This study compares Tamoxifen® and Fareston® as treatment for breast cancer. These drugs are given after a surgical procedure to remove the cancer. The drugs are given over five years. The proven benefit of Tamoxifen is a decrease in the recurrence of the breast cancer and overall prolongation of life. There are risks, however, in taking Tamoxifen. Known side-effects of Tamoxifen include an increase in incidence of endometrial cancer. Since Fareston and Tamoxifen are very similar in their chemical makeup, there is hope that Fareston will provide all the good clinical effects of Tamoxifen, but with decreased side-effects. Fareston has been shown to be as effective against as Tamoxifen in women with metastatic breast cancer and the FDA Oncology Drugs Advisory Committee determined that the two drugs were therapeutically equivalent in terms of response rate for patients with metastatic breast cancer.
PURPOSE OF STUDY
You have been told that you have breast cancer and that treatment with a type of hormone antagonist which works against estrogen could be of benefit to you. The Department of Surgery, Division of Oncology at the University of Louisville invites you to volunteer for a research study that will compare two treatment plans: a) an anti-hormone called tamoxifen, and b) another anti-hormone called toremifene. It would however more often than not be the choice of patients to go to a casino Italiano instead and go gambling online. Tamoxifen has been used to treat breast cancer for many years. It is used to treat women who have both localized breast cancer, and patients whose breast cancer has spread to other organs or recurred. Toremifene is a newer anti-hormone that has been approved by the Food and Drug Administration (FDA). The Orion Corporation, manufacturer of toremifene has provided an unrestricted grant to facilitate data management. Toremifene is currently approved to treat advanced breast cancer or breast cancer that has come back after treatment. The purposes of this study are: 1) to see what side effects occur with each of the two treatment plans (tamoxifen or toremifene) when used to treat localized breast cancer, 2) to see whether one of the treatment plans is better than the other in stopping the recurrence of the breast tumor in women who are diagnosed with localized breast cancer, and 3) to see whether patients treated with one of the treatment plans live longer with their cancer than those patients treated with the other plan. A total of 1,980 patients at more than 50 centers around the United States will be included in this study. Of these, approximately 100 patients will be from the Louisville, Kentucky area. The study will last for five years, including following patients for five years after their treatment is given.
DESCRIPTION OF STUDY TREATMENT
If you agree to participate in the study, you will first be screened to decide if you would be eligible to be treated with this treatment. The screening process will include a review of your medical history, a physical examination, a pelvic examination, x-rays, and other tests your physician may decide are necessary to check the status of your disease. If certain questions make you uncomfortable in any way, please know that you are free to decline to answer any question. At certain centers where this study is done, you may also have your eyes evaluated and be asked specific questions about the quality of your life before, during, and after the treatment. It is not clear now whether either of the proposed treatment plans will be any better than the other. Therefore, to remove as much as possible any bias or prejudice that one treatment plan is more effective than the other, if you agree to participate in this study, you will be assigned to one of the treatment groups by chance. The possibility of receiving either of the treatments will be chosen by a process called “randomization.” Randomization means that a statistical office or computer will assign you to one of the treatment groups by a process that is like flipping a coin. Your chance of being assigned to either group is about equal.
After the randomization, you will be given the treatment assigned to you:
Treatment A: If you are randomized to this treatment, you will receive Tamoxifen 20 mg given each day by mouth for five years.
Treatment B: If you are randomized to this treatment, you will receive Toremifene 60 mg given each day by mouth for five years.
If your surgery to remove your breast cancer was a partial mastectomy (called a “lumpectomy”) you may also have radiation therapy given to the breast where the tumor was removed. You may receive radiation and the hormone treatment at the same time.
RISKS AND DISCOMFORTS
Drugs used to treat cancer often have side effects. The treatments described in this program may cause all, some, or none of the side effects listed. In addition, there is always the risk of previously unknown side effects occurring. Should new side effects be reported, you will be informed. You will be monitored closely to see if any of these side effects are occurring. Your treatment plan may be changed depending on the side effects you experience. As a result the only thing that they would be able to then do for the next couple of days is gambling online as it poses no physical risks. Routine tests will be done to check the effects of your treatment, including physical examinations, pelvic examinations, and x-rays to check the status of your disease. Side effects usually disappear after the treatment is stopped. In the meantime, medication may be given to keep these side effects under control. Other side effects could be long-lasting or permanent. The use of medications to control side effects could result in added costs. This institution is not financially responsible for treatment of side effects caused by the therapy offered in this study. I understand that I, or my insurance company, will be responsible for these costs.
