactions. Cardiopulmonary Arrest. Pulmonary Toxicity. Dermatologic Toxicity. Use of Erbitux in Combination With Radiation and Cisplatin.6 Hypomagnesemia and Electrolyte Abnormalities.7 Increased Tumor Progression, Increased Mortality, or Lack of Benefit in Patients with Ras-Mutant mcrc.8 Epidermal Growth Factor Receptor (EGFR) Expression and Response ERBITUX (cetuximab) injection, for intravenous infusion ERB--USPI-6 Initiate Erbitux one week prior to initiation of radiation therapy. Complete Erbitux administration hour prior to platinum-based therapy with -FU (.) and FOLFIRI (.). Reduce the infusion rate by % for NCI CTC Grade or infusion reactions and non-serious NCI CTC Grade infusion reaction. (.) Permanently discontinue for serious infusion reactions. (.) Withhold infusion for severe, persistent acneiform rash. Reduce dose for recurrent, severe rash. (.) DOSAGE FORMS AND STRENGTHS mg/ ml, single-use vial () mg/ ml, single-use vial () CONTRAINDICATIONS None. () WARNINGS AND PRECAUTIONS Infusion Reactions: Immediately stop and permanently discontinue Erbitux for serious infusion reactions. Monitor patients following infusion. (.) Cardiopulmonary Arrest: Closely monitor serum electrolytes during and after Erbitux. (.,.6) Pulmonary Toxicity: Interrupt therapy for acute onset or worsening of pulmonary symptoms. (.) Dermatologic Toxicity: Mucocutaneous adverse reactions. Limit sun exposure. Monitor for inflammatory or infectious sequelae. (.,.) Hypomagnesemia: Periodically monitor during and for at least 8 weeks following the completion of Erbitux. Replete electrolytes as necessary. (.6) Increased tumor progression, increased mortality, or lack of benefit in patients with Ras-mutant mcrc. (.7) ADVERSE REACTIONS The most common adverse reactions (incidence %) are: cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, diarrhea, and infection. (6) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at -8-LillyRx ( ) or FDA at -8-FDA-88 or USE IN SPECIFIC POPULATIONS Pregnancy: Administer Erbitux to a pregnant woman only if the potential benefit justifies the potential risk to the fetus. (8.) Nursing Mothers: Discontinue nursing during and for 6 days following treatment with Erbitux. (8.) See 7 for PATIENT COUNSELING INFORMATION. ERBITUX (cetuximab) injection, for intravenous infusion Revised: /6 6 ADVERSE REACTIONS 6. Clinical Trials Experience 6. Immunogenicity 6. Postmarketing Experience 8 USE IN SPECIFIC POPULATIONS 8. Pregnancy 8. Nursing Mothers 8. Pediatric Use 8. Geriatric Use OVERDOSAGE DESCRIPTION CLINICAL PHARMACOLOGY. Mechanism of Action. Pharmacodynamics. Pharmacokinetics NONCLINICAL TOXICOLOGY. Carcinogenesis, Mutagenesis, Impairment of Fertility. Animal Pharmacology and/or Toxicology CLINICAL STUDIES. Squamous Cell Carcinoma of the Head and Neck (SCCHN). Colorectal Cancer 6 HOW SUPPLIED/STORAGE AND HANDLING 7 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are not listed. ERB--USPI-6

14 FULL PRESCRIBING INFORMATION WARNING: SERIOUS INFUSION REACTIONS and CARDIOPULMONARY ARREST Infusion Reactions: Serious infusion reactions occurred with the administration of Erbitux in approximately % of patients in clinical trials, with fatal outcome reported in less than in. [See Warnings and Precautions (.), Adverse Reactions (6).] Immediately interrupt and permanently discontinue Erbitux infusion for serious infusion reactions. [See Dosage and Administration (.), Warnings and Precautions (.).] Cardiopulmonary Arrest: Cardiopulmonary arrest and/or sudden death occurred in % of patients with squamous cell carcinoma of the head and neck treated with Erbitux and radiation therapy in Study and in % of patients with squamous cell carcinoma of the head and neck treated with European Union (EU)-approved cetuximab in combination with platinum-based therapy with -fluorouracil (-FU) in Study. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after Erbitux administration. [See Warnings and Precautions (.,.6), Clinical Studies (.).] INDICATIONS AND USAGE. Squamous Cell Carcinoma of the Head and Neck (SCCHN) Erbitux is indicated in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. [See Clinical Studies (.).] Erbitux is indicated in combination with platinum-based therapy with -FU for the first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck. [See Clinical Studies (.).] Erbitux, as a single agent, is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed. [See Clinical Studies (.).]. K-Ras Wild-type, EGFR-expressing Colorectal Cancer Erbitux is indicated for the treatment of K-Ras wild-type, epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer (mcrc) as determined by FDA-approved tests for this use [see Dosage and Administration (.), Warnings and Precautions (.7), Clinical Studies (.)]: in combination with FOLFIRI (irinotecan, -fluorouracil, leucovorin) for first-line treatment, in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy, as a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan. [See Warnings and Precautions (.7), Clinical Pharmacology (.), Clinical Studies (.).] Limitation of Use: Erbitux is not indicated for treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown [see Warnings and Precautions (.7), Clinical Studies (.)]