As part of your treatment, you may be asked to participate in a clinical trial. These studies are designed to find innovative ways to treat cancer and can involve many different forms of treatment, such as new drugs, new types of surgery or radiation, and very modern methods, such as gene therapy. New drugs are only brought into clinical trials after they have been extensively researched in the laboratory. However, it is only when they are tested in people that we can begin to understand their effectiveness and safety.

Clinical trials help advance the treatment of cancer. Today's standard treatments for cancers of the breast, colon, and those of childhood were tested in this way. The information gained from these trials has helped many patients with cancer live much longer than was possible in the past.

Patients who take part in clinical trials may also benefit from the new form of treatment under study. They receive the most current treatment from cancer experts who will carefully monitor their condition. If the new treatment has a potential advantage, they may be the first to receive it. There is no guarantee that the new treatments will be better and there will likely be unexpected side effects. Alternatively, patients may be offered the standard treatment so that the effectiveness of the new treatment can be accurately judged and compared.

Whether you are invited to participate in a clinical trial will depend on certain factors:

• Is the hospital you attend taking part in a trial for your form of cancer?
• Do you fulfill the entry criteria (eg, are you at the correct stage of the disease or do you have any other conditions that preclude your entry)?

Types of Clinical Trials

Phase I:
These trials are the first stage in testing a new treatment in humans and may include healthy volunteers. Phase I trials determine the metabolism and pharmacologic actions of drugs in humans, assess the side effects associated with increasing doses, and provide early evidence of effectiveness. With cancer drugs, because the risks and benefits of the new drug are very uncertain, only cancer patients for whom other treatments are unlikely to help take part in Phase I trials.

Phase II:
The next stage looks at whether the treatment has a significant anticancer effect. A moderate number of patients take part in these trials, generally 400 patients or less, again because there is still much to learn about the treatment. These trials also look at safety and effectiveness, and are designed to determine the best dose(s) for the drug.

Phase III:
After preliminary evidence suggesting safety and effectiveness of the drug has been obtained, these controlled and uncontrolled trials are designed to provide additional efficacy and safety in patient populations for which the medicine is eventually intended, and to gather additional information to evaluate the overall benefit-risk relationship of the drug and provide an adequate basis for physician labeling. These trials often involve hundreds to thousands of patients from many different hospitals and treatment centers from around the world.

Randomized trials

In these studies, researchers randomly allocate patients to a treatment group by equally distributing people with particular characteristics among all the trial arms. This helps to minimize the differences among groups. For example, if patients with a poorer prognosis were preferentially given the new treatment, then the study results would not appear to be as positive as they actually were.

Double- or single-blind trials

In double-blind trials, neither the patient nor the doctor treating the patient knows which treatment is being given. In single-blind trials, only the patient is unaware of the treatment. These techniques are used because patients and doctors may be unconsciously influenced in the way they judge results by knowing what kind of treatment is being given. It may not be possible to blind some trials (eg, oral versus intravenous therapy, although even here dummy treatments can be given in what's known as a double-dummy trial). Clinical trials in cancer are less frequently blinded than those in other diseases.

 

Nexavar Important Safety Information

Name of the medicinal product: Nexavar^® 200 mg film-coated tablets.

Qualitative and quantitative composition: 200 mg sorafenib (as tosylate)

Indication:

1. Treatment of hepatocellular carcinoma.
2. Treatment of patients with advanced renal cell carcinoma who have failed prior interferon-alpha or interleukin-2 based therapy or are considered unsuitable for such therapy.

Contraindications: Hypersensitivity to sorafenib or to any of the excipients.

Warnings and Precautions: Hand-foot skin reaction and rash, usually CTC grade 1 and 2. Increased incidence of arterial hypertension (usually mild to moderate, early in the course of treatment). Blood pressure should be monitored regularly and treated as appropriate. Increased risk of bleeding. Increased incidence of cardiac ischaemia/infarction. Gastrointestinal perforation in less than 1%; sorafenib to be discontinued. Levels of sorafenib may be increased in patients with severe hepatic impairment. Infrequent bleeding events or elevations in INR have been reported in some patients taking warfarin concomitantly. Patients on such therapy should be monitored. Temporary treatment interruption and/or dose modification or discontinuation may be considered, depending on the severity of the observed adverse reactions. No formal studies on wound healing have been conducted. Temporary interruption of sorafenib therapy is recommended in patients undergoing major surgical procedures. Experience of use in the elderly is limited and cases of renal failure have been reported. High risk patients according to MSKCC prognostic group were not included in the phase III study in renal cell carcinoma and benefit-risk has not been evaluated in these patients. Caution is recommended when administering sorafenib with compounds that are metabolised/eliminated predominantly by the UGT1A1 (e.g. irinotecan) or UGT1A9 pathways. Caution is recommended when sorafenib is co-administered with docetaxel. The risk of reduced plasma concentrations of sorafenib should be considered before starting a treatment course with antibiotics.