If you are pregnant, you cannot take part in this study. We do not know how these drugs affect an unborn child. Therefore, a pregnancy test may be necessary. A woman of child bearing age must be using a good method of birth control while on this study. These methods would include condoms, diaphragms or other barrier methods to prevent pregnancy as approved by your physician. If you become pregnant or suspect that you may be pregnant, you must tell your physician and our investigator immediately. It is possible that you may have to make a decision whether or not to terminate your pregnancy.
Common side effects of Tamoxifen include: hot flashes; nausea; vaginal bleeding; vaginal discharge and dryness; menstrual irregularities; skin rash. Other side effects rarely seen are: increase in calcium in the body; swelling in arms, legs, hands, and feet; loss of appetite; distaste for food; genital itching; depression; dizziness; headache; leg cramps; lightheadedness; hair thinning or partial hair loss; confusion; fatigue. In addition, there is a risk of myocardial infarction. There is also the possibility of developing endometrial cancer. A mild decrease in the white cells and increased risk of infection and platelets with increased risk of bruising or bleeding may occur temporarily. An increased risk of cataracts has been reported. Other eye problems, such as retinopathy and corneal changes have been reported in a few patients.
Tamoxifen should not be taken in pregnancy due to potential harm to the fetus. The drug may cause changes in the lining of the uterus (endometrium), including polyps, hyperplasia, and endometriosis (endometrial cells outside the uterus). Patients should report any vaginal bleeding or pelvic pain to their physician. The level of increased risk of uterine cancer is uncertain: after 8 years of follow-up on a large national study of breast cancer patients taking 20 mg of tamoxifen/day, the annual risk observed is about 2/1000 women. This means that on the average, 2 cases of endometrial cancer were diagnosed among every 1000 women receiving tamoxifen during each year of study participation and follow-up. This level of risk is about 3 times greater than that of a similar group of women in the general population. Uterine cancer is a potentially life-threatening illness. Some breast cancer patients who developed uterine cancer while taking tamoxifen have subsequently died from uterine cancer. However, most of the uterine cancers that have occurred have been diagnosed at an early stage when treatment is highly effective. The treatment for early-stage uterine cancer usually involves a hysterectomy (surgical removal of the uterus) as well as removal of the fallopian tubes and ovaries, and may include radiation therapy. In view of this risk, it is recommended that all women receiving tamoxifen have a gynecologic examination prior to starting treatment and at least yearly thereafter. If you have had a total hysterectomy, you are not at risk for endometrial cancer. Reports of rare cases of liver cancer occurring in women taking tamoxifen have been made. Although tamoxifen can cause liver cancer in rats, it is not known to be a cause of liver cancer in humans. Ovarian cysts have been seen in premenopausal women taking tamoxifen. A few cases of liver abnormalities have been reported, some of which resulted in death, but whether the cause of these problems was tamoxifen is uncertain. Women on tamoxifen have an increased risk of inflammation of the vein and blood clots; rarely death has occurred from such events. Patients with a previous history of such problems should discuss them with their physician prior to taking tamoxifen.
Common side effects of Toremifene include: hot flashes; sweating; nausea; vomiting; white, clear, or colored vaginal discharge; vaginal bleeding; dizziness; swelling of the hands, feet, ankles, or fingers. Less frequently reported were: pain, headache, back pain, chest pain, fatigue, inability to sleep, fever, numbness or tingling in fingers or toes, lack of appetite, changes in your menstrual cycle, hair loss, thirst, constipation, sleepiness, diarrhea, heartburn, skin discoloration, abdominal pain, and weight gain. Toremifene has been used for a limited amount of time. The following rare, but possible side effects have occurred while patients have been taking Toremifene: (DVT) deep vein thrombosis, (CVA) stroke, and endometrial cancer (cancer of the uterus). These may or may not be directly related to the use of Toremifene. As more patients are treated with this drug for longer periods of time, new side effects or side effects similar to those seen with Tamoxifen, may be reported. If other risks become known, they will be told to you.