. DOSAGE AND ADMINISTRATION. Squamous Cell Carcinoma of the Head and Neck Erbitux in combination with radiation therapy or in combination with platinum-based therapy with -FU: The recommended initial dose is mg/m administered one week prior to initiation of a course of radiation therapy or on the day of initiation of platinum-based therapy with -FU as a -minute intravenous infusion (maximum infusion rate mg/min). Complete Erbitux administration hour prior to platinum-based therapy with -FU. The recommended subsequent weekly dose (all other infusions) is mg/m infused over 6 minutes (maximum infusion rate mg/min) for the duration of radiation therapy (6 7 weeks) or until disease progression or unacceptable toxicity when administered in combination with platinum-based therapy with -FU. Complete Erbitux administration hour prior to radiation therapy or platinum-based therapy with -FU. Erbitux monotherapy: The recommended initial dose is mg/m administered as a -minute intravenous infusion (maximum infusion rate mg/min). The recommended subsequent weekly dose (all other infusions) is mg/m infused over 6 minutes (maximum infusion rate mg/min) until disease progression or unacceptable toxicity.. Colorectal Cancer Determine EGFR-expression status using FDA-approved tests prior to initiating treatment. Also confirm the absence of a Ras mutation prior to initiation of treatment with Erbitux. Information on FDA-approved tests for the detection of K-Ras mutations in patients with metastatic colorectal cancer is available at: invitrodiagnostics/ucm.htm. The recommended initial dose, either as monotherapy or in combination with irinotecan or FOLFIRI (irinotecan, -fluorouracil, leucovorin), is mg/m administered as a -minute intravenous infusion (maximum infusion rate mg/min). Complete Erbitux administration hour prior to FOLFIRI. The recommended subsequent weekly dose, either as monotherapy or in combination with irinotecan or FOLFIRI, is mg/m infused over 6 minutes (maximum infusion rate mg/min) until disease progression or unacceptable toxicity. Complete Erbitux administration hour prior to FOLFIRI.. Recommended Premedication Premedicate with an H antagonist (eg, mg of diphenhydramine) intravenously 6 minutes prior to the first dose; premedication should be administered for subsequent Erbitux doses based upon clinical judgment and presence/severity of prior infusion reactions.. Dose Modifications Infusion Reactions Reduce the infusion rate by % for NCI CTC Grade or and non-serious NCI CTC Grade infusion reaction. Immediately and permanently discontinue Erbitux for serious infusion reactions, requiring medical intervention and/or hospitalization. [See Warnings and Precautions (.).] Dermatologic Toxicity Recommended dose modifications for severe (NCI CTC Grade or ) acneiform rash are specified in Table. [See Warnings and Precautions (.).] Table : Erbitux Dose Modification Guidelines for Rash Severe Acneiform Rash Erbitux Outcome st occurrence Delay infusion to weeks Improvement No Improvement nd occurrence Delay infusion to weeks Improvement No Improvement rd occurrence Delay infusion to weeks Improvement No Improvement th occurrence Discontinue Erbitux Erbitux Dose Modification Continue at mg/m Discontinue Erbitux Reduce dose to mg/m Discontinue Erbitux Reduce dose to mg/m Discontinue Erbitux. Preparation for Administration Do not administer Erbitux as an intravenous push or bolus. Administer via infusion pump or syringe pump. Do not exceed an infusion rate of mg/min. Administer through a low protein binding.-micrometer in-line filter. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless and may contain a small amount of easily visible, white, amorphous, cetuximab particulates. Do not shake or dilute. DOSAGE FORMS AND STRENGTHS mg/ ml, single-use vial mg/ ml, single-use vial CONTRAINDICATIONS None. WARNINGS AND PRECAUTIONS. Infusion Reactions Serious infusion reactions, requiring medical intervention and immediate, permanent discontinuation of Erbitux included rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), hypotension, shock, loss of consciousness, myocardial infarction, and/or cardiac arrest. Severe (NCI CTC and ) infusion reactions occurred in % of 7 patients in Studies,,, and 6 receiving Erbitux, with fatal outcome in patient. [See Clinical Studies (.,.).] Approximately 9% of severe infusion reactions occurred with the first infusion despite premedication with antihistamines. Monitor patients for hour following Erbitux infusions in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (eg, epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen). Monitor longer to confirm resolution of the event in patients requiring treatment for infusion reactions. Immediately and permanently discontinue Erbitux in patients with serious infusion reactions. [See Boxed Warning, Dosage and Administration (.).]