Undesirable effects: Very common: lymphopenia, hypophosphataemia, haemorrhage (incl. gastrointestinal, respiratory tract, cerebral), hypertension, diarrhoea, nausea, vomiting, rash, alopecia, hand-foot syndrome (palmar plantar erythrodysaesthesia syndrome), erythema, pruritus, fatigue, pain (mouth, abdominal, bone, tumour, headache), increased amylase and lipase. Common: leucopenia, neutropenia, anaemia, thrombocytopenia, anorexia, depression, peripheral sensory neuropathy, tinnitus, hoarseness, constipation, stomatitis (including dry mouth and glossodynia), dyspepsia, dysphagia, dry skin, dermatitis exfoliative, acne, skin desquamation, arthralgia, myalgia, renal failure, erectile dysfunction, asthenia, fever, influenza like illness, weight decrease, transient increase in transaminases. Uncommon: folliculitis, infection, hypersensitivity reactions (including skin reactions and urticaria), hypothyroidism, hyperthyroidism, hyponatraemia, dehydration, reversible posterior leukoencephalopathy, myocardial ischaemia and infarction, congestive heart failure, hypertensive crisis, rhinorrhea, gastro oesophageal reflux disease, pancreatitis, gastritis, gastrointestinal perforations, increase in bilirubin, jaundice, cholecystitis, cholangitis, eczema, erythema multiforme, keratoacanthoma / squamous cell cancer of the skin, Stevens-Johnson syndrome, gynaecomastia, increase in alkaline phosphatase, INR abnormality, prothrombin level abnormality. On prescription only.

Date of Revision of the Text: July 2009. Please note! For current prescribing information refer to the package insert and /or contact your local Bayer Schering Pharma Organisation. Bayer Schering Pharma AG, 13342 Berlin, Germany.

 

INDICATIONS & USAGE

NEXAVAR is an anticancer medicine used to treat a certain type of liver or kidney cancer called:

• hepatocellular carcinoma (HCC), when it cannot be treated with surgery
• renal cell carcinoma (RCC, a type of kidney cancer).

IMPORTANT SAFETY INFORMATION ABOUT NEXAVAR

NEXAVAR may cause birth defects or death of an unborn baby. Avoid becoming pregnant while taking NEXAVAR and for at least 2 weeks after stopping your treatment. Men and women should use birth control during and at least 2 weeks after NEXAVAR therapy. Call your doctor right away if you become pregnant. Do not breastfeed while taking NEXAVAR as this medication may be passed through breast milk.

Before starting NEXAVAR, tell your doctor if you have: allergies; heart problems or chest pain; bleeding or bruising problems; high blood pressure; or kidney or liver problems. NEXAVAR may interact with certain other medicines so tell your doctor about all medicines you take including prescription and over-the-counter (OTC) medicines, vitamins, or herbal supplements. It is especially important to tell your doctor if you take warfarin (Coumadin).

NEXAVAR may cause serious side effects, including:

• decreased blood flow to the heart and heart attack Get emergency help if you have chest pain, shortness of breath, feel lightheaded or faint, have nausea or vomiting, or you are sweating a lot.
• bleeding problems. Tell your doctor if you have any bleeding or easy bruising while taking NEXAVAR.
• high blood pressure. Your blood pressure should be checked every week during the first 6 weeks of starting therapy and then regularly, thereafter. If your blood pressure is high, it may need to be treated.
• a skin problem called hand-foot skin reaction. This causes redness, pain, swelling or blisters on the palms of your hands and soles of your feet. Your doctor may change your dose or stop treatment for a while.
• perforation of the bowel. Tell your doctor right away if you get high fever, nausea, vomiting or abdominal pain.
• wound healing problems. If you have a surgical or dental procedure, tell your doctor you are taking NEXAVAR. Your treatment may be stopped until after your surgery or until your wound heals.

Other side effects with NEXAVAR can include: rash, redness, itching or peeling skin; hair thinning or loss; diarrhea; nausea/vomiting; mouth sores; weakness; loss of appetite; numbness, tingling or pain in hands and feet; abdominal pain; tiredness; or weight loss. Tell your doctor if you have any side effects that bother you or do not go away.

Please see full Prescribing Information

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.