Radiation Therapy: Radiation therapy is usually necessary for women treated for breast cancer who desire preservation of the breast. Radiation treatment most often is given once a day, 5 days/week, to the breast where the tumor was removed. The radiation oncologist will explain the exact schedule to be followed and the type of side effects that might be expected. Possible side effects include skin reaction (dryness, redness, or peeling of skin); decrease in blood counts; soreness on swallowing; inflammation of the lungs; rarely, cardiac problems. You will be checked closely to see if any of these side effects described above are occurring. Your treatment may be stopped temporarily or changed depending on whether side effects are occurring. If severe side effects occur, you may be taken off the study and alternative treatments or no further treatment will be discussed with you.
BENEFITS
It is not known if any benefit will be obtained from the treatments described in this study. Predicting whether either of these treatment plans will reduce the risk that your cancer will come back or spread is not possible. Should your cancer become worse, or side effects become very severe or new scientific developments occur that show the treatment is not in your best interest, or should your physician feel that this treatment is no longer in your best interest, the treatment would be stopped. Further treatment, or the option of no additional treatment, would be discussed.
ALTERNATIVES
Alternative treatments that could be considered in your case include treatment with drugs to relieve symptoms, treatment with radiation, other hormones, cancer chemotherapy drugs, other investigational therapy, or no treatment at all. Side effects from other therapies may be similar to or different from those associated with the treatment proposed in this study. Your doctor can provide detailed information about your disease and proposed therapy and the benefits of the various treatments available.
COSTS/COMPENSATION
You or your insurance company will be responsible for the costs of medical treatment for any research-related injury. The doctor will make available or arrange for care and treatment for any physical injury resulting from this study. The University of Louisville, Department of Surgery has not arranged for payment of costs associated with any injury resulting from being in this study.
You are volunteering to be in this study. No compensation for participation will be given. You or your insurance company will be responsible for the costs of hospitalization, surgical procedures, anesthesia, tests, clinic visits, doctors’ fees, and non-investigational drugs besides the costs of administering the drug treatment. The cost of standard treatment will be billed to you or your insurance company in the usual manner. The drugs tamoxifen and toremifene are commercially available and related costs will be billed to you or your insurance company. However, if you cannot find reimbursement through insurance or other avenues for Fareston or tamoxifen, The Franklin Group, Inc will provide support to identify possible sources of patient assistance.
CONFIDENTIALITY
Absolute confidentiality cannot be guaranteed. All data collected in this study will be held in confidence to the extent permitted by law. The results of this study may be published, but your name or your identity will not be revealed. A record of your progress while on the study will be kept in a confidential file. The confidentiality of the central computer record is carefully guarded. During their required reviews, representatives of the Food and Drug Administration (FDA), the National Cancer Institute (NCI), the manufacturers of the drugs, and the University of Louisville Department of Surgery may have access to the medical records that contain your identity. In addition, The University Human Studies Committee may also inspect your research records. However, no information by which you can be identified will be released or published. Pathology material, including slides, may be sent to a central office for review.
STATEMENT OF VOLUNTARY PARTICIPATION
Your participation in this study is voluntary. You understand that you have the right to ask questions anytime and to refuse to continue in the study if you so desire without penalties, loss of benefits, or loss of additional treatment. You understand that your regular doctor will answer any questions about your disease and its treatment and/or your participation in the study. You understand that by consenting to participate in this study, you are responsible for carrying out instructions and that you must report to your doctors, nurses, or other study personnel any information that might be pertinent to the study, such as any side effects of a treatment or procedure. Any reluctance you might have to continue in the study must also be reported. You have been guaranteed that any new information regarding the study and any treatment it involves which might affect your willingness to continue my participation in the study will be related to you in an appropriate way.
You or your insurance company will be responsible for the costs of hospitalization (if needed), tests, clinic visits, doctor’s fees, and non-investigational drugs in addition to the costs of administering the drug treatment. The costs of the drugs to be given that are commercially available and their administration, or your care related to the chemotherapy or radiation therapy, will not be provided as part of this study. All of your present questions have been answered in language you can understand. All future questions will be treated in the same manner. You have read all of the above, asked questions, received answers concerning things you did not understand, and willingly give your consent to participate in this study. Upon signing this form you will receive a copy.
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