. Cardiopulmonary Arrest Cardiopulmonary arrest and/or sudden death occurred in (%) of 8 patients treated with radiation therapy and Erbitux as compared to none of patients treated with radiation therapy alone in Study. Three patients with prior history of coronary artery disease died at home, with myocardial infarction as the presumed cause of death. One of these patients had arrhythmia and one had congestive heart failure. Death occurred 7,, and days after the last dose of Erbitux. One patient with no prior history of coronary artery disease died one day after the last dose of Erbitux. In Study, fatal cardiac disorders and/or sudden death occurred in 7 (%) of 9 patients treated with EU-approved cetuximab and platinum-based therapy with -FU as compared to (%) of patients treated with chemotherapy alone. Five of these 7 patients in the chemotherapy plus cetuximab arm received concomitant cisplatin and patients received concomitant carboplatin. All patients in the chemotherapy-alone arm received cisplatin. Carefully consider use of Erbitux in combination with radiation therapy or platinum-based therapy with -FU in head and neck cancer patients with a history of coronary artery disease, congestive heart failure, or arrhythmias in light of these risks. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after Erbitux. [See Boxed Warning, Warnings and Precautions (.6).] ERBITUX (cetuximab) injection, for intravenous infusion ERB--USPI-6 ERBITUX (cetuximab) injection, for intravenous infusion ERB--USPI-6

15 . Pulmonary Toxicity Interstitial lung disease (ILD), including fatality, occurred in of 7 (<.%) patients receiving Erbitux in Studies,, and 6, as well as other studies, in colorectal cancer and head and neck cancer. Interrupt Erbitux for acute onset or worsening of pulmonary symptoms. Permanently discontinue Erbitux for confirmed ILD.. Dermatologic Toxicity Dermatologic toxicities, including acneiform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae (for example, S. aureus sepsis, abscess formation, cellulitis, blepharitis, conjunctivitis, keratitis/ulcerative keratitis with decreased visual acuity, cheilitis), and hypertrichosis occurred in patients receiving Erbitux therapy. Acneiform rash occurred in 76 88% of 7 patients receiving Erbitux in Studies,,, and 6. Severe acneiform rash occurred in 7% of patients. Acneiform rash usually developed within the first two weeks of therapy and resolved in a majority of the patients after cessation of treatment, although in nearly half, the event continued beyond 8 days. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Erbitux. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (eg, Stevens-Johnson syndrome or toxic epidermal necrolysis). Monitor patients receiving Erbitux for dermatologic toxicities and infectious sequelae. Instruct patients to limit sun exposure during Erbitux therapy. [See Dosage and Administration (.).]. Use of Erbitux in Combination With Radiation and Cisplatin In a controlled study, 9 patients with locally advanced SCCHN were randomized : to receive either Erbitux in combination with radiation therapy and cisplatin or radiation therapy and cisplatin alone. The addition of Erbitux resulted in an increase in the incidence of Grade mucositis, radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances compared to radiation and cisplatin alone. Adverse reactions with fatal outcome were reported in patients (.%) in the Erbitux combination arm and patients (.%) in the control arm. Nine patients in the Erbitux arm (.%) experienced myocardial ischemia compared to patients (.9%) in the control arm. The main efficacy outcome of the study was progression-free survival (PFS). The addition of Erbitux to radiation and cisplatin did not improve PFS..6 Hypomagnesemia and Electrolyte Abnormalities In patients evaluated during clinical trials, hypomagnesemia occurred in % of 6 patients receiving Erbitux in Study and two other clinical trials in colorectal cancer and head and neck cancer, respectively, and was severe (NCI CTC and ) in 6 7%. In Study, where EU-approved cetuximab was administered in combination with platinum-based therapy, the addition of cetuximab to cisplatin and -FU resulted in an increased incidence of hypomagnesemia (% vs. 6%) and of Grade hypomagnesemia (7% vs. %) compared to cisplatin and -FU alone. In contrast, the incidences of hypomagnesemia were similar for those who received cetuximab, carboplatin, and -FU compared to carboplatin and -FU (% vs. %). No patient experienced Grade hypomagnesemia in either arm in the carboplatin subgroup. The onset of hypomagnesemia and accompanying electrolyte abnormalities occurred days to months after initiation of Erbitux. Periodically monitor patients for hypomagnesemia, hypocalcemia, and hypokalemia, during and for at least 8 weeks following the completion of Erbitux. Replete electrolytes as necessary..7 Increased Tumor Progression, Increased Mortality, or Lack of Benefit in Patients with Ras-Mutant mcrc Erbitux is not