Phase II study of celecoxib in metastatic differentiated thyroid carcinoma.

CONTEXT: There is increased cyclooxygenase-2 (COX-2) expression in malignant thyroid nodules compared with nonneoplastic and benign thyroid tissue. OBJECTIVE: The objective of the study was to evaluate the efficacy of celecoxib, a selective COX-2 inhibitor, in treating patients with progressive metastatic differentiated thyroid cancer (DTC) and to explore the relationship of clinical response to tumor COX-2 expression with immunohistochemistry in a subset of patients. DESIGN: The study was a prospective phase II trial with Fleming single-stage design powered at 80% with a 5% rejection error to detect more than 20% progression-free survival at 12 months. SETTING: Ambulatory patients were from tertiary referral academic medical centers. PATIENTS: Patients in the study had progressive metastatic DTC and had failed prior standard therapy. INTERVENTION: Patients were treated with celecoxib 400 mg orally twice a day for 12 months. MAIN OUTCOME MEASURE: The main outcome measure was progression-free survival at 12 months of treatment using Response Evaluation Criteria in Solid Tumors and/or serum thyroglobulin. RESULTS: Twenty-three of 32 patients experienced progressive disease or stopped therapy due to toxicity, thus fulfilling the intent-to-treat study endpoint for celecoxib failure. One patient achieved partial response, and one patient completed 12 months of therapy progression-free. The patient with partial response was on therapy along with seven other patients when the study was terminated. CONCLUSIONS: Celecoxib 400 mg orally twice per day fails to halt progressive metastatic DTC in most patients.

Breast cancer: relationship between menopausal symptoms, physiologic health effects of cancer treatment and physical constraints on quality of life in long-term survivors.

AIMS AND OBJECTIVES: The purpose of this study is to describe the relationship between menopausal symptoms, physiologic health effects of cancer treatment and the physical contributors to quality of life in long-term survivors of breast cancer. BACKGROUND: The treatment of menopausal symptoms is hotly debated, especially for women with breast cancer. Common treatments for menopausal symptoms are considered to be contraindicated in women with breast cancer. DESIGN: This is a descriptive, cross-sectional study of long-term breast cancer survivors; a subset of a study that responded to a mailed survey targeting long-term cancer survivors treated at The University of Texas M.D. Anderson Cancer Center. METHODS: In 291 breast cancer patients information was available that included items that commonly relate to menopausal symptoms including hot flushes, painful sexual intercourse, inability to concentrate, fatigue and sleep disturbances. RESULTS: Ninety per cent were Caucasian American and the mean time since diagnosis was 16 +/- 8 years. All patients had been treated with surgery, (60%) with radiotherapy, (68%) with chemotherapy and (37%) with hormonal therapy. Forty-six per cent of the breast cancer survivors indicated that having breast cancer affected their overall health. Self-reported health effects were more common in those survivors who had received a combination of chemotherapy and radiotherapy. A menopausal quality of life score was determined using the items about hot flushes, ability to concentrate, painful sexual intercourse, fatigue, unhappiness and sleep disturbances. CONCLUSIONS: This study reminds us that breast cancer and menopause are independent issues. Quality of life parameters need to be rigidly defined and time sensitive. There are complex interactions between quality of life indicators and specific physiologic consequences of treatment. However, menopausal signs and symptoms may not be different for the breast cancer survivor and they should not be confused with the quality of life/psychosocial issues of the cancer survivor. RELEVANCE TO CLINICAL PRACTICE: Menopause is not a disease process but a normal developmental stage for women. It is important for nurses not only to understand the client needs of the menopausal woman, but also to be able to differentiate between quality of life issues related to menopause and to cancer treatment in order to provide holistic nursing care.

Health care priorities for menopausal women with a history of breast cancer.

BACKGROUND: The opinion of breast cancer survivors and their physicians about long-term health, especially menopause, is not well understood. METHODS: Seventy-three patients and 22 physicians answered questions regarding medical follow-up and menopause. RESULTS: One third of specialists preferred follow-up of 5 years or less, while 59% preferred 10 years or longer; 46% of patients preferred follow-up for 10 years or longer. Physicians preferred that primary care physicians supervise menopausal health (55%), but patients disagreed (30%). Physicians cited heart health most important, followed by skeletal health and climacteric symptoms. Physicians believed that climacteric symptoms were patients' leading concern, but patients cited heart health, followed by skeletal health and cognitive dysfunction. Neither patients nor physicians advocated estrogen use. CONCLUSIONS: Differences of opinion exist between breast cancer patients and specialists regarding follow-up and management of menopause. However, both patients and physicians prefer prolonged surveillance by a cancer specialist, with attention to heart and skeletal health issues.

Estrogen replacement therapy for menopausal women with a history of breast carcinoma: results of a 5-year, prospective study.

BACKGROUND: Women with a history of breast carcinoma generally have been advised to avoid estrogen replacement therapy (ERT). The validity of this approach has been scrutinized and debated in recent years, and reassessment through appropriate clinical trials has been suggested. METHODS: The authors conducted a prospective clinical trial to assess the safety and efficacy of prolonged ERT in a group of menopausal women with localized (Stage I or Stage II) breast carcinoma and a minimum disease free interval of 2 years if estrogen receptor (ER) was negative or 10 years if ER status was unknown. For 5 years, the authors followed 77 trial participants and 222 other women with clinical and prognostic characteristics comparable to those of the trial participants. Overall, 56 women were on ERT, and 243 women were not on ERT. The association of ERT with skeletal and lipid changes was assessed in the randomized trial participants. The effect of ERT on the development of recurrent or new breast carcinoma and other carcinomas was analyzed both in the trial participants and in the overall group. RESULTS: Patient and disease characteristics, such as tumor size, number of lymph nodes involved, ER status, menopausal status, and disease free interval were comparable for women who were on ERT and women who were not on ERT. These same parameters also were comparable for women who joined the trial and women who did not. ERT use was associated with modest lipid and skeletal benefits. The introduction of ERT did not compromise disease free survival. Two of 56 women on ERT (3.6%) developed a contralateral, new breast carcinoma. In the group that was not on ERT, 33 of 243 women (13.5%) developed new or recurrent breast carcinoma. There were no differences in the development of other carcinomas with respect to ERT. CONCLUSIONS: ERT did not compromise disease free survival in select patients who were treated previously for localized breast carcinoma. Larger scale randomized trials are needed to confirm these findings.