indicated for the treatment of patients with colorectal cancer that harbor somatic mutations in exon (codons and ), exon (codons 9 and 6), and exon (codons 7 and 6) of either K-Ras or N-Ras and hereafter is referred to as Ras. Retrospective subset analyses of Ras-mutant and wild-type populations across several randomized clinical trials including Study were conducted to investigate the role of Ras mutations on the clinical effects of anti-egfr-directed monoclonal antibodies. Use of cetuximab in patients with Ras mutations resulted in no clinical benefit with treatment related toxicity. [See Indications and Usage (.), Clinical Pharmacology (.), Clinical Studies (.).].8 Epidermal Growth Factor Receptor (EGFR) Expression and Response Because expression of EGFR has been detected in nearly all SCCHN tumor specimens, patients enrolled in the head and neck cancer clinical studies were not required to have immunohistochemical evidence of EGFR tumor expression prior to study entry. Patients enrolled in the colorectal cancer clinical studies were required to have immunohistochemical evidence of EGFR tumor expression. Primary tumor or tumor from a metastatic site was tested with the DakoCytomation EGFR pharmdx test kit. Specimens were scored based on the percentage of cells expressing EGFR and intensity (barely/faint, weak-to-moderate, and strong). Response rate did not correlate with either the percentage of positive cells or the intensity of EGFR expression. 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label: Infusion reactions [See Boxed Warning, Warnings and Precautions (.).] Cardiopulmonary arrest [See Boxed Warning, Warnings and Precautions (.).] Pulmonary toxicity [See Warnings and Precautions (.).] Dermatologic toxicity [See Warnings and Precautions (.).] Hypomagnesemia and Electrolyte Abnormalities [See Warnings and Precautions (.6).] The most common adverse reactions in Erbitux clinical trials (incidence %) include cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, diarrhea, and infection. The most serious adverse reactions with Erbitux are infusion reactions, cardiopulmonary arrest, dermatologic toxicity and radiation dermatitis, sepsis, renal failure, interstitial lung disease, and pulmonary embolus. Across Studies,,, and 6, Erbitux was discontinued in % of patients because of adverse reactions. 6. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data below reflect exposure to Erbitux in 7 patients with SCCHN or colorectal cancer in randomized Phase (Studies and ) or Phase (Studies and 6) trials treated at the recommended dose and schedule for medians of 7 to weeks. [See Clinical Studies ().] Infusion reactions: Infusion reactions, which included pyrexia, chills, rigors, dyspnea, bronchospasm, angioedema, urticaria, hypertension, and hypotension occurred in % of patients across studies. and infusion reactions occurred in % of patients; infusion reactions were fatal in patient. Infections: The incidence of infection was variable across studies, ranging from %. Sepsis occurred in % of patients. Renal: Renal failure occurred in % of patients with colorectal cancer. Squamous Cell Carcinoma of the Head and Neck Erbitux in Combination with Radiation Therapy Table contains selected adverse reactions in patients receiving radiation therapy either alone or with Erbitux for locally or regionally advanced SCCHN in Study. Erbitux was administered at the recommended dose and schedule ( mg/m initial dose, followed by mg/m weekly). Patients received a median of 8 infusions (range ). ERBITUX (cetuximab) injection, for intravenous infusion ERB--USPI-6 ERBITUX (cetuximab) injection, for intravenous infusion ERB--USPI-6 Table : Body System Preferred Term Body as a Whole Asthenia Fever a Headache Infusion Reaction b Infection Chills a Digestive Nausea Emesis Diarrhea Dyspepsia Metabolic/Nutritional Weight Loss Dehydration Alanine Transaminase, high c Aspartate Transaminase, high c Alkaline Phosphatase, high c Respiratory Pharyngitis Skin/Appendages Acneiform Rash d Radiation Dermatitis Application Site Reaction Pruritus a b Incidence of Selected Adverse Reactions ( %) in Patients with Locoregionally Advanced SCCHN Erbitux plus Radiation (n=8) and < 6 < 7 % of Patients Radiation Therapy Alone (n=) and Includes cases also reported as infusion reaction. Infusion reaction is defined as any event described at any time during the clinical study as allergic reaction or anaphylactoid reaction, or any event occurring on the first day of dosing described as allergic reaction, anaphylactoid reaction, fever, chills, chills and fever, or dyspnea. c Based on laboratory measurements, not on reported adverse reactions, the number of subjects with tested samples varied from 6 for Erbitux plus Radiation arm; 9 for Radiation alone. d Acneiform rash is defined as any event described as acne, rash, maculopapular rash, pustular rash, dry skin, or exfoliative dermatitis. The incidence and severity of mucositis, stomatitis, and xerostomia were similar in both arms of the study. < 7